NCT00080119

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

Terminated Phase 2/Phase 3 Results posted Last updated 17 January 2019

What this trial tests

Phase 2/Phase 3 trial testing Isoniazid (INH) in HIV Infection in 1,354 participants. Terminated before completion.

Timeline

1 February 2004

Primary endpoint
1 May 2009

1 May 2009

Quick facts

Lead sponsor	International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Phase	Phase 2/Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	prevention
Enrollment	1,354
Start date	1 February 2004
Primary completion	1 May 2009
Estimated completion	1 May 2009
Sites	6 locations across Botswana, South Africa

Drugs / interventions tested

• Isoniazid (INH) — full drug profile →
• Trimethoprim/Sulfamethoxazole (TMP/SMX)
• Isoniazid Placebo (PL) — full drug profile →

Conditions studied

• HIV Infection — all drugs for HIV Infection →
• Tuberculosis — all drugs for Tuberculosis →
• Pneumocystis Jiroveci Pneumonia — all drugs for Pneumocystis Jiroveci Pneumonia →

Sponsor

International Maternal Pediatric Adolescent AIDS Clinical Trials Group

Who can join

Adults 91 Days to 120 Days, any sex, with HIV Infection or Tuberculosis. Healthy volunteers can join.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Time to Development of Tuberculosis (TB) Disease or Death Among HIV-infected Children
  Time frame: Through to week 96
  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 minimu
• Time From Randomization to Development of TB Infection or Death Among Perinatally Exposed, HIV-uninfected Children
  Time frame: Through to week 96
  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 part

Sponsor's own description

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.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Primary isoniazid prophylaxis against tuberculosis in HIV-exposed children.
   Madhi SA, Nachman S, Violari A, Kim S, et al · · 2011 · cited 114× · PMID 21732834 · DOI 10.1056/nejmoa1011214
2. The association between the ratio of monocytes:lymphocytes at age 3 months and risk of tuberculosis (TB) in the first two years of life.
   Naranbhai V, Kim S, Fletcher H, Cotton MF, et al · · 2014 · cited 75× · PMID 25034889 · DOI 10.1186/s12916-014-0120-7
3. Low Vitamin-D Levels Combined with PKP3-SIGIRR-TMEM16J Host Variants Is Associated with Tuberculosis and Death in HIV-Infected and -Exposed Infants.
   Gupta A, Montepiedra G, Gupte A, Zeldow B, et al · · 2016 · cited 13× · PMID 26872154 · DOI 10.1371/journal.pone.0148649
4. Streptococcus pneumoniae colonization in pneumococcal vaccine-naïve human immunodeficiency virus-exposed infected and -uninfected South African children.
   Nunes MC, Kim S, Zeldow B, Violari A, et al · · 2020 · cited 1× · PMID 32118776 · DOI 10.1097/md.0000000000019353