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Evaluating the Safety of Immediate Versus Deferred Isoniazid Preventive Therapy Among HIV-Infected Pregnant Women

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01494038
Recruitment Status : Completed
First Posted : December 16, 2011
Results First Posted : November 20, 2018
Last Update Posted : November 20, 2018
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Care Provider);   Primary Purpose: Prevention
Conditions HIV Infections
Tuberculosis
Interventions Drug: Isoniazid (INH)
Drug: Placebo for isoniazid (INH)
Enrollment 956
Recruitment Details HIV-infected pregnant women and their infants, gestational age greater than 14 but less than 34 weeks, who reside in a high TB prevalence area. Recruited at participating medical clinics in those areas, a total of 13 sites in Haiti, India, Thailand, and in 5 countries in central and southern Africa. Recruitment from August 2014 to April 2016.
Pre-assignment Details  
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit

Period Title: Overall Study
Started 477 479
Completed 389 396
Not Completed 88 83
Reason Not Completed
Protocol Violation             1             1
Lost to Follow-up             18             20
Withdrawal by Subject             44             34
Not able to get to clinic             21             15
Not willing to adhere to reqs             2             9
Death             2             4
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment) Total
Hide Arm/Group Description

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum (Arm B)

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit (Arm B)

Total of all reporting groups
Overall Number of Baseline Participants 477 479 956
Hide Baseline Analysis Population Description
All women in study.
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 477 participants 479 participants 956 participants
29
(25 to 33)
29
(24 to 33)
29
(24 to 33)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 477 participants 479 participants 956 participants
Female
477
 100.0%
479
 100.0%
956
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 477 participants 479 participants 956 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
32
   6.7%
35
   7.3%
67
   7.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
445
  93.3%
444
  92.7%
889
  93.0%
White
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Haiti Number Analyzed 477 participants 479 participants 956 participants
8 15 23
Botswana Number Analyzed 477 participants 479 participants 956 participants
60 60 120
Tanzania Number Analyzed 477 participants 479 participants 956 participants
41 39 80
South Africa Number Analyzed 477 participants 479 participants 956 participants
91 91 182
Uganda Number Analyzed 477 participants 479 participants 956 participants
83 83 166
Zimbabwe Number Analyzed 477 participants 479 participants 956 participants
162 157 319
Thailand Number Analyzed 477 participants 479 participants 956 participants
15 18 33
India Number Analyzed 477 participants 479 participants 956 participants
17 16 33
Gestational age at entry  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 477 participants 479 participants 956 participants
14 - <24 weeks
161
  33.8%
160
  33.4%
321
  33.6%
24 - 34 weeks
316
  66.2%
319
  66.6%
635
  66.4%
CD4 Count   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 475 participants 477 participants 952 participants
< 350 cells/mm^3
118
  24.8%
114
  23.9%
232
  24.4%
350 - <500 cells/mm^3
129
  27.2%
128
  26.8%
257
  27.0%
500 - <650 cells/mm^3
95
  20.0%
105
  22.0%
200
  21.0%
>= 650 cells/mm^3
133
  28.0%
130
  27.3%
263
  27.6%
[1]
Measure Analysis Population Description: N=4 participants did not have baseline CD4 result available.
Efavirenz-containing anti-retroviral (ARV) regimen  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 477 participants 479 participants 956 participants
No
72
  15.1%
70
  14.6%
142
  14.9%
Yes
405
  84.9%
409
  85.4%
814
  85.1%
Tuberculosis (TB) test result by Interferon-Gamma Release Assay (IGRA)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 470 participants 472 participants 942 participants
Positive
139
  29.6%
144
  30.5%
283
  30.0%
Negative
301
  64.0%
297
  62.9%
598
  63.5%
Indeterminate
30
   6.4%
31
   6.6%
61
   6.5%
[1]
Measure Analysis Population Description: All enrolled participants with IGRA results available
1.Primary Outcome
Title Incidence Rate of Combined Endpoint: Grade 3 or Higher Adverse Events (AEs) Related to Treatment, or AE Causing Discontinuation of Treatment
Hide Description Incidence rate, calculated by Mantel-Haenszel (MH), weighted by gestational age strata 1) gestational age at entry less than 24 weeks or 2) gestational age at entry greater than or equal to 24 weeks. AE's include laboratory results, signs/symptoms, or diagnoses; graded as per Division of AIDS (DAIDS) or by protocol-defined hepatotoxicity measures. Related to treatment indicates possibly, probably, or definitely related to INH or Placebo for INH as judged by Independent Endpoint Review Committee. Discontinuation refers to permanent discontinuation of study treatment.
Time Frame Measured from study entry through Week 48 after birth
Hide Outcome Measure Data
Hide Analysis Population Description
All women enrolled.
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 477 479
Measure Type: Number
Unit of Measure: events per 100 person-years
15.03 14.93
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Calculate the difference between the immediate arm incidence rate and the deferred arm incidence rate; if the upper bound of the 95% confidence interval is lower than a 5% difference in incidence rates, non-inferiority will be considered to be proven.
Method of Estimation Estimation Parameter Incidence rate difference
Estimated Value 0.10
Confidence Interval (2-Sided) 95%
-4.77 to 4.98
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Number of Mothers With a Fetal Death
Hide Description Fetal deaths include both stillbirths and spontaneous abortions; in case of a multiple birth, mothers who had at least one fetal death
Time Frame Measured from study entry through end of pregnancy
Hide Outcome Measure Data
Hide Analysis Population Description
Mothers who had at least one live birth, stillbirth, or spontaneous abortion. One participant with outcome of induced abortion not included
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 459 466
Measure Type: Count of Participants
Unit of Measure: Participants
17
   3.7%
9
   1.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.093
Comments [Not Specified]
Method Fisher Exact
Comments mid-P adjustment
3.Secondary Outcome
Title Number of Mothers With a Fetus Small for Gestational Age
Hide Description Small for gestational age was determined by physician at site
Time Frame Measured at delivery
Hide Outcome Measure Data
Hide Analysis Population Description
Measurement of small-for-gestational-age was deemed to be unreliable. Analysis not performed.
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Number of Mothers With an Infant Born Prematurely
Hide Description Premature birth is defined as gestational age of < 37 weeks at delivery.
Time Frame Measured at delivery
Hide Outcome Measure Data
Hide Analysis Population Description
Mothers who had at least one live birth
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 442 458
Measure Type: Count of Participants
Unit of Measure: Participants
48
  10.9%
40
   8.7%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.288
Comments [Not Specified]
Method Fisher Exact
Comments mid-P adjustment
5.Secondary Outcome
Title Number of Mothers With a Low Birth-weight Infant
Hide Description Low birth weight is defined as weight < 2500 mg
Time Frame Measured on day of birth
Hide Outcome Measure Data
Hide Analysis Population Description
Mothers who had at least one live birth available to be weighed at time of delivery
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 430 446
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
62
  14.4%
46
  10.3%
No
368
  85.6%
400
  89.7%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.073
Comments [Not Specified]
Method Fisher Exact
Comments mid-P adjustment
6.Secondary Outcome
Title Number of Mothers With an Infant With a Congenital Anomaly
Hide Description Includes congenital anomalies meeting the Metropolitan Atlanta Congenital Defects Program criteria.
Time Frame Measured from study entry through Week 48 after birth
Hide Outcome Measure Data
Hide Analysis Population Description
Mothers who had at least one live birth able to be assessed between birth and 48 weeks after birth
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 440 458
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
10
   2.3%
6
   1.3%
No
430
  97.7%
452
  98.7%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.264
Comments [Not Specified]
Method Fisher Exact
Comments mid-P adjustment
7.Secondary Outcome
Title Number of Mothers With an Adverse Pregnancy Outcome: Spontaneous Abortion, Stillbirth, Premature Birth, Low Birth Weight, or Congenital Anomaly
Hide Description In case of a multiple birth, mothers who had at least one adverse pregnancy outcome. Spontaneous abortion is intra-uterine fetal death prior to 20 weeks of gestational age; stillbirth, the same, >= 20 weeks; preterm delivery, < 37 weeks of gestational age; low birth weight, < 2,500 grams, and congenital anomalies meeting the Metropolitan Atlanta Congenital Defects Program criteria.
Time Frame Measured from study entry through Week 48 after birth
Hide Outcome Measure Data
Hide Analysis Population Description
Mothers who had at least one live birth, stillbirth, or spontaneous abortion; participant with induced abortion is omitted, and whose babies were available for examination after birth (if born alive)
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit

Overall Number of Participants Analyzed 449 460
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
106
  23.6%
78
  17.0%
No
343
  76.4%
382
  83.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments [Not Specified]
Method Fisher Exact
Comments Mid-P adjustment
8.Secondary Outcome
Title Number of Infants With Grade 3 or Higher Clinical or Laboratory AE
Hide Description Laboratory, sign/symptom, or diagnoses graded as 3 or higher by DAIDS criteria.
Time Frame Measured from study entry through Week 48 after birth
Hide Outcome Measure Data
Hide Analysis Population Description
Infants born alive
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 445 464
Measure Type: Count of Participants
Unit of Measure: Participants
193
  43.4%
196
  42.2%
9.Secondary Outcome
Title Number of Infants With Grade 3 or Higher Clinical or Laboratory AE Related to Treatment
Hide Description As before, but AE is judged to be possibly, probably, or definitely related to INH or Placebo for INH, by clinic medical staff
Time Frame Measured from study entry through Week 48 after birth
Hide Outcome Measure Data
Hide Analysis Population Description
Infants born alive
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 445 464
Measure Type: Count of Participants
Unit of Measure: Participants
5
   1.1%
6
   1.3%
10.Secondary Outcome
Title Number of Infants Which Are HIV-infected
Hide Description HIV infection determined during follow-up period. Infection at birth or during breastfeeding
Time Frame Measured from study entry through study Week 44
Hide Outcome Measure Data
Hide Analysis Population Description
Infants born alive
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 445 464
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
3
   0.7%
7
   1.5%
No
436
  98.0%
451
  97.2%
Unknown
6
   1.3%
6
   1.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.279
Comments [Not Specified]
Method Fisher Exact
Comments mid-P adjustment
11.Secondary Outcome
Title Number of Infants Hospitalized
Hide Description Hospitalization due to reasons other than birth
Time Frame Measured from study entry through Week 48 after birth
Hide Outcome Measure Data
Hide Analysis Population Description
Infants born alive
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 445 464
Measure Type: Count of Participants
Unit of Measure: Participants
73
  16.4%
75
  16.2%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .893
Comments [Not Specified]
Method Fisher Exact
Comments mid-P adjustment
12.Secondary Outcome
Title Incidence Rate of TB Infection Among Mothers
Hide Description Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata. Probable or confirmed TB infection, as judged by Secondary Endpoint Review Committee
Time Frame Measured from study entry to Week 48 after birth
Hide Outcome Measure Data
Hide Analysis Population Description
All participants enrolled without active TB at entry
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 477 478
Measure Type: Number
Unit of Measure: events per 100 person-years
0.60 0.59
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Incidence rate difference
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-0.94 to 0.96
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Incidence Rate of Tuberculosis (TB) Among Infants
Hide Description Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata. Probable or confirmed TB, or congenital TB as defined using the Cantwell criteria (see reference), judged by the Secondary Endpoint Review Committee. Includes an infant death due to unknown cause.
Time Frame Measured from study entry through Week 48 after birth
Hide Outcome Measure Data
Hide Analysis Population Description
Live-born infants of enrolled women
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 445 464
Measure Type: Number
Unit of Measure: events per 100 person-years
0.54 0.52
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Incidence rate difference
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-1.02 to 1.07
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Incidence Rate of Infant Death
Hide Description Incidence rate was calculated by Mantel-Haenszel, weighted by gestational age strata.
Time Frame Measured from study entry through Week 48 after birth
Hide Outcome Measure Data
Hide Analysis Population Description
Live-born infants of enrolled women
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 445 464
Measure Type: Number
Unit of Measure: events per 100 person-years
2.99 4.42
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Incidence rate difference
Estimated Value -1.43
Confidence Interval (2-Sided) 95%
-4.17 to 1.32
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Incidence Rate of Maternal Deaths
Hide Description Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata.
Time Frame Measured from study entry through Week 48 postpartum
Hide Outcome Measure Data
Hide Analysis Population Description
All participants enrolled without active TB at entry
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 477 478
Measure Type: Number
Unit of Measure: events per 100 person-years
0.40 0.78
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Incidence rate difference
Estimated Value -0.39
Confidence Interval (2-Sided) 95%
-1.33 to 0.56
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Incidence Rate of Combined Endpoints: Maternal TB or Maternal Death
Hide Description Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata.
Time Frame Measured from study entry through Week 48 after birth
Hide Outcome Measure Data
Hide Analysis Population Description
All participants enrolled without active TB at entry.
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 477 478
Measure Type: Number
Unit of Measure: events per 100 person-years
1.00 1.38
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Incidence rate difference
Estimated Value -0.38
Confidence Interval (2-Sided) 95%
-1.72 to 0.97
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Incidence Rate of Combined Endpoints: Infant TB or Infant Death
Hide Description Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata.
Time Frame Measured from study entry through Week 48 after birth
Hide Outcome Measure Data
Hide Analysis Population Description
Live-born infants of enrolled women
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 445 464
Measure Type: Number
Unit of Measure: events per 100 person-years
2.99 4.68
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Incidence rate difference
Estimated Value -1.69
Confidence Interval (2-Sided) 95%
-4.48 to 1.1
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Incidence Rate of Combined Endpoints: Maternal TB, Maternal Death, Infant TB, or Infant Death
Hide Description Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata.
Time Frame Measured from study entry through Week 48 after birth
Hide Outcome Measure Data
Hide Analysis Population Description
Number of mother-infant pairs with at least one infant live birth and in which mother did not have active TB at entry.
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 442 458
Measure Type: Number
Unit of Measure: events per 100 person-years
3.42 4.72
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Incidence rate difference
Estimated Value -1.30
Confidence Interval (2-Sided) 95%
-3.86 to 1.25
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Incidence Rate of Combined Endpoint, Antepartum: Grade 3 or Higher AE Related to Treatment, or Discontinuation of Treatment Due to AE
Hide Description Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata
Time Frame Measured from study entry through end of pregnancy
Hide Outcome Measure Data
Hide Analysis Population Description
All women enrolled.
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 477 479
Measure Type: Number
Unit of Measure: events per 100 person-years
15.93 13.79
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Incidence rate difference
Estimated Value 2.14
Confidence Interval (2-Sided) 95%
-7.86 to 12.13
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Incidence Rate of Combined Endpoint, up to 12 Weeks Postpartum: Grade 3 or Higher AE Related to Treatment, or Discontinuation of Treatment Due to AE
Hide Description Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata.
Time Frame Measured from study entry through 12 weeks after birth
Hide Outcome Measure Data
Hide Analysis Population Description
All women enrolled.
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 477 479
Measure Type: Number
Unit of Measure: events per 100 person-years
16.98 10.09
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Incidence rate difference
Estimated Value 6.89
Confidence Interval (2-Sided) 95%
-0.08 to 13.86
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Incidence Rate, Antepartum, of Grade 3 or Higher AE
Hide Description Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata.
Time Frame Measured from study entry through end of pregnancy
Hide Outcome Measure Data
Hide Analysis Population Description
All women enrolled.
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 477 479
Measure Type: Number
Unit of Measure: events per 100 person-years
56.36 50.88
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Incidence rate difference
Estimated Value 5.49
Confidence Interval (2-Sided) 95%
-13.7 to 24.68
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Incidence Rate, up to 12 Weeks Postpartum, of Grade 3 or Higher AE
Hide Description Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata.
Time Frame Measured from study entry through 12 weeks postpartum
Hide Outcome Measure Data
Hide Analysis Population Description
All women enrolled.
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 477 479
Measure Type: Number
Unit of Measure: events per 100 person-years
56.48 40.59
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Incidence rate difference
Estimated Value 15.88
Confidence Interval (2-Sided) 95%
2.11 to 29.65
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Incidence Rate, Antepartum, of Hepatotoxicity, Defined by Protocol-specific Definition of Hepatotoxicity, Related to Treatment
Hide Description Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata. Protocol-specific definition of hepatotoxicity: Any one of the following: 1) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 5 times the upper limit of normal (ULN), where ULN is specified by the clinic physician; 2) Total bilirubin > 3 X ULN; 3) ALT greater than 3 X ULN and total bilirubin greater than 2 X ULN; or 4) ALT > 3 X ULN and persistent symptomatic clinical hepatitis
Time Frame Measured from study entry through delivery
Hide Outcome Measure Data
Hide Analysis Population Description
All women enrolled.
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 477 479
Measure Type: Number
Unit of Measure: events per 100 person-years
1.77 2.59
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Incidence rate difference
Estimated Value -0.82
Confidence Interval (2-Sided) 95%
-4.63 to 3
Estimation Comments [Not Specified]
24.Secondary Outcome
Title Incidence Rate, to 12 Weeks Postpartum, of Hepatotoxicity, Protocol-specific Definition, Related to Treatment
Hide Description Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata
Time Frame Measured from study entry through 12 weeks postpartum
Hide Outcome Measure Data
Hide Analysis Population Description
All women enrolled.
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit

Overall Number of Participants Analyzed 477 479
Measure Type: Number
Unit of Measure: events per 100 person-years
7.91 4.52
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Incidence rate difference
Estimated Value 3.38
Confidence Interval (2-Sided) 95%
-1.31 to 8.07
Estimation Comments [Not Specified]
25.Secondary Outcome
Title Incidence Rate, Antepartum, of Hepatotoxicity, Protocol-specific Definition, Any Cause
Hide Description Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata.
Time Frame Measured from study entry through delivery
Hide Outcome Measure Data
Hide Analysis Population Description
All women enrolled.
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 477 479
Measure Type: Number
Unit of Measure: events per 100 person-years
1.77 2.59
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Incidence rate difference
Estimated Value -0.82
Confidence Interval (2-Sided) 95%
-4.63 to 3
Estimation Comments [Not Specified]
26.Secondary Outcome
Title Incidence Rate, to 12 Weeks Postpartum, of Hepatotoxicity, Protocol-specific Definition, Any Cause
Hide Description Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata.
Time Frame Measured from study entry through 12 weeks postpartum
Hide Outcome Measure Data
Hide Analysis Population Description
All women enrolled
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 477 479
Measure Type: Number
Unit of Measure: events per 100 person-years
8.37 4.98
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Incidence rate difference
Estimated Value 3.39
Confidence Interval (2-Sided) 95%
-1.46 to 8.25
Estimation Comments [Not Specified]
27.Secondary Outcome
Title Incidence Rate, Antepartum, of Hepatotoxicity, Defined by DAIDS, Related to Treatment
Hide Description Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata. Hepatotoxicity definition as defined by DAIDS AE grading criteria 1.0.
Time Frame Measured from study entry through delivery
Hide Outcome Measure Data
Hide Analysis Population Description
All women.
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 477 479
Measure Type: Number
Unit of Measure: events per 100 person-years
1.77 2.59
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Incidence rate difference
Estimated Value -0.82
Confidence Interval (2-Sided) 95%
-4.63 to 3
Estimation Comments [Not Specified]
28.Secondary Outcome
Title Incidence Rate, up to 12 Weeks Postpartum, of Hepatotoxicity, Defined by DAIDS, Related to Treatment
Hide Description Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata
Time Frame Measured from study start through 12 weeks postpartum
Hide Outcome Measure Data
Hide Analysis Population Description
All women
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 477 479
Measure Type: Number
Unit of Measure: events per 100 person-years
7.91 4.52
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Incidence rate difference
Estimated Value 3.38
Confidence Interval (2-Sided) 95%
-1.31 to 8.07
Estimation Comments [Not Specified]
29.Secondary Outcome
Title Incidence Rate, Antepartum, of Hepatotoxicity, Defined by DAIDS, Any Cause
Hide Description Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata.
Time Frame Measured from study entry through delivery
Hide Outcome Measure Data
Hide Analysis Population Description
All women
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 477 479
Measure Type: Number
Unit of Measure: events per 100 person-years
1.77 2.59
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Incidence rate difference
Estimated Value -0.82
Confidence Interval (2-Sided) 95%
-4.63 to 3
Estimation Comments [Not Specified]
30.Secondary Outcome
Title Incidence Rate, up to 12 Weeks Postpartum, of Hepatotoxicity, Defined by DAIDS, Any Cause
Hide Description Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata.
Time Frame Measured from study start through 12 weeks postpartum
Hide Outcome Measure Data
Hide Analysis Population Description
All women.
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 477 479
Measure Type: Number
Unit of Measure: events per 100 person-years
8.37 4.98
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Immediate INH Treatment), Arm B (Deferred INH Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Incidence rate difference
Estimated Value 3.39
Confidence Interval (2-Sided) 95%
-1.46 to 8.25
Estimation Comments [Not Specified]
31.Secondary Outcome
Title Number of Mothers With Tuberculosis Resistant to INH
Hide Description Resistance to INH from isolates of Mycobacterium tuberculosis, as a percentage of mothers who develop culture-confirmed TB
Time Frame Measured from study entry through Week 48 postpartum
Hide Outcome Measure Data
Hide Analysis Population Description
Mothers with culture-confirmed TB
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 2 2
Measure Type: Count of Participants
Unit of Measure: Participants
1
  50.0%
0
   0.0%
32.Secondary Outcome
Title Number of Infants With Tuberculosis Resistant to INH
Hide Description Resistance to INH from isolates of Mycobacterium tuberculosis, as a percentage of infants who develop culture-confirmed TB
Time Frame Measured from study entry through Week 48 after birth
Hide Outcome Measure Data
Hide Analysis Population Description
No infants had culture-confirmed TB
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
33.Secondary Outcome
Title Pharmacokinetic (PK) Parameter: Adjusted Mean of Area Under the Curve of Plasma Concentration Versus Time (AUC24h), for INH
Hide Description Pharmacokinetic parameter was estimated from population PK modeling fitted to the intensive PK data. AUC0-24h was predicted using population pharmacokinetic model using the NONMEM software program. A 2-compartment model with first-order absorption with transit compartment and first-order elimination with well-stirred liver model to capture hepatic clearance and first-pass extraction with 1 parameter (hepatic intrinsic clearance) was used,
Time Frame Measured at antepartum (third trimester and >= 2 weeks after starting study drug) and week 16 postpartum (+/-) 4 weeks) while on active INH; blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dosing.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with intensive pharmacokinetic results while on active INH, who were established on INH.
Arm/Group Title Fast Metabolizers Intermediate Metabolizers Slow Metabolizers
Hide Arm/Group Description:
Those women having a genotype of fast INH metabolism.
Those women having a genotype of intermediate INH metabolism.
Those women having a genotype of slow INH metabolism.
Overall Number of Participants Analyzed 5 15 12
Mean (95% Confidence Interval)
Unit of Measure: hour*mg/L
Third trimester of pregnancy
3.63
(2.88 to 4.88)
6.55
(5.31 to 7.88)
21.6
(18.5 to 26.0)
Week 16 postpartum
4.25
(3.29 to 5.54)
7.67
(6.49 to 9.18)
25.3
(22.2 to 26.0)
34.Secondary Outcome
Title Pharmacokinetic (PK) Parameter: Adjusted Mean of Area Under the Curve (AUC24h), for EFV
Hide Description Pharmacokinetic parameter was estimated from population PK modeling fitted to the intensive PK data. AUC0-24h was predicted using population pharmacokinetic model using the NONMEM software program. A 2-compartment model with first-order absorption with transit compartment and first-order elimination with well-stirred liver model to capture hepatic clearance and first-pass extraction with 1 parameter (hepatic intrinsic clearance) was used,
Time Frame Measured at antepartum (third trimester and >= 2 weeks after starting study drug) and week 16 postpartum (+/-) 4 weeks) while on active INH; blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dosing.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with intensive pharmacokinetic results while on active EFV and who were stabled on EFV-based ART.
Arm/Group Title Fast Metabolizers Intermediate Metabolizers Slow Metabolizers
Hide Arm/Group Description:
Those women with a phenotype of fast EFV metabolism.
Those women with a phenotype of intermediate EFV metabolism.
Those women with a phenotype of slow EFV metabolism.
Overall Number of Participants Analyzed 3 10 8
Mean (95% Confidence Interval)
Unit of Measure: hour*mg/L
Third trimester of pregnancy
38.5
(33.4 to 47.6)
62.5
(51.4 to 94.9)
153.02
(140.21 to 167)
Week 16 postpartum
46.9
(42.1 to 59.7)
76.2
(61.1 to 111)
186
(166 to 210)
35.Secondary Outcome
Title Agreement Between Interferon-gamma Release Assay (IGRA) TB Test and Tuberculin Skin Test (TST) Results, Women at Delivery
Hide Description IGRA done by Quantiferon Gold Test (QGIT). For women, TST is considered positive if greater than or equal to 5 mm
Time Frame Measured at delivery
Hide Outcome Measure Data
Hide Analysis Population Description
Women tested for tuberculosis infection at delivery
Arm/Group Title Positive IGRA TB Test Negative IGRA TB Test
Hide Arm/Group Description:
Women who had positive IGRA TB test at delivery
Women who had negative IGRA TB test at delivery
Overall Number of Participants Analyzed 208 517
Measure Type: Count of Participants
Unit of Measure: Participants
Positive tuberculin skin test
87
  41.8%
27
   5.2%
Negative tuberculin skin test
121
  58.2%
490
  94.8%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Positive IGRA TB Test, Negative IGRA TB Test
Comments [Not Specified]
Type of Statistical Test Other
Comments Measuring agreement between the tests
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Chi-squared
Comments McNemars test
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Positive IGRA TB Test, Negative IGRA TB Test
Comments [Not Specified]
Type of Statistical Test Other
Comments Agreement between tests
Method of Estimation Estimation Parameter Kappa coefficient
Estimated Value 0.42
Confidence Interval (2-Sided) 95%
0.35 to 0.50
Estimation Comments [Not Specified]
36.Secondary Outcome
Title Agreement Between IGRA and TST TB Test Results, Infant
Hide Description The TST result was positive if greater than or equal to 10 mm in HIV-negative infants, or greater than or equal to 5 mm in HIV-positive infants.
Time Frame Measured at week 44 after birth
Hide Outcome Measure Data
Hide Analysis Population Description
Infants with tuberculin tests performed at week 44 postpartum
Arm/Group Title Positive IGRA Test Negative IGRA Tuberculin Test
Hide Arm/Group Description:
Infants with positive IGRA test at week 44 postpartum
Infants with a negative IGRA test at 44 weeks postpartum
Overall Number of Participants Analyzed 42 642
Measure Type: Count of Participants
Unit of Measure: Participants
Positive tuberculin skin test
8
  19.0%
45
   7.0%
Negative tuberculin skin test
34
  81.0%
597
  93.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Positive IGRA Test, Negative IGRA Tuberculin Test
Comments [Not Specified]
Type of Statistical Test Other
Comments Agreement between tests
Statistical Test of Hypothesis P-Value 0.22
Comments [Not Specified]
Method Chi-squared
Comments McNemar's test
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Positive IGRA Test, Negative IGRA Tuberculin Test
Comments [Not Specified]
Type of Statistical Test Other
Comments Agreement between tests
Method of Estimation Estimation Parameter Kappa coefficient
Estimated Value 0.11
Confidence Interval (2-Sided) 95%
0.001 to 0.21
Estimation Comments [Not Specified]
37.Secondary Outcome
Title Agreement Between IGRA and TST TB Tests, Women at 44 Weeks Postpartum
Hide Description IGRA done by Quantiferon Gold Test (QGIT). For women, TST is considered positive if greater than or equal to 5 mm
Time Frame Measured at Week 44 postpartum
Hide Outcome Measure Data
Hide Analysis Population Description
Women who were tested for tuberculosis infection at 44 weeks postpartum
Arm/Group Title Positive IGRA TB Test Negative IGRA TB Test
Hide Arm/Group Description:
Women who had positive IGRA TB test at 44 weeks postpartum
Women who had negative IGRA TB test at 44 weeks postpartum
Overall Number of Participants Analyzed 227 479
Measure Type: Count of Participants
Unit of Measure: Participants
Positive tuberculin skin test
100
  44.1%
20
   4.2%
Negative tuberculin skin test
127
  55.9%
459
  95.8%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Positive IGRA TB Test, Negative IGRA TB Test
Comments [Not Specified]
Type of Statistical Test Other
Comments Agreement between tests
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Chi-squared
Comments McNemar's test
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Positive IGRA TB Test, Negative IGRA TB Test
Comments [Not Specified]
Type of Statistical Test Other
Comments Agreement between tests
Method of Estimation Estimation Parameter Kappa coefficient
Estimated Value 0.46
Confidence Interval (2-Sided) 95%
0.39 to 0.53
Estimation Comments [Not Specified]
38.Secondary Outcome
Title Number of Women by Level of Adherence to Prescribed Regimen, as Assessed by Self-report
Hide Description Adherence is the percentage of expected doses taken during the 28 week active treatment period, categorized as poor (<60%), reasonable (>= 60%, <80%), good (>=80%, <90%), or excellent (>= 90%). Measured by participant's self-report of doses taken within the last 3 days.
Time Frame Adherence reported every 4 weeks during active treatment; study entry through week 28 for Arm A, week 12 postpartum through week 40 postpartum for Arm B
Hide Outcome Measure Data
Hide Analysis Population Description
All women enrolled.
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit

Overall Number of Participants Analyzed 477 479
Measure Type: Count of Participants
Unit of Measure: Participants
Excellent adherence
400
  83.9%
363
  75.8%
Good adherence
47
   9.9%
35
   7.3%
Reasonable adherence
15
   3.1%
8
   1.7%
Poor adherence
4
   0.8%
7
   1.5%
Unknown
11
   2.3%
66
  13.8%
39.Secondary Outcome
Title Number of Women by Level of Adherence to Prescribed Regimen, as Assessed by Pill Count
Hide Description Adherence is the percentage of expected doses taken during the 28 week active treatment period. Pill count: participants returned their prescription pill containers, and the remaining (unused) pills were counted.
Time Frame Adherence reported every 4 weeks during active treatment; study entry through week 28 for Arm A, week 12 postpartum through week 40 postpartum for Arm B
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled women
Arm/Group Title Arm A (Immediate INH Treatment) Arm B (Deferred INH Treatment)
Hide Arm/Group Description:

Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from Week 12 postpartum through Week 40 postpartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit

Overall Number of Participants Analyzed 477 479
Measure Type: Count of Participants
Unit of Measure: Participants
Excellent adherence
408
  85.5%
376
  78.5%
Good adherence
42
   8.8%
28
   5.8%
Reasonable adherence
8
   1.7%
6
   1.3%
Poor adherence
5
   1.0%
3
   0.6%
Unknown
14
   2.9%
66
  13.8%
Time Frame From study entry to study completion at week 48 postpartum or premature study discontinuation
Adverse Event Reporting Description At entry, all diagnoses, signs/symptoms, and laboratory events were collected. Post-entry, all new diagnoses, signs/symptoms, or laboratory events of >= 3 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used. All eligible participants who initiated study treatment and their live-born infants are included.
 
Arm/Group Title Mother/Immediate INH Mother/Deferred INH Infant/Immediate INH Infant/Deferred INH
Hide Arm/Group Description

Women in Arm A received immediate, or antepartum-initiated, INH treatments. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by mouth, from entry through Week 28 antepartum

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from Week 28 visit through Week 40 postpartum.

Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.

Isoniazid (INH): 300-mg tablet once daily by month, from Week 12 postpartum through Week 40 postpartum.

Placebo for isoniazid (INH): Placebo tablet once daily by mouth, from entry until Week 12 postpartum visit.

Infants born alive to mothers on arm A (Immediate INH). Infants born alive to mothers on Arm B (Deferred INH).
All-Cause Mortality
Mother/Immediate INH Mother/Deferred INH Infant/Immediate INH Infant/Deferred INH
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/477 (0.42%)   4/479 (0.84%)   11/445 (2.47%)   17/464 (3.66%) 
Show Serious Adverse Events Hide Serious Adverse Events
Mother/Immediate INH Mother/Deferred INH Infant/Immediate INH Infant/Deferred INH
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   71/477 (14.88%)   69/479 (14.41%)   86/445 (19.33%)   91/464 (19.61%) 
Blood and lymphatic system disorders         
Anaemia  1  1/477 (0.21%)  2/479 (0.42%)  1/445 (0.22%)  0/464 (0.00%) 
Anaemia neonatal  1  0/477 (0.00%)  0/479 (0.00%)  0/445 (0.00%)  1/464 (0.22%) 
Anaemia of pregnancy  1  1/477 (0.21%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Haemorrhagic disease of newborn  1  0/477 (0.00%)  0/479 (0.00%)  2/445 (0.45%)  0/464 (0.00%) 
Iron deficiency anaemia  1  1/477 (0.21%)  0/479 (0.00%)  1/445 (0.22%)  0/464 (0.00%) 
Microcytic anaemia  1  0/477 (0.00%)  0/479 (0.00%)  0/445 (0.00%)  1/464 (0.22%) 
Thrombocytopenia  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  0/464 (0.00%) 
Cardiac disorders         
Mitral valve prolapse  1  0/477 (0.00%)  1/479 (0.21%)  0/445 (0.00%)  0/464 (0.00%) 
Congenital, familial and genetic disorders         
Atrial septal defect  1  0/477 (0.00%)  0/479 (0.00%)  0/445 (0.00%)  1/464 (0.22%) 
Choledochal cyst  1  1/477 (0.21%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Congenital cytomegalovirus infection  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  0/464 (0.00%) 
Congenital hydrocephalus  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  0/464 (0.00%) 
Congenital pneumonia  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  0/464 (0.00%) 
Congenital syphilis  1  0/477 (0.00%)  0/479 (0.00%)  2/445 (0.45%)  0/464 (0.00%) 
Dysmorphism  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  0/464 (0.00%) 
Exomphalos  1  0/477 (0.00%)  0/479 (0.00%)  0/445 (0.00%)  2/464 (0.43%) 
Patent ductus arteriosus  1  0/477 (0.00%)  0/479 (0.00%)  0/445 (0.00%)  2/464 (0.43%) 
Gastrointestinal disorders         
Abdominal pain  1  1/477 (0.21%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Abdominal pain lower  1  1/477 (0.21%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Diarrhoea  1  0/477 (0.00%)  1/479 (0.21%)  1/445 (0.22%)  1/464 (0.22%) 
Haemorrhoidal haemorrhage  1  1/477 (0.21%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Inguinal hernia  1  0/477 (0.00%)  0/479 (0.00%)  0/445 (0.00%)  1/464 (0.22%) 
Vomiting  1  0/477 (0.00%)  0/479 (0.00%)  0/445 (0.00%)  1/464 (0.22%) 
General disorders         
Death  1  0/477 (0.00%)  0/479 (0.00%)  2/445 (0.45%)  1/464 (0.22%) 
Fever neonatal  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  0/464 (0.00%) 
Macrosomia  1  0/477 (0.00%)  0/479 (0.00%)  0/445 (0.00%)  1/464 (0.22%) 
Pyrexia  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  3/464 (0.65%) 
Sudden infant death syndrome  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  1/464 (0.22%) 
Hepatobiliary disorders         
Drug-induced liver injury  1  2/477 (0.42%)  4/479 (0.84%)  1/445 (0.22%)  0/464 (0.00%) 
Hepatitis  1  0/477 (0.00%)  3/479 (0.63%)  0/445 (0.00%)  0/464 (0.00%) 
Hepatitis acute  1  1/477 (0.21%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Hepatotoxicity  1  1/477 (0.21%)  2/479 (0.42%)  0/445 (0.00%)  0/464 (0.00%) 
Immune system disorders         
Rhesus incompatibility  1  0/477 (0.00%)  0/479 (0.00%)  0/445 (0.00%)  1/464 (0.22%) 
Infections and infestations         
Acute sinusitis  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  0/464 (0.00%) 
Ascariasis  1  1/477 (0.21%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Breast abscess  1  0/477 (0.00%)  1/479 (0.21%)  0/445 (0.00%)  0/464 (0.00%) 
Bronchiolitis  1  0/477 (0.00%)  0/479 (0.00%)  3/445 (0.67%)  5/464 (1.08%) 
Bronchitis  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  0/464 (0.00%) 
Croup infectious  1  0/477 (0.00%)  0/479 (0.00%)  0/445 (0.00%)  1/464 (0.22%) 
Cryptosporidiosis infection  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  0/464 (0.00%) 
Diarrhoea infectious  1  0/477 (0.00%)  1/479 (0.21%)  0/445 (0.00%)  1/464 (0.22%) 
Diverticulitis  1  1/477 (0.21%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Endometritis  1  1/477 (0.21%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Enterococcal sepsis  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  0/464 (0.00%) 
Exanthema subitum  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  1/464 (0.22%) 
Gastroenteritis  1  1/477 (0.21%)  3/479 (0.63%)  3/445 (0.67%)  6/464 (1.29%) 
Gastroenteritis viral  1  0/477 (0.00%)  0/479 (0.00%)  0/445 (0.00%)  1/464 (0.22%) 
Genitourinary tract infection  1  1/477 (0.21%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Haemophilus sepsis  1  0/477 (0.00%)  0/479 (0.00%)  0/445 (0.00%)  1/464 (0.22%) 
Herpangina  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  0/464 (0.00%) 
Impetigo  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  0/464 (0.00%) 
Lower respiratory tract infection  1  0/477 (0.00%)  0/479 (0.00%)  0/445 (0.00%)  1/464 (0.22%) 
Meningitis  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  0/464 (0.00%) 
Oral candidiasis  1  0/477 (0.00%)  0/479 (0.00%)  0/445 (0.00%)  1/464 (0.22%) 
Parvovirus B19 infection  1  0/477 (0.00%)  0/479 (0.00%)  0/445 (0.00%)  1/464 (0.22%) 
Pharyngitis  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  0/464 (0.00%) 
Pneumonia  1  0/477 (0.00%)  1/479 (0.21%)  8/445 (1.80%)  10/464 (2.16%) 
Pneumonia bacterial  1  0/477 (0.00%)  1/479 (0.21%)  2/445 (0.45%)  4/464 (0.86%) 
Postoperative wound infection  1  0/477 (0.00%)  1/479 (0.21%)  0/445 (0.00%)  0/464 (0.00%) 
Postpartum sepsis  1  1/477 (0.21%)  2/479 (0.42%)  0/445 (0.00%)  0/464 (0.00%) 
Pulmonary tuberculosis  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  0/464 (0.00%) 
Respiratory syncytial virus bronchitis  1  0/477 (0.00%)  0/479 (0.00%)  0/445 (0.00%)  1/464 (0.22%) 
Sepsis  1  1/477 (0.21%)  0/479 (0.00%)  2/445 (0.45%)  2/464 (0.43%) 
Sepsis neonatal  1  0/477 (0.00%)  0/479 (0.00%)  11/445 (2.47%)  16/464 (3.45%) 
Upper respiratory tract infection  1  1/477 (0.21%)  0/479 (0.00%)  1/445 (0.22%)  1/464 (0.22%) 
Urinary tract infection  1  7/477 (1.47%)  5/479 (1.04%)  0/445 (0.00%)  0/464 (0.00%) 
Vaginal infection  1  0/477 (0.00%)  1/479 (0.21%)  0/445 (0.00%)  0/464 (0.00%) 
Viral rash  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  0/464 (0.00%) 
Vulvovaginal candidiasis  1  1/477 (0.21%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Injury, poisoning and procedural complications         
Adverse event following immunisation  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  0/464 (0.00%) 
Anal injury  1  0/477 (0.00%)  0/479 (0.00%)  0/445 (0.00%)  1/464 (0.22%) 
Burns second degree  1  1/477 (0.21%)  0/479 (0.00%)  1/445 (0.22%)  0/464 (0.00%) 
Femur fracture  1  0/477 (0.00%)  0/479 (0.00%)  0/445 (0.00%)  1/464 (0.22%) 
Foreign body in respiratory tract  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  0/464 (0.00%) 
Induced abortion failed  1  0/477 (0.00%)  1/479 (0.21%)  0/445 (0.00%)  0/464 (0.00%) 
Postoperative wound complication  1  1/477 (0.21%)  1/479 (0.21%)  0/445 (0.00%)  0/464 (0.00%) 
Uterine rupture  1  0/477 (0.00%)  1/479 (0.21%)  0/445 (0.00%)  0/464 (0.00%) 
Investigations         
Haemoglobin decreased  1  1/477 (0.21%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Metabolism and nutrition disorders         
Diabetes mellitus  1  0/477 (0.00%)  1/479 (0.21%)  0/445 (0.00%)  0/464 (0.00%) 
Malnutrition  1  0/477 (0.00%)  0/479 (0.00%)  2/445 (0.45%)  2/464 (0.43%) 
Musculoskeletal and connective tissue disorders         
Symphysiolysis  1  1/477 (0.21%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Non-Hodgkin's lymphoma  1  0/477 (0.00%)  1/479 (0.21%)  0/445 (0.00%)  0/464 (0.00%) 
Nervous system disorders         
Convulsion neonatal  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  0/464 (0.00%) 
Headache  1  2/477 (0.42%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Hypocalcaemic seizure  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  0/464 (0.00%) 
Hypoxic-ischaemic encephalopathy  1  0/477 (0.00%)  0/479 (0.00%)  2/445 (0.45%)  1/464 (0.22%) 
Intercostal neuralgia  1  1/477 (0.21%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Paraparesis  1  1/477 (0.21%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Pregnancy, puerperium and perinatal conditions         
Abortion spontaneous  1  2/477 (0.42%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Eclampsia  1  1/477 (0.21%)  1/479 (0.21%)  0/445 (0.00%)  0/464 (0.00%) 
False labour  1  0/477 (0.00%)  1/479 (0.21%)  0/445 (0.00%)  0/464 (0.00%) 
Foetal death  1  12/477 (2.52%)  9/479 (1.88%)  0/445 (0.00%)  0/464 (0.00%) 
Foetal distress syndrome  1  0/477 (0.00%)  2/479 (0.42%)  0/445 (0.00%)  0/464 (0.00%) 
Foetal growth restriction  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  1/464 (0.22%) 
Foetal hypokinesia  1  0/477 (0.00%)  1/479 (0.21%)  0/445 (0.00%)  0/464 (0.00%) 
Gestational hypertension  1  5/477 (1.05%)  5/479 (1.04%)  0/445 (0.00%)  0/464 (0.00%) 
Haemorrhage in pregnancy  1  2/477 (0.42%)  3/479 (0.63%)  0/445 (0.00%)  0/464 (0.00%) 
Hyperemesis gravidarum  1  0/477 (0.00%)  1/479 (0.21%)  0/445 (0.00%)  0/464 (0.00%) 
Jaundice neonatal  1  0/477 (0.00%)  0/479 (0.00%)  0/445 (0.00%)  1/464 (0.22%) 
Low birth weight baby  1  0/477 (0.00%)  0/479 (0.00%)  3/445 (0.67%)  3/464 (0.65%) 
Meconium stain  1  0/477 (0.00%)  0/479 (0.00%)  0/445 (0.00%)  1/464 (0.22%) 
Peripartum cardiomyopathy  1  1/477 (0.21%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Placenta praevia  1  0/477 (0.00%)  1/479 (0.21%)  0/445 (0.00%)  0/464 (0.00%) 
Postpartum haemorrhage  1  0/477 (0.00%)  1/479 (0.21%)  0/445 (0.00%)  0/464 (0.00%) 
Pre-eclampsia  1  8/477 (1.68%)  2/479 (0.42%)  0/445 (0.00%)  0/464 (0.00%) 
Premature baby  1  0/477 (0.00%)  0/479 (0.00%)  10/445 (2.25%)  12/464 (2.59%) 
Premature delivery  1  3/477 (0.63%)  2/479 (0.42%)  0/445 (0.00%)  0/464 (0.00%) 
Premature labour  1  2/477 (0.42%)  6/479 (1.25%)  0/445 (0.00%)  0/464 (0.00%) 
Premature rupture of membranes  1  0/477 (0.00%)  1/479 (0.21%)  0/445 (0.00%)  0/464 (0.00%) 
Premature separation of placenta  1  2/477 (0.42%)  1/479 (0.21%)  0/445 (0.00%)  0/464 (0.00%) 
Preterm premature rupture of membranes  1  1/477 (0.21%)  1/479 (0.21%)  0/445 (0.00%)  0/464 (0.00%) 
Prolonged rupture of membranes  1  2/477 (0.42%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Small for dates baby  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  0/464 (0.00%) 
Stillbirth  1  5/477 (1.05%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Threatened labour  1  1/477 (0.21%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Uterine inversion  1  1/477 (0.21%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Psychiatric disorders         
Confusional state  1  0/477 (0.00%)  1/479 (0.21%)  0/445 (0.00%)  0/464 (0.00%) 
Intentional self-injury  1  0/477 (0.00%)  1/479 (0.21%)  0/445 (0.00%)  0/464 (0.00%) 
Major depression  1  1/477 (0.21%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Renal and urinary disorders         
Urinary retention  1  1/477 (0.21%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Reproductive system and breast disorders         
Uterine atony  1  0/477 (0.00%)  1/479 (0.21%)  0/445 (0.00%)  0/464 (0.00%) 
Vaginal discharge  1  1/477 (0.21%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Acute respiratory distress syndrome  1  0/477 (0.00%)  0/479 (0.00%)  0/445 (0.00%)  1/464 (0.22%) 
Dyspnoea  1  0/477 (0.00%)  0/479 (0.00%)  0/445 (0.00%)  1/464 (0.22%) 
Meconium aspiration syndrome  1  0/477 (0.00%)  0/479 (0.00%)  6/445 (1.35%)  3/464 (0.65%) 
Neonatal asphyxia  1  0/477 (0.00%)  0/479 (0.00%)  5/445 (1.12%)  3/464 (0.65%) 
Neonatal respiratory distress  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  2/464 (0.43%) 
Neonatal respiratory distress syndrome  1  0/477 (0.00%)  0/479 (0.00%)  5/445 (1.12%)  5/464 (1.08%) 
Respiratory disorder  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  0/464 (0.00%) 
Transient tachypnoea of the newborn  1  0/477 (0.00%)  0/479 (0.00%)  1/445 (0.22%)  2/464 (0.43%) 
Skin and subcutaneous tissue disorders         
Drug eruption  1  0/477 (0.00%)  0/479 (0.00%)  0/445 (0.00%)  1/464 (0.22%) 
Surgical and medical procedures         
Abortion induced  1  1/477 (0.21%)  1/479 (0.21%)  0/445 (0.00%)  0/464 (0.00%) 
Vascular disorders         
Hypertension  1  1/477 (0.21%)  1/479 (0.21%)  0/445 (0.00%)  0/464 (0.00%) 
Hypotension  1  1/477 (0.21%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
Venous thrombosis  1  1/477 (0.21%)  0/479 (0.00%)  0/445 (0.00%)  0/464 (0.00%) 
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Mother/Immediate INH Mother/Deferred INH Infant/Immediate INH Infant/Deferred INH
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   438/477 (91.82%)   449/479 (93.74%)   417/445 (93.71%)   430/464 (92.67%) 
Congenital, familial and genetic disorders         
Congenital umbilical hernia  1  0/477 (0.00%)  0/479 (0.00%)  36/445 (8.09%)  41/464 (8.84%) 
Gastrointestinal disorders         
Abdominal pain  1  24/477 (5.03%)  15/479 (3.13%)  2/445 (0.45%)  0/464 (0.00%) 
Diarrhoea  1  37/477 (7.76%)  25/479 (5.22%)  79/445 (17.75%)  83/464 (17.89%) 
General disorders         
Pyrexia  1  12/477 (2.52%)  11/479 (2.30%)  51/445 (11.46%)  57/464 (12.28%) 
Infections and infestations         
Conjunctivitis  1  17/477 (3.56%)  14/479 (2.92%)  29/445 (6.52%)  26/464 (5.60%) 
Gastroenteritis  1  25/477 (5.24%)  20/479 (4.18%)  58/445 (13.03%)  50/464 (10.78%) 
Oral candidiasis  1  1/477 (0.21%)  1/479 (0.21%)  25/445 (5.62%)  24/464 (5.17%) 
Upper respiratory tract infection  1  15/477 (3.14%)  23/479 (4.80%)  45/445 (10.11%)  48/464 (10.34%) 
Urinary tract infection  1  55/477 (11.53%)  51/479 (10.65%)  2/445 (0.45%)  2/464 (0.43%) 
Vulvovaginal candidiasis  1  52/477 (10.90%)  47/479 (9.81%)  0/445 (0.00%)  0/464 (0.00%) 
Investigations         
Alanine aminotransferase increased  1  187/477 (39.20%)  206/479 (43.01%)  31/445 (6.97%)  31/464 (6.68%) 
Aspartate aminotransferase increased  1  141/477 (29.56%)  151/479 (31.52%)  9/445 (2.02%)  2/464 (0.43%) 
Blood alkaline phosphatase increased  1  12/477 (2.52%)  26/479 (5.43%)  2/445 (0.45%)  1/464 (0.22%) 
Blood glucose decreased  1  144/477 (30.19%)  128/479 (26.72%)  1/445 (0.22%)  1/464 (0.22%) 
Blood glucose increased  1  40/477 (8.39%)  47/479 (9.81%)  0/445 (0.00%)  0/464 (0.00%) 
Haemoglobin decreased  1  199/477 (41.72%)  191/479 (39.87%)  353/445 (79.33%)  365/464 (78.66%) 
Neutrophil count decreased  1  81/477 (16.98%)  87/479 (18.16%)  270/445 (60.67%)  264/464 (56.90%) 
Platelet count decreased  1  22/477 (4.61%)  10/479 (2.09%)  23/445 (5.17%)  26/464 (5.60%) 
Weight decreased  1  96/477 (20.13%)  97/479 (20.25%)  15/445 (3.37%)  12/464 (2.59%) 
Metabolism and nutrition disorders         
Failure to thrive  1  0/477 (0.00%)  0/479 (0.00%)  23/445 (5.17%)  23/464 (4.96%) 
Musculoskeletal and connective tissue disorders         
Growth failure  1  0/477 (0.00%)  0/479 (0.00%)  47/445 (10.56%)  38/464 (8.19%) 
Nervous system disorders         
Neuropathy peripheral  1  94/477 (19.71%)  109/479 (22.76%)  0/445 (0.00%)  0/464 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  46/477 (9.64%)  35/479 (7.31%)  66/445 (14.83%)  87/464 (18.75%) 
Vascular disorders         
Hypertension  1  40/477 (8.39%)  37/479 (7.72%)  0/445 (0.00%)  0/464 (0.00%) 
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Melissa Allen, Director, IMPAACT Operations Center
Organization: Family Health International (FHI 360)
Phone: (919) 405-1429
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01494038     History of Changes
Other Study ID Numbers: P1078
10732 ( Registry Identifier: DAIDS ES )
IMPAACT P1078
First Submitted: December 14, 2011
First Posted: December 16, 2011
Results First Submitted: September 6, 2018
Results First Posted: November 20, 2018
Last Update Posted: November 20, 2018