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
Isoniazid (INH)
+ Trimethoprim/Sulfamethoxazole (TMP/SMX)
+ Isoniazid Placebo (PL)
Actinomycetales Infections+12
+ Bacterial Infections and Mycoses
+ Bacterial Infections
Prevention Study
Summary
Study start date: February 1, 2004
Actual date on which the first participant was enrolled.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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.1354 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Prevention Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Healthy volunteers allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
Inclusion Criteria: * Mother is HIV-infected. Hard copy documentation of the mother's HIV infection is unnecessary if a positive DNA PCR from her infant is available. * Received Bacille Calmette-Guerin (BCG) vaccine up to and including the 30th day of life and at least 90 days prior to study entry * Able to complete all study requirements * Physician assessment of age-appropriate neurodevelopment in which the chronological age is corrected for gestational age for prematurely born infants * Parent or legal guardian able and willing to provide signed informed consent * Plan to live in the study area for at least 4 years * For inclusion in HIV-infected stratum, infant must have a positive HIV-1 DNA PCR; for inclusion in HIV-uninfected stratum, infant must have a negative HIV-1 DNA PCR performed at \>= 4 weeks of age Exclusion Criteria: * Previous diagnosis of TB infection, TB disease or current treatment for TB infection or TB disease * Previous receipt of INH * Contact with a known acid fast bacilli (AFB) sputum smear or culture-positive case of TB before study entry * Current acute or recurrent (3 or more prior episodes) lower respiratory tract disease * Chronic persistent diarrhea * Failure to thrive * Contraindications for use of INH or TMP/SMX * Require certain medications * Known or suspected immune system diseases other than HIV * Current or previous diagnosis of or treatment for cancer * Current immunosuppressive therapy greater than 1 mg/kg/day of prednisone or equivalent * Anticipated long-term oral or intravenous corticosteroid therapy (greater than 3 weeks). Those receiving nonsteroidal anti-inflammatory agents and inhaled corticosteroids are not excluded. * Grade 3 or greater AST/SGOT, ALT/SGPT, ANC, hemoglobin, platelet count, rash, neuropathy, or myopathy at screening * Any Grade 4 clinical or laboratory toxicity within 14 days prior to study entry * Other acute or chronic conditions that, in the opinion of the investigator, may interfere with the study
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.4 intervention groups are designated in this study
50% chance of being blinded to the placebo group
Treatment Groups
Group I
ExperimentalGroup II
ExperimentalGroup III
PlaceboGroup IV
PlaceboStudy Objectives
Primary Objectives
Secondary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 6 locations
University of Cape Town, Red Cross Children's Hospital
Cape Town, South AfricaUniversity of Stellenbosch, Tygerberg Hospital
Cape Town, South AfricaNelson R. Mandela School of Medicine, University of KwaZulu Natal, Durban
Durban, South Africa