NCT00080119

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

A Randomized, Double Blind, Placebo Controlled Trial to Determine the Efficacy of Isoniazid (INH) in Preventing Tuberculosis Disease and Latent Tuberculosis Infection Among Infants With Perinatal Exposure to HIV

• Status: Terminated
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 1,354 (actual)
• Sponsor: International Maternal Pediatric Adolescent AIDS Clinical Trials Group · Network
• Sex: All
• Age: 91 Days – 120 Days
• Healthy volunteers: Accepted

Summary

Tuberculosis (TB) is highly endemic in sub-Saharan Africa. The increased burden of TB in settings with high prevalence of the Human Immunodeficiency Virus (HIV) is associated with high rates of transmission of Mycobacterium tuberculosis (M.tb) to both adults and children. Children infected with TB have a higher risk of developing severe disease than adults with TB. The purpose of this study was to determine if the antibiotic isoniazid (INH) prevented TB infection in infants born to HIV-infected mothers.

Detailed description

Tuberculosis (TB) and the Human Immunodeficiency Virus (HIV) are major public health problems in southern Africa, and the incidence of TB in South Africa is among the highest in the world. TB is caused by the highly contagious bacterium Mycobacterium tuberculosis. The use of Isoniazid (INH) prophylaxis in adults has been associated with reduced risk of TB disease in high-risk populations. Delay in initiating INH prophylaxis in children has resulted in more cases of childhood TB infection. This study evaluated the effectiveness of INH prophylaxis in preventing TB infection in infants born to HIV-infected mothers in southern Africa. Infants were randomly assigned to receive either INH or placebo by mouth daily, beginning between the 91st and 120th day of life, and at least 90 days after Bacille Calmette-Guerin (BCG) vaccination. At sites in South Africa, HIV-infected infants received daily trimethoprim/sulfamethoxazole (TMP/SMX) as Pneumocystis jiroveci pneumonia (PCP) prophylaxis until at least 1 year of age; HIV-uninfected infants received TMP/SMX until at least 6 months of age. The study was to follow participants for 192 weeks. Study visits occurred at study entry and every 12 weeks until week 192. A physical exam and blood collection occurred at each study visit. Infants were assessed for peripheral neuropathy every 12 weeks until week 96 and for TB at weeks 96, 144, and 192. The study also assessed medication adherence. As of November 12, 2008, follow-up was revised. All participants were permanently discontinued from study follow-up by February 28, 2009 and no later than May 31, 2009. Only clinical evaluations were performed for all participants. For HIV-infected participants, the study drug was stopped at the next scheduled visit. For HIV-uninfected subjects, the study drug was discontinued immediately.

Conditions

• HIV Infection
• Tuberculosis
• Pneumocystis Jiroveci Pneumonia

Interventions

Type	Name	Description
DRUG	Isoniazid (INH)	Antibiotic for the prevention and treatment of TB
DRUG	Trimethoprim/Sulfamethoxazole (TMP/SMX)	Antibiotic for the prevention and treatment of pneumocystis pneumonia (PCP)
DRUG	Isoniazid Placebo (PL)	Isoniazid placebo and TMP/SMX

Timeline

• Start date: 2004-02-01
• Primary completion: 2009-05-01
• Completion: 2009-05-01
• First posted: 2004-03-25
• Last updated: 2019-02-05
• Results posted: 2010-10-19

Locations

6 sites across 2 countries: Botswana, South Africa