Daily Isoniazid to Prevent Tuberculosis in Infants Born to Mothers With HIV

This study has been terminated.

(Data Safety Monitoring Board (DSMB) recommended stopping study due to futility)

Sponsor:

Collaborators:

National Institute of Allergy and Infectious Diseases (NIAID)

Comprehensive International Program of Research on AIDS

Secure the Future Foundation

Information provided by:

International Maternal Pediatric Adolescent AIDS Clinical Trials Group

ClinicalTrials.gov Identifier:

NCT00080119

First received: March 23, 2004

Last updated: February 10, 2011

Last verified: February 2011

History of Changes

Results First Received: July 1, 2010

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Caregiver, Investigator); Primary Purpose: Prevention
Conditions:	HIV Infection Tuberculosis Pneumocystis Jiroveci Pneumonia
Interventions:	Drug: Isoniazid (INH) Drug: Trimethoprim/Sulfamethoxazole (TMP/SMX) Drug: Isoniazid Placebo (PL)

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Study participants were recruited at four study sites, three in South Africa and one in Botswana, between December 13, 2004 and June 26, 2008

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Infants perinatally exposed to HIV 91-120 days with documented receipt of Bacille Calmette-Guerin (BCG) vaccine by 30 days (>=90 days since receipt), no previous diagnosis or treatment of TB or contact with known TB case, stratified by HIV and randomized to receive blinded INH or INH placebo. 3 participants randomized but did not start treatment.

Reporting Groups

	Description
HIVneg/INH	Perinatally exposed, HIV-uninfected (HIVneg) children receiving Isoniazid (INH)10-20 mg/kg orally once a day for 96 weeks + Trimethoprim/Sulfamethoxazole (TMP/SMX) 5 mg/kg of TMP component orally once a day until HIV status is confirmed and child is no longer at risk of acquiring HIV through breastfeeding
HIVneg/PL	Perinatally-exposed, HIV-uninfected (HIVneg) children receiving Isoniazid placebo (PL) orally once a day for 96 weeks + TMP/SMX 5 mg/kg of TMP component orally once a day until HIV status is confirmed and child is no longer at risk of acquiring HIV through breastfeeding
HIVpos/INH	HIV-infected (HIVpos) children receiving Isoniazid (INH) 10-20 mg/kg orally once a day for 96 weeks + TMP/SMX 5 mg/kg of TMP component orally once a day until one year of age. TMP/SMX may have been continued after one year of age according to WHO guidelines.
HIVpos/PL	HIV-infected (HIVpos) children receiving Isoniazid placebo (PL) orally once a day for 96 weeks + TMP/SMX 5 mg/kg of TMP component orally once a day until one year of age. TMP/SMX may have been continued after one year of age according to WHO guidelines.

Participant Flow: Overall Study

	HIVneg/INH	HIVneg/PL	HIVpos/INH	HIVpos/PL
STARTED	403	401	273	274
COMPLETED	347	339	108	111
NOT COMPLETED	56	62	165	163
Discontinued because of study closure	0	0	130	141
Unable to get to clinic	24	24	7	1
Consent withdrawn	13	17	4	6
Unwilling to adhere to study requirement	3	2	5	1
Lost to Follow-up	16	19	19	14

Baseline Characteristics

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Reporting Groups

	Description
HIVneg/INH	Perinatally exposed, HIV-uninfected (HIVneg) children receiving Isoniazid (INH)10-20 mg/kg orally once a day for 96 weeks + Trimethoprim/Sulfamethoxazole (TMP/SMX) 5 mg/kg of TMP component orally once a day until HIV status is confirmed and child is no longer at risk of acquiring HIV through breastfeeding
HIVneg/PL	Perinatally-exposed, HIV-uninfected (HIVneg) children receiving Isoniazid placebo (PL) orally once a day for 96 weeks + TMP/SMX 5 mg/kg of TMP component orally once a day until HIV status is confirmed and child is no longer at risk of acquiring HIV through breastfeeding
HIVpos/INH	HIV-infected (HIVpos) children receiving Isoniazid (INH) 10-20 mg/kg orally once a day for 96 weeks + TMP/SMX 5 mg/kg of TMP component orally once a day until one year of age. TMP/SMX may have been continued after one year of age according to WHO guidelines.
HIVpos/PL	HIV-infected (HIVpos) children receiving Isoniazid placebo (PL) orally once a day for 96 weeks + TMP/SMX 5 mg/kg of TMP component orally once a day until one year of age. TMP/SMX may have been continued after one year of age according to WHO guidelines.
Total	Total of all reporting groups

Baseline Measures

	HIVneg/INH	HIVneg/PL	HIVpos/INH	HIVpos/PL	Total
Number of Participants [units: participants]	403	401	273	274	1351
Age, Customized [units: participants]
91-100 days	258	253	171	192	874
101-110 days	71	84	56	33	244
111-120 days	74	64	46	49	233
Gender [units: participants]
Female	203	190	159	151	703
Male	200	211	114	123	648
Race/Ethnicity, Customized [units: participants]
Indigenous African	389	386	264	272	1311
Mixed ancestry/other	14	15	9	2	40
Age at receipt of Bacille Calmette-Guerin (BCG) vaccination (days) [units: participants]
<= 7 days	395	392	255	258	1300
8-29 days	8	9	18	16	51
Any smoker in household [units: participants]
Yes	191	177	120	131	619
No	211	224	153	141	729
Missing	1	0	0	2	3
Birth weight (grams) [units: participants]
<2500 grams	49	49	68	56	222
>= 2500 grams	354	352	205	218	1129
CD4% ^[1] [units: participants]
<20%	0	0	56	55	111
20%-<25%	0	0	40	46	86
>= 25%	0	0	162	157	319
Missing	0	0	14	13	27
Not applicable	403	401	1	3	808
Centers for Disease Control (CDC) Disease Category ^[2] [units: participants]
Category N or A	0	0	252	244	496
Category B	0	0	16	21	37
Category C	0	0	2	3	5
HIV-uninfected on repeat test	0	0	1	3	4
Missing	0	0	2	3	5
Not applicable (HIV-uninfected)	403	401	0	0	804
Caregiver currently smokes [units: participants]
Yes	11	25	16	10	62
No	392	376	257	264	1289
Ever breastfed [units: participants]
Yes	24	24	37	36	121
No	379	377	236	238	1230
HIV-1 RNA (copies/ml) ^[1] [units: participants]
<= 400 copies/ml	0	0	8	12	20
401 - <20,000 copies/ml	0	0	36	51	87
20,000 - < 750,000 copies/ml	0	0	91	86	177
>= 750,000 copies/ml	0	0	129	116	245
Missing	0	0	8	6	14
Not applicable	403	401	1	3	808
History of tuberculosis (TB) in mother [units: participants]
Yes	33	25	14	25	97
No	370	376	259	249	1254
Housing [units: participants]
Formal (brick) house	235	233	162	183	813
Informal (shack/wooden)	168	168	109	89	534
Hostel	0	0	2	0	2
Missing	0	0	0	2	2
On antiretrovirals at entry ^[3] [units: participants]
Yes	0	0	78	93	171
No	0	0	194	178	372
Not applicable	403	401	1	3	808
Site of enrollment [units: participants]
Johannesburg, S Africa	259	260	180	179	878
Cape Town, S Africa	140	138	66	65	409
Durban, S Africa	4	3	26	27	60
Gaborone, Botswana	0	0	1	3	4

[1]	Only for HIV-infected participants. Those in the HIV-infected stratum that were later determined to be HIV-uninfected are recorded as not applicable.
[2]	Only for HIV-infected participants.
[3]	Only for HIV-infected participants. Those in the HIV-infected stratum that were later determined to be HIV-uninfected are recorded as not applicable.

Outcome Measures

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1. Primary:

Time to Development of Tuberculosis (TB) Disease or Death Among HIV-infected Children [ Time Frame: Through to week 96 ]

Measure Type	Primary
Measure Title	Time to Development of Tuberculosis (TB) Disease or Death Among HIV-infected Children
Measure Description	Criteria for diagnosis with TB disease: Definite-isolation of Mycobacterium TB (M.tb) or +ve stain on cerebrospinal fluid (CSF); Probable- +ve acid fast bacilli (AFB) stain on fluids/tissues other than CSF and sufficient clinical criteria/radiographic evidence suggestive of TB; Possible-abnormal chest radiograph suggestive of pulmonary TB (PTB) and either a +ve tuberculin skin test (TST) or minimum score on algorithm for clinical TB. Records reviewed by Endpoint Review Group. Results report percent of participants reaching TB disease/death by week 96 calculated using the Kaplan-Meier method.
Time Frame	Through to week 96
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Includes HIVpos who started study treatment. Time from randomization to TB disease/death was calculated. Participants lost-to-follow-up (LTF) <96 wks (+12wks) censored at the time of LTF. Participants in follow-up at 96 wks free of TB disease censored at 96 wks. Participants on study when study discontinued censored at discontinuation visit.

Reporting Groups

	Description
HIVpos/INH	No text entered.
HIVpos/PL	No text entered.

Measured Values

	HIVpos/INH	HIVpos/PL
Number of Participants Analyzed [units: participants]	273	274
Time to Development of Tuberculosis (TB) Disease or Death Among HIV-infected Children [units: Percent of participants]	27.4	28.9

Statistical Analysis 1 for Time to Development of Tuberculosis (TB) Disease or Death Among HIV-infected Children

Groups ^[1]	All groups
Method ^[2]	Log Rank
P Value ^[3]	0.93
Hazard Ratio (HR) ^[4]	0.98
95% Confidence Interval	( 0.67 to 1.44 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Threshold p-value for significance = 0.0492
[4]	Other relevant estimation information:
	Hazard ratio for INH relative to Placebo

2. Primary:

Time From Randomization to Development of TB Infection or Death Among Perinatally Exposed, HIV-uninfected Children [ Time Frame: Through to week 96 ]

Measure Type	Primary
Measure Title	Time From Randomization to Development of TB Infection or Death Among Perinatally Exposed, HIV-uninfected Children
Measure Description	Criteria for diagnosis with TB infection were outlined in the protocol. TB infection included TB disease (see primary outcome measure 1 for definition) and latent TB infection. Latent TB infection was diagnosed by a positive tuberculin skin test (TST) based on a purified protein derivative (PPD) performed at week 96. Participant records were reviewed by an Endpoint Review Group to verify that participants had met the criteria for TB infection. Results report percent of participants reaching TB infection or death by week 96 calculated using the Kaplan-Meier method.
Time Frame	Through to week 96
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
HIVneg who started study treatment were included. Time from randomization to first of TB infection/death was calculated. Participants lost-to-follow-up before 96 wks were censored at the time of loss-to-follow-up. Participants in follow-up at 96 weeks (+12 week window) who were free of TB infection were censored at 96 weeks (+12 week window).

Reporting Groups

	Description
HIVneg/INH	No text entered.
HIVneg/PL	No text entered.

Measured Values

	HIVneg/INH	HIVneg/PL
Number of Participants Analyzed [units: participants]	403	401
Time From Randomization to Development of TB Infection or Death Among Perinatally Exposed, HIV-uninfected Children [units: Percent of participants]	10.9	12.6

Statistical Analysis 1 for Time From Randomization to Development of TB Infection or Death Among Perinatally Exposed, HIV-uninfected Children

Groups ^[1]	All groups
Method ^[2]	Log Rank
P Value ^[3]	0.43
Hazard Ratio (HR) ^[4]	0.85
95% Confidence Interval	( 0.55 to 1.30 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Threshold p-value for significance = 0.0493
[4]	Other relevant estimation information:
	Hazard ratio for INH relative to Placebo

3. Secondary:

Time From Randomization to Development of TB Infection or Death Among HIV-infected Children [ Time Frame: Through to week 96 ]

Measure Type	Secondary
Measure Title	Time From Randomization to Development of TB Infection or Death Among HIV-infected Children
Measure Description	Criteria for diagnosis with TB infection were outlined in the protocol. TB infection included TB disease (see primary outcome measure 1 for definition) and latent TB infection. Latent TB infection was diagnosed by a positive TST based on a PPD performed at week 96. Participant records were reviewed by an Endpoint Review Group to verify that participants had met the criteria for TB infection. Results report percent of participants reaching TB infection or death by week 96 calculated using the Kaplan-Meier method.
Time Frame	Through to week 96
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
HIVpos starting study treatment were included. Time from randomization to first of TB infection/death was calculated. Participants LTF <96 weeks (+12 wk) censored at the time LTF. Participants in follow-up at 96 wks free of TB infection censored at 96 wks. Participants on study when study discontinued were censored at discontinuation visit.

Reporting Groups

	Description
HIVpos/INH	No text entered.
HIVpos/PL	No text entered.

Measured Values

	HIVpos/INH	HIVpos/PL
Number of Participants Analyzed [units: participants]	273	274
Time From Randomization to Development of TB Infection or Death Among HIV-infected Children [units: Percent of participants]	29.4	32.8

No statistical analysis provided for Time From Randomization to Development of TB Infection or Death Among HIV-infected Children

4. Secondary:

Time From Randomization to HIV Disease Progression or Death Among HIV-infected Children [ Time Frame: Through to week 96 ]

Measure Type	Secondary
Measure Title	Time From Randomization to HIV Disease Progression or Death Among HIV-infected Children
Measure Description	HIV disease progression was defined as any advancement in Centers for Disease Control (CDC) disease category from entry or death. If a participant was CDC disease category C at entry progression was defined as death. Results report percent of participants with HIV progression or death by week 96 calculated using the Kaplan-Meier method.
Time Frame	Through to week 96
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Includes HIVpos starting study treatment. Time from randomization to first of disease progression/death calculated. Censored if LTF <96 wks, at 96 wks (if on study) or at discontinuation visit. Participants found to be HIVneg upon repeat testing could only progress by meeting a death endpoint.

Reporting Groups

	Description
HIVpos/INH	No text entered.
HIVpos/PL	No text entered.

Measured Values

	HIVpos/INH	HIVpos/PL
Number of Participants Analyzed [units: participants]	273	274
Time From Randomization to HIV Disease Progression or Death Among HIV-infected Children [units: Percent of participants]	30.6	22.5

No statistical analysis provided for Time From Randomization to HIV Disease Progression or Death Among HIV-infected Children

5. Secondary:

Time From Randomization to Development of TB Disease or Death Among Perinatally Exposed, HIV-uninfected Children [ Time Frame: Through to week 96 ]

Measure Type	Secondary
Measure Title	Time From Randomization to Development of TB Disease or Death Among Perinatally Exposed, HIV-uninfected Children
Measure Description	Criteria for diagnosis with TB disease were: Definite-isolation of M.tb or positive stain on CSF; Probable-positive AFB stain on fluids/tissues other than CSF and sufficient clinical criteria/radiographic evidence suggestive of TB; Possible-abnormal chest radiograph suggestive of PTB and either a +ve TST or minimum score on algorithm to diagnose clinical TB. All records were reviewed by an Endpoint Review Group to verify that participants had met the criteria for TB disease. Results report percent of participants reaching TB disease/death by week 96 calculated using the Kaplan-Meier method.
Time Frame	Through to week 96
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Includes HIVneg who started study treatment. Time from randomization to the first of TB disease/death was calculated. Participants lost-to-follow-up before 96 weeks (+12 week window)were censored at the time of loss-to-follow-up. Participants in follow-up at 96 weeks who were free of TB disease were censored at 96 weeks (+12 week window).

Reporting Groups

	Description
HIVneg/INH	No text entered.
HIVneg/PL	No text entered.

Measured Values

	HIVneg/INH	HIVneg/PL
Number of Participants Analyzed [units: participants]	403	401
Time From Randomization to Development of TB Disease or Death Among Perinatally Exposed, HIV-uninfected Children [units: Percent of participants]	8.3	9.1

No statistical analysis provided for Time From Randomization to Development of TB Disease or Death Among Perinatally Exposed, HIV-uninfected Children

6. Secondary:

Time From Randomization to Development of TB Disease Among HIV Infected and Perinatally Exposed, HIV-uninfected Children [ Time Frame: Through to week 96 ]

Measure Type	Secondary
Measure Title	Time From Randomization to Development of TB Disease Among HIV Infected and Perinatally Exposed, HIV-uninfected Children
Measure Description	Criteria for diagnosis with TB disease were: Definite-isolation of M.tb or positive stain on CSF; Probable-positive AFB stain on fluids/tissues other than CSF and sufficient clinical criteria/radiographic evidence suggestive of TB; Possible-abnormal chest radiograph suggestive of PTB and either a +ve TST or minimum score on algorithm to diagnose clinical TB. All records were reviewed by an Endpoint Review Group to verify that participants had met the criteria for TB disease. Results report percent of participants reaching TB disease/death by week 96 calculated using the Kaplan-Meier method.
Time Frame	Through to week 96
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Includes all starting study treatment. Time from randomization to development of TB disease was calculated. Participants LTF <96 wks (+12 wks) censored at time of LTF. Participants in follow-up at 96 wks free of TB disease censored at 96 wks. HIVpos on study when study discontinued were censored at their discontinuation visit.

Reporting Groups

	Description
HIVneg/INH	No text entered.
HIVneg/PL	No text entered.
HIVpos/INH	No text entered.
HIVpos/PL	No text entered.

Measured Values

	HIVneg/INH	HIVneg/PL	HIVpos/INH	HIVpos/PL
Number of Participants Analyzed [units: participants]	403	401	273	274
Time From Randomization to Development of TB Disease Among HIV Infected and Perinatally Exposed, HIV-uninfected Children [units: Percent of participants]	7.8	8.5	20.3	23.7

No statistical analysis provided for Time From Randomization to Development of TB Disease Among HIV Infected and Perinatally Exposed, HIV-uninfected Children

7. Secondary:

Time From Randomization to Development of TB Infection Among HIV-infected and Perinatally Exposed, HIV-uninfected Children [ Time Frame: Through to week 96 ]

Measure Type	Secondary
Measure Title	Time From Randomization to Development of TB Infection Among HIV-infected and Perinatally Exposed, HIV-uninfected Children
Measure Description	Criteria for diagnosis with TB infection were outlined in the protocol. TB infection included TB disease (see primary outcome measure 1 for definition) and latent TB infection. Latent TB infection was diagnosed by a positive TST based on a PPD performed at week 96. Participant records were reviewed by an Endpoint Review Group to verify that participants had met the criteria for TB infection. Results report percent of participants reaching TB infection by week 96 calculated using the Kaplan-Meier method.
Time Frame	Through to week 96
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Includes all starting study treatment. Time from randomization to development of TB infection was calculated. Participants LTF <96 weeks (+12 wks) censored at the time of LTF. Participants in follow-up at 96 wks free of TB infection were censored at 96 wks. HIVpos on study when study discontinued censored at their discontinuation visit.

Reporting Groups

	Description
HIVneg/INH	No text entered.
HIVneg/PL	No text entered.
HIVpos/INH	No text entered.
HIVpos/PL	No text entered.

Measured Values

	HIVneg/INH	HIVneg/PL	HIVpos/INH	HIVpos/PL
Number of Participants Analyzed [units: participants]	403	401	273	274
Time From Randomization to Development of TB Infection Among HIV-infected and Perinatally Exposed, HIV-uninfected Children [units: Percent of participants]	10.4	12.1	22.4	27.9

No statistical analysis provided for Time From Randomization to Development of TB Infection Among HIV-infected and Perinatally Exposed, HIV-uninfected Children

8. Secondary:

Time From Randomization to Death Among HIV-infected and Perinatally Exposed, HIV-uninfected Children [ Time Frame: Through to week 96 ]

Measure Type	Secondary
Measure Title	Time From Randomization to Death Among HIV-infected and Perinatally Exposed, HIV-uninfected Children
Measure Description	Deaths from any cause were included. Results report percent of participants dying by week 96 calculated using the Kaplan-Meier method.
Time Frame	Through to week 96
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Includes all starting study treatment. Time from randomization to death was calculated. Participants LTF <96 weeks (+12 wks) censored at the time of LTF. Participants in follow-up at 96 wks (+12 wks) censored at 96 weeks. HIVpos on study when study was discontinued were censored at their discontinuation visit.

Reporting Groups

	Description
HIVneg/INH	No text entered.
HIVneg/PL	No text entered.
HIVpos/INH	No text entered.
HIVpos/PL	No text entered.

Measured Values

	HIVneg/INH	HIVneg/PL	HIVpos/INH	HIVpos/PL
Number of Participants Analyzed [units: participants]	403	401	273	274
Time From Randomization to Death Among HIV-infected and Perinatally Exposed, HIV-uninfected Children [units: Percent of participants]	0.8	0.8	11.6	7.2

No statistical analysis provided for Time From Randomization to Death Among HIV-infected and Perinatally Exposed, HIV-uninfected Children

9. Secondary:

Time From Randomization to First New Grade 3 or Worse Adverse Event Among HIV-infected and Perinatally Exposed, HIV-uninfected Children [ Time Frame: Through to week 96 ]

Measure Type	Secondary
Measure Title	Time From Randomization to First New Grade 3 or Worse Adverse Event Among HIV-infected and Perinatally Exposed, HIV-uninfected Children
Measure Description	Signs, symptoms and laboratory values were graded according to the Division of AIDS Adverse Event Grading System. Any event of grade 3 or higher not present at entry that occurred after randomization was classified as a new event. Results report percent of participants with a new event by week 96 calculated using the Kaplan-Meier method.
Time Frame	Through to week 96
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Includes all starting treatment. Time from randomization to first new adverse event (AE) calculated. For lab toxicities, censored at visit following permanent discontinuation of study drugs. For signs/symptoms, participants in follow-up at 96 wks (+12) with no new grade >=3 AE censored at 96 wks. Participants LTF <96 wks censored at LTF.

Reporting Groups

	Description
HIVneg/INH	No text entered.
HIVneg/PL	No text entered.
HIVpos/INH	No text entered.
HIVpos/PL	No text entered.

Measured Values

	HIVneg/INH	HIVneg/PL	HIVpos/INH	HIVpos/PL
Number of Participants Analyzed [units: participants]	403	401	273	274
Time From Randomization to First New Grade 3 or Worse Adverse Event Among HIV-infected and Perinatally Exposed, HIV-uninfected Children [units: Percent of participants]
New >=grade 3 sign/symptom	5.0	4.2	16.8	11.7
New >= grade 3 peripheral neuropathy	1.1	0.3	2.4	0.8
New >=grade 3 lab abnormality	4.9	4.6	11.3	10.1
New >=grade 3 hemoglobin	0.0	0.0	1.8	1.2
New >=grade 3 ANC	1.7	0.3	1.6	3.5
New >=grade 3 platelets	0.3	0.0	1.7	0.9
New >=grade 3 SGOT	1.0	2.8	0.4	2.5
New >=grade 3 SGPT	2.8	4.4	5.9	4.0

No statistical analysis provided for Time From Randomization to First New Grade 3 or Worse Adverse Event Among HIV-infected and Perinatally Exposed, HIV-uninfected Children

Serious Adverse Events

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Other Adverse Events

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More Information

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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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: In accordance with the Clinical Trial 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
DSMB recommended stopping study due to futility: "no compelling reason to enroll additional infants" or "to continue to treat participants with the blinded study medication". Week 192 analyses not done as <4% (26%) of HIVpos (HIVneg) reached wk 192

Results Point of Contact:

Name/Title: Clinicaltrials.gov Coordinator
Organization: Center for Biostatistics in AIDS Research, Harvard School of Public Health
phone: (617) 432-2829
e-mail: CBAR.ClinicalTrials.Gov@sdac.harvard.edu

Publications of Results:

Cotton MF, Schaaf HS, Lottering G, Weber HL, Coetzee J, Nachman S; PACTG 1041 Team. Tuberculosis exposure in HIV-exposed infants in a high-prevalence setting. Int J Tuberc Lung Dis. 2008 Feb;12(2):225-7.

Cotton M, Kim S, Rabie H, Coetzee J, Nachman S for the PACTG 1041 Team. A window into a public program for prevention of mother to child transmission of HIV: evidence from a prospective clinical trial. The Southern African Journal of HIV Medicine 10(4): 16-19, 2009.

Other Publications:

Chintu C, Mwaba P. Tuberculosis in children with human immunodeficiency virus infection. Int J Tuberc Lung Dis. 2005 May;9(5):477-84. Review.

Corbett EL, Watt CJ, Walker N, Maher D, Williams BG, Raviglione MC, Dye C. The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Arch Intern Med. 2003 May 12;163(9):1009-21. Review.

de Jong BC, Israelski DM, Corbett EL, Small PM. Clinical management of tuberculosis in the context of HIV infection. Annu Rev Med. 2004;55:283-301.

Toossi Z. Virological and immunological impact of tuberculosis on human immunodeficiency virus type 1 disease. J Infect Dis. 2003 Oct 15;188(8):1146-55. Epub 2003 Sep 30. Review.

Publications automatically indexed to this study:

Madhi SA, Nachman S, Violari A, Kim S, Cotton MF, Bobat R, Jean-Philippe P, McSherry G, Mitchell C; P1041 Study Team. Primary isoniazid prophylaxis against tuberculosis in HIV-exposed children. N Engl J Med. 2011 Jul 7;365(1):21-31.

Responsible Party:	Wende Levy, IMPAACT
ClinicalTrials.gov Identifier:	NCT00080119 History of Changes
Other Study ID Numbers:	PACTG P1041, U01AI068632
Study First Received:	March 23, 2004
Results First Received:	July 1, 2010
Last Updated:	February 10, 2011
Health Authority:	United States: Federal Government

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