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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
Results First Received: July 1, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Participant, Care Provider, 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
  Hide Participant Flow

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 
Overall Participants Analyzed 
[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 
[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.
Centers for Disease Control (CDC) Disease Category [1] 
[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 
[1] Only for HIV-infected participants.
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 
[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.
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 
[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.
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 


  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:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Wende Levy, IMPAACT
ClinicalTrials.gov Identifier: NCT00080119     History of Changes
Other Study ID Numbers: PACTG P1041
U01AI068632 ( US NIH Grant/Contract Award Number )
Study First Received: March 23, 2004
Results First Received: July 1, 2010
Last Updated: February 10, 2011