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:
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
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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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.
No text entered.

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 [1]
[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.



  Outcome Measures
  Show All Outcome Measures

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

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

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

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

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

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 ]

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 ]

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

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 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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


  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:
unchecked 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.
unchecked 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.


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 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:
Publications automatically indexed to this study:

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