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REMEMBER: Reducing Early Mortality & Morbidity by Empiric Tuberculosis (TB) Treatment (REMEMBER)

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ClinicalTrials.gov Identifier: NCT01380080
Recruitment Status : Completed
First Posted : June 27, 2011
Results First Posted : February 23, 2016
Last Update Posted : March 7, 2017
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
AIDS Clinical Trials Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HIV Infection
Interventions Drug: Atripla (r)
Drug: Efavirenz
Drug: Truvada
Drug: Rifampin/isoniazid/pyrazinamide/ethambutol FDC
Drug: Rifampin/isoniazid FDC
Drug: Isoniazid
Enrollment 851
Recruitment Details Recruited at AIDS Clinical Trials Units in 10 international countries. Recruitment occurred between October 31, 2011 (date of first participant was randomized) and June 9, 2014 (date of last participant was randomized).
Pre-assignment Details 851 were randomized 1:1 to treatment strategies A and B. Results reported for 850 eligible participants; 1 was subsequently found ineligible and excluded from all analyses.
Arm/Group Title Arm A: Empiric Arm B: IPT
Hide Arm/Group Description Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
Period Title: Overall Study
Started 424 426
Completed 391 403
Not Completed 33 23
Reason Not Completed
Death             20             22
Withdrawal by Subject             4             0
Not able to get to clinic             4             0
Not willing to adhere to requirements             3             1
Lost to Follow-up             2             0
Arm/Group Title Arm A: Empiric Arm B: IPT Total
Hide Arm/Group Description Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH). Total of all reporting groups
Overall Number of Baseline Participants 424 426 850
Hide Baseline Analysis Population Description
Intent to treat: All eligible participants were included in the baseline characteristics.
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 424 participants 426 participants 850 participants
36
(30 to 42)
35
(30 to 42)
36
(30 to 42)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 424 participants 426 participants 850 participants
Female
200
  47.2%
200
  46.9%
400
  47.1%
Male
224
  52.8%
226
  53.1%
450
  52.9%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 424 participants 426 participants 850 participants
Black Non-Hispanic 375 384 759
Hispanic (Regardless of Race) 32 29 61
Asian, Pacific Islander 17 13 30
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 424 participants 426 participants 850 participants
Haiti 53 56 109
Malawi 95 98 193
Brazil 9 6 15
South Africa 86 90 176
Zimbabwe 25 27 52
Uganda 25 24 49
Zambia 17 19 36
Kenya 77 75 152
Peru 20 19 39
India 17 12 29
HIV-1 RNA  
Median (Inter-Quartile Range)
Unit of measure:  Log10 copies/mL
Number Analyzed 424 participants 426 participants 850 participants
5.4
(5.0 to 5.7)
5.3
(4.9 to 5.7)
5.3
(4.9 to 5.7)
CD4+ T-cell count  
Median (Inter-Quartile Range)
Unit of measure:  Cells/mm^3
Number Analyzed 424 participants 426 participants 850 participants
18
(9 to 31)
19
(9 to 33)
18
(9 to 32)
1.Primary Outcome
Title Cumulative Probability of Death or Unknown Vital Status by Week 24
Hide Description

The Kaplan-Meier estimate of the cumulative probability of death or unknown vital status by week 24.

Vital status at week 48 and again at weeks 60, 72, 84, and 96 was determined for participants who do not complete study follow-up, including those who are prematurely discontinued from the study before week 24 without coming in to the clinic. Vital status for participants who are not discontinued from the study whenever a scheduled visit of any type is missed was also obtained. The vital status was considered unknown at week 24 if a participant prematurely discontinued from the study before week 24 and no vital status was obtained at week 48.

Time Frame From study entry to week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment
Arm/Group Title Arm A: Empiric Arm B: IPT
Hide Arm/Group Description:
Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only
Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
Overall Number of Participants Analyzed 424 426
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Cumulative probablity per 100 persons
5.2
(3.5 to 7.8)
5.2
(3.4 to 7.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: Empiric, Arm B: IPT
Comments Treatment comparison was made using the difference (arm B- arm A) in the Kaplan-Meier estimate for 24 week cumulative probability of death or unknown vital status with 95% confidence interval
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.97
Comments [Not Specified]
Method z-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Cumulative probability difference
Estimated Value -0.06
Confidence Interval (2-Sided) 95%
-3.05 to 2.94
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Cumulative Probability of Death by Week 24
Hide Description The Kaplan-Meier estimate of cumulative probability of death by week 24
Time Frame From study entry to week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment
Arm/Group Title Arm A: Empiric Arm B: IPT
Hide Arm/Group Description:
Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only
Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
Overall Number of Participants Analyzed 424 426
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Cumulative probablity per 100 persons
4.8
(3.1 to 7.3)
5.2
(3.4 to 7.8)
3.Secondary Outcome
Title Cumulative Probability of First AIDS Progression by Week 96
Hide Description The Kaplan-Meier estimate of the cumulative probability of first AIDS progression which was defined as the identification of a new World Health Organization (WHO) stage 3 or 4 condition
Time Frame From study entry to week 96
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Cumulative Probability of Death or AIDS Progression by Week 24
Hide Description

The Kaplan-Meier estimate of the cumulative probability of death or AIDS progression by week 24

The result of cumulative probability of death or AIDS progression by week 48 will be submitted after the study is completed. AIDS progression was defined as new WHO stage 3 or 4 conditions occurred after study entry.

Time Frame From study entry to week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment
Arm/Group Title Arm A: Empiric Arm B: IPT
Hide Arm/Group Description:
Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only
Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
Overall Number of Participants Analyzed 424 426
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Cumulative probablity per 100 persons
17.1
(13.9 to 21.1)
12.5
(9.7 to 16.0)
5.Secondary Outcome
Title Proportion of Participants With HIV-1 RNA Level <400 Copies/mL
Hide Description Proportion of participants with HIV-1 RNA level <400 copies/mL at weeks 0, 4, and 24. The results at week 48 will be submitted after the study is completed
Time Frame At weeks 0, 4, 24, and 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment. Missing data were assumed missing completed at random
Arm/Group Title Arm A: Empiric Arm B: IPT
Hide Arm/Group Description:
Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only
Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
Overall Number of Participants Analyzed 424 426
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
Week 0 (nA=420, nB=424)
0
(0 to 0.02)
0.01
(0 to 0.03)
Week 4 (nA=377, nB=371)
0.46
(0.41 to 0.51)
0.49
(0.44 to 0.55)
Week 24 (nA=370, nB=378)
0.84
(0.79 to 0.87)
0.85
(0.81 to 0.89)
6.Secondary Outcome
Title CD4+ T-cell Count
Hide Description The absolute levels of CD4+ T-cell counts (cells/mm^3) at weeks 0, 4, and 24. The results at week 48 will be submitted after the study is completed
Time Frame At weeks 0, 4, 24, and 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat: All eligible participants were included in the analysis: Participants were analyzed per original assigned randomized treatment. Missing data were assigned missing completely at random.
Arm/Group Title Arm A: Empiric Arm B: IPT
Hide Arm/Group Description:
Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only
Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
Overall Number of Participants Analyzed 424 426
Median (Inter-Quartile Range)
Unit of Measure: cells/ mm^3
Week 0 (nA=422, nB=425)
18
(9 to 31)
19
(9 to 33)
Week 4 (nA=406, nB=406)
74
(37 to 118)
76
(41 to 123)
Week 24 (nA=387, nB=393)
121
(75 to 172)
121
(80 to 188)
7.Secondary Outcome
Title CD4+ T-cell Count Change From Baseline
Hide Description Change was calculated as the CD4+ T-cell count at week (4 and 24) minus the baseline CD4+ T-cell count. The results at week 48 will be submitted after the study is completed
Time Frame From study entry to weeks 4, 24 and 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment. Missing data were assumed missing completely at random.
Arm/Group Title Arm A: Empiric Arm B: IPT
Hide Arm/Group Description:
Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only
Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
Overall Number of Participants Analyzed 424 426
Median (Inter-Quartile Range)
Unit of Measure: cells/ mm^3
Week 4 (nA=404, nB=405)
49
(20 to 91)
54
(22 to 94)
Week 24 (nA=385, nB=392)
96
(55 to 147)
102
(60 to 159)
8.Secondary Outcome
Title Time to Initiation of TB Treatment by Week 96
Hide Description Median time to TB treatment initiation by week 96
Time Frame From study entry to week 96
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Proportion of Participants With TB Diagnosis Per Current ACTG Diagnosis Appendix by Week 96
Hide Description Proportion of participants with TB diagnosis per current ACTG Diagnosis Appendix 60 by week 96
Time Frame From study entry to week 96
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Proportion of Participants With at Least One New Grade 3 or 4 Adverse Event That is at Least a One-grade Increase From Baseline by Week 48
Hide Description Proportion of participants with at least one new Grade 3 or 4 laboratory or sign or symptom that is at least a one-grade increase from baseline by Week 48
Time Frame From study entry to week 48
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Proportion of Participants With at Least One New Grade 3 or 4 That is at Least a One-grade Increase From Baseline for the Following Targeted Laboratory Values by Week 48
Hide Description

Proportion of participants with at least one new Grade 3 or 4 that is at least a one-grade increase from baseline for the following targeted laboratory values by Week 48

The targeted laboratory events include hemoglobin, serum creatinine, ALT and AST

Time Frame From study entry to week 48
Outcome Measure Data Not Reported
12.Secondary Outcome
Title Proportion of Participants With IRIS (Using Current ACTG Definition) by Week 48
Hide Description Proportion of participants with IRIS (using current ACTG definition Appendix 60) by Week 48
Time Frame From study entry to week 48
Outcome Measure Data Not Reported
13.Secondary Outcome
Title Proportion of Participants With Reportable Hospitalization by Week 48
Hide Description Proportion of participants with any hospitalization reported by Week 48
Time Frame From study entry to week 48
Outcome Measure Data Not Reported
14.Secondary Outcome
Title Proportion of Participants Who Prematurely Discontinued Any Component of TB Treatment by Week 48
Hide Description Proportion of participants with premature discontinuation of any component of TB treatment by Week 48
Time Frame From study entry to week 48
Outcome Measure Data Not Reported
15.Secondary Outcome
Title Proportion of Participants Who Prematurely Discontinued Antiretroviral Therapy by Week 48
Hide Description Proportion of participants with premature discontinuation of antiretroviral therapy (ART) by Week 48
Time Frame From study entry to week 48
Outcome Measure Data Not Reported
Time Frame From treatment dispensation to up to week 24
Adverse Event Reporting Description The protocol required reporting of signs and symptoms and laboratory abnormalities of >=Grade 2 and all grades of fever. The DAIDS Adverse Event (AE) Grading Table, Version 1.0, December 2004 (Clarification, August 2009) was used for grading of AEs. Expedited adverse event reporting followed Version 2.0 of the DAIDS Expedited Adverse Event Manual.
 
Arm/Group Title Arm A: Empiric Arm B: IPT
Hide Arm/Group Description Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
All-Cause Mortality
Arm A: Empiric Arm B: IPT
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Arm A: Empiric Arm B: IPT
Affected / at Risk (%) Affected / at Risk (%)
Total   81/424 (19.10%)   91/426 (21.36%) 
Blood and lymphatic system disorders     
Anaemia  1  8/424 (1.89%)  7/426 (1.64%) 
Disseminated intravascular coagulation  1  0/424 (0.00%)  1/426 (0.23%) 
Leukopenia  1  1/424 (0.24%)  0/426 (0.00%) 
Lymphadenopathy  1  1/424 (0.24%)  0/426 (0.00%) 
Lymphopenia  1  0/424 (0.00%)  1/426 (0.23%) 
Neutropenia  1  1/424 (0.24%)  0/426 (0.00%) 
Thrombocytopenia  1  1/424 (0.24%)  0/426 (0.00%) 
Cardiac disorders     
Angina unstable  1  1/424 (0.24%)  0/426 (0.00%) 
Cardiac failure congestive  1  1/424 (0.24%)  0/426 (0.00%) 
Eye disorders     
Cataract  1  1/424 (0.24%)  0/426 (0.00%) 
Gastrointestinal disorders     
Diarrhoea  1  6/424 (1.42%)  1/426 (0.23%) 
Enteritis  1  1/424 (0.24%)  0/426 (0.00%) 
Faecaloma  1  0/424 (0.00%)  1/426 (0.23%) 
Food poisoning  1  0/424 (0.00%)  1/426 (0.23%) 
Gastritis  1  2/424 (0.47%)  0/426 (0.00%) 
Haemorrhoids  1  0/424 (0.00%)  1/426 (0.23%) 
Intestinal obstruction  1  0/424 (0.00%)  1/426 (0.23%) 
Vomiting  1  2/424 (0.47%)  0/426 (0.00%) 
General disorders     
Asthenia  1  0/424 (0.00%)  1/426 (0.23%) 
Death  1  2/424 (0.47%)  6/426 (1.41%) 
Multi-organ failure  1  0/424 (0.00%)  1/426 (0.23%) 
Hepatobiliary disorders     
Drug-induced liver injury  1  4/424 (0.94%)  3/426 (0.70%) 
Hepatitis  1  0/424 (0.00%)  1/426 (0.23%) 
Hepatitis acute  1  1/424 (0.24%)  0/426 (0.00%) 
Hepatitis alcoholic  1  0/424 (0.00%)  1/426 (0.23%) 
Hepatotoxicity  1  0/424 (0.00%)  1/426 (0.23%) 
Hyperbilirubinaemia  1  2/424 (0.47%)  0/426 (0.00%) 
Hypertransaminasaemia  1  0/424 (0.00%)  1/426 (0.23%) 
Immune system disorders     
Drug hypersensitivity  1  0/424 (0.00%)  1/426 (0.23%) 
Immune reconstitution inflammatory syndrome  1  0/424 (0.00%)  1/426 (0.23%) 
Infections and infestations     
AIDS dementia complex  1  0/424 (0.00%)  1/426 (0.23%) 
Acquired immunodeficiency syndrome  1  1/424 (0.24%)  0/426 (0.00%) 
Atypical pneumonia  1  1/424 (0.24%)  0/426 (0.00%) 
Bacterial sepsis  1  2/424 (0.47%)  2/426 (0.47%) 
Bronchitis  1  0/424 (0.00%)  1/426 (0.23%) 
Cellulitis  1  1/424 (0.24%)  1/426 (0.23%) 
Central nervous system infection  1  0/424 (0.00%)  1/426 (0.23%) 
Cerebral toxoplasmosis  1  1/424 (0.24%)  0/426 (0.00%) 
Cytomegalovirus chorioretinitis  1  1/424 (0.24%)  0/426 (0.00%) 
Diarrhoea infectious  1  0/424 (0.00%)  1/426 (0.23%) 
Disseminated tuberculosis  1  1/424 (0.24%)  1/426 (0.23%) 
Furuncle  1  0/424 (0.00%)  1/426 (0.23%) 
Gastroenteritis  1  5/424 (1.18%)  6/426 (1.41%) 
HIV infection  1  0/424 (0.00%)  1/426 (0.23%) 
Histoplasmosis disseminated  1  1/424 (0.24%)  0/426 (0.00%) 
Immune reconstitution inflammatory syndrome associated tuberculosis  1  1/424 (0.24%)  0/426 (0.00%) 
Lobar pneumonia  1  1/424 (0.24%)  0/426 (0.00%) 
Lymph node tuberculosis  1  2/424 (0.47%)  0/426 (0.00%) 
Malaria  1  3/424 (0.71%)  2/426 (0.47%) 
Meningitis  1  1/424 (0.24%)  1/426 (0.23%) 
Meningitis bacterial  1  0/424 (0.00%)  2/426 (0.47%) 
Meningitis cryptococcal  1  6/424 (1.42%)  9/426 (2.11%) 
Meningitis tuberculous  1  1/424 (0.24%)  5/426 (1.17%) 
Meningitis viral  1  1/424 (0.24%)  1/426 (0.23%) 
Neurosyphilis  1  1/424 (0.24%)  0/426 (0.00%) 
Oesophageal candidiasis  1  1/424 (0.24%)  0/426 (0.00%) 
Periorbital cellulitis  1  0/424 (0.00%)  1/426 (0.23%) 
Peritonitis  1  1/424 (0.24%)  0/426 (0.00%) 
Pneumocystis jirovecii pneumonia  1  1/424 (0.24%)  1/426 (0.23%) 
Pneumonia  1  5/424 (1.18%)  2/426 (0.47%) 
Pneumonia bacterial  1  5/424 (1.18%)  3/426 (0.70%) 
Pulmonary tuberculosis  1  1/424 (0.24%)  0/426 (0.00%) 
Pyelonephritis  1  0/424 (0.00%)  1/426 (0.23%) 
Respiratory tract infection  1  0/424 (0.00%)  1/426 (0.23%) 
Salmonella sepsis  1  1/424 (0.24%)  1/426 (0.23%) 
Sepsis  1  2/424 (0.47%)  3/426 (0.70%) 
Subcutaneous abscess  1  1/424 (0.24%)  0/426 (0.00%) 
Tuberculoma of central nervous system  1  0/424 (0.00%)  1/426 (0.23%) 
Tuberculosis  1  3/424 (0.71%)  1/426 (0.23%) 
Typhoid fever  1  0/424 (0.00%)  1/426 (0.23%) 
Upper respiratory tract infection  1  1/424 (0.24%)  0/426 (0.00%) 
Urinary tract infection  1  1/424 (0.24%)  0/426 (0.00%) 
Urosepsis  1  0/424 (0.00%)  1/426 (0.23%) 
Viral vasculitis  1  0/424 (0.00%)  1/426 (0.23%) 
Injury, poisoning and procedural complications     
Head injury  1  1/424 (0.24%)  1/426 (0.23%) 
Lower limb fracture  1  0/424 (0.00%)  1/426 (0.23%) 
Investigations     
Haemoglobin decreased  1  0/424 (0.00%)  1/426 (0.23%) 
Hepatic enzyme increased  1  1/424 (0.24%)  1/426 (0.23%) 
Neutrophil count decreased  1  3/424 (0.71%)  1/426 (0.23%) 
Weight decreased  1  2/424 (0.47%)  1/426 (0.23%) 
Metabolism and nutrition disorders     
Dehydration  1  5/424 (1.18%)  1/426 (0.23%) 
Gout  1  0/424 (0.00%)  1/426 (0.23%) 
Hyperkalaemia  1  0/424 (0.00%)  1/426 (0.23%) 
Hypokalaemia  1  1/424 (0.24%)  2/426 (0.47%) 
Hypophosphataemia  1  1/424 (0.24%)  0/426 (0.00%) 
Metabolic acidosis  1  0/424 (0.00%)  1/426 (0.23%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Anogenital warts  1  2/424 (0.47%)  0/426 (0.00%) 
Carcinoid tumour of the caecum  1  0/424 (0.00%)  1/426 (0.23%) 
Hairy cell leukaemia  1  0/424 (0.00%)  1/426 (0.23%) 
Kaposi's sarcoma  1  2/424 (0.47%)  1/426 (0.23%) 
Oesophageal carcinoma  1  0/424 (0.00%)  1/426 (0.23%) 
Nervous system disorders     
Cerebrovascular accident  1  0/424 (0.00%)  1/426 (0.23%) 
Dizziness  1  0/424 (0.00%)  1/426 (0.23%) 
Epilepsy  1  1/424 (0.24%)  0/426 (0.00%) 
Headache  1  0/424 (0.00%)  2/426 (0.47%) 
Ischaemic cerebral infarction  1  0/424 (0.00%)  1/426 (0.23%) 
Syncope  1  1/424 (0.24%)  0/426 (0.00%) 
Psychiatric disorders     
Acute psychosis  1  0/424 (0.00%)  2/426 (0.47%) 
Hallucination  1  1/424 (0.24%)  0/426 (0.00%) 
Reactive psychosis  1  0/424 (0.00%)  1/426 (0.23%) 
Suicide attempt  1  0/424 (0.00%)  1/426 (0.23%) 
Renal and urinary disorders     
Acute kidney injury  1  1/424 (0.24%)  3/426 (0.70%) 
Chronic kidney disease  1  1/424 (0.24%)  0/426 (0.00%) 
Renal failure  1  0/424 (0.00%)  1/426 (0.23%) 
Reproductive system and breast disorders     
Uterine prolapse  1  1/424 (0.24%)  0/426 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  1  1/424 (0.24%)  0/426 (0.00%) 
Pleural effusion  1  1/424 (0.24%)  0/426 (0.00%) 
Pneumonia aspiration  1  0/424 (0.00%)  1/426 (0.23%) 
Skin and subcutaneous tissue disorders     
Rash maculo-papular  1  1/424 (0.24%)  0/426 (0.00%) 
Stevens-Johnson syndrome  1  0/424 (0.00%)  1/426 (0.23%) 
Surgical and medical procedures     
Abortion induced  1  1/424 (0.24%)  0/426 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm A: Empiric Arm B: IPT
Affected / at Risk (%) Affected / at Risk (%)
Total   370/424 (87.26%)   375/426 (88.03%) 
Gastrointestinal disorders     
Abdominal pain  1  26/424 (6.13%)  26/426 (6.10%) 
Diarrhoea  1  38/424 (8.96%)  33/426 (7.75%) 
Leukoplakia oral  1  22/424 (5.19%)  18/426 (4.23%) 
Nausea  1  20/424 (4.72%)  22/426 (5.16%) 
Vomiting  1  36/424 (8.49%)  50/426 (11.74%) 
General disorders     
Pyrexia  1  41/424 (9.67%)  54/426 (12.68%) 
Infections and infestations     
Oral candidiasis  1  48/424 (11.32%)  49/426 (11.50%) 
Pulmonary tuberculosis  1  22/424 (5.19%)  12/426 (2.82%) 
Investigations     
Alanine aminotransferase increased  1  54/424 (12.74%)  70/426 (16.43%) 
Aspartate aminotransferase increased  1  99/424 (23.35%)  98/426 (23.00%) 
Blood albumin decreased  1  151/424 (35.61%)  159/426 (37.32%) 
Blood alkaline phosphatase increased  1  36/424 (8.49%)  42/426 (9.86%) 
Blood bicarbonate decreased  1  66/424 (15.57%)  72/426 (16.90%) 
Blood creatinine increased  1  25/424 (5.90%)  44/426 (10.33%) 
Blood potassium decreased  1  32/424 (7.55%)  31/426 (7.28%) 
Blood sodium decreased  1  143/424 (33.73%)  140/426 (32.86%) 
Haemoglobin decreased  1  118/424 (27.83%)  94/426 (22.07%) 
Neutrophil count decreased  1  160/424 (37.74%)  162/426 (38.03%) 
Platelet count decreased  1  31/424 (7.31%)  38/426 (8.92%) 
Weight decreased  1  32/424 (7.55%)  23/426 (5.40%) 
White blood cell count decreased  1  136/424 (32.08%)  130/426 (30.52%) 
Nervous system disorders     
Headache  1  24/424 (5.66%)  43/426 (10.09%) 
Reproductive system and breast disorders     
Vaginal discharge  1  22/424 (5.19%)  10/426 (2.35%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  40/424 (9.43%)  47/426 (11.03%) 
Oropharyngeal plaque  1  22/424 (5.19%)  13/426 (3.05%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.
Results Point of Contact
Name/Title: ACTG Clinicaltrials.gov Coordinator
Organization: ACTG Network Coordinating Center, Social & Scientific Systems, Inc.
Phone: (301) 628-3313
Publications:
M. Hosseinipour, G. Bisson, S., et al. Empiric TB therapy does not decrease early mortality compared to Isoniazid Preventive therapy in adults with advanced HIV initiating ART: Results of ACTG A5274 (REMEMBER study). Program and abstracts of the 8th IAS Conference on HIV Pathogenesis, Treatment and prevention; July 19-22, 2015; Vancouver, Canada. Abstract A-729-0105-03495
Johnstone Kumwenda, Amita Gupta, et al. Empiric TB therapy versus IPT in HIV-infected persons initiating ART (ACTG A5274 48 week results). Program and abstracts of the 2016 Conference on Retroviruses and Opportunistic Infections; February 22-25, 2016; Boston, Massachusetts. Abstract 16-1383
Gregory P. Bisson, Amita Gupta, et al. Urine LAM Testing in Advanced HIV-Infected Adults in a Trial of Empiric TB Therapy. Program and abstracts of the 2016 Conference on Retroviruses and Opportunistic Infections; February 22-25, 2016; Boston, Massachusetts. Abstract 16-1650
Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01380080     History of Changes
Other Study ID Numbers: ACTG A5274
1U01AI068636 ( U.S. NIH Grant/Contract )
First Submitted: June 22, 2011
First Posted: June 27, 2011
Results First Submitted: January 26, 2016
Results First Posted: February 23, 2016
Last Update Posted: March 7, 2017