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| Sponsor: | University of Cape Town |
|---|---|
| Collaborators: |
University of Stellenbosch Medical Research Council Rockefeller Foundation |
| Information provided by: | University of Cape Town |
| ClinicalTrials.gov Identifier: | NCT00330304 |
Purpose
The study involves use of isoniazid and cotrimoxazole as strategies for preventing infections in HIV-infected children and reducing mortality. Cotrimoxazole is well known to reduce mortality and infections in HIV-infected children and is currently the recommended standard of care. However, isoniazid has only been studied in HIV-infected adults (in whom it has been shown to substantially reduce the incidence of tuberculosis). In a randomised controlled study of isoniazid in HIV-infected children, we found that INH reduced mortality and tuberculosis incidence in excess of 50%; the data safety monitoring board recommended termination of the placebo arm given the beneficial effects of INH. We therefore aim to follow-up these children to compare the long term impact of two different INH and CTX preventive regimens (daily versus thrice weekly) on morbidity, mortality, adherence and incidence of adverse reactions. We also aim to investigate the efficacy, safety and tolerability of INH compared with placebo for prevention of TB in children receiving HAART as the benefit in this group is unknown.
| Condition | Intervention | Phase |
|---|---|---|
|
Tuberculosis |
Drug: Isoniazid Drug: Cotrimoxazole |
Phase III |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Control: Placebo Control Endpoint Classification: Safety/Efficacy Study Intervention Model: Factorial Assignment Masking: Double-Blind Primary Purpose: Prevention |
| Official Title: | Long Term Study of 2 Isoniazid (INH) Prophylactic Regimens With Concomitant Cotrimoxazole (CTX) in HIV-Infected Children - Impact on Morbidity, Mortality, Bacterial Resistance and Incidence of Tuberculosis |
| Estimated Enrollment: | 450 |
| Study Start Date: | January 2003 |
| Estimated Study Completion Date: | May 2006 |
Tuberculosis (TB) and HIV are dual pandemics occurring in South Africa. Prevention of TB and the subsequent decline in immune function in HIV-infected children is an important strategy to reduce mortality. Isoniazid (INH) prophylaxis reduces TB incidence in HIV-infected adults, but the efficacy in HIV-infected children has not been studied. In 2003, we therefore began a double blind placebo controlled trial to investigate the impact of INH prophylaxis on mortality, morbidity and TB incidence in HIV-infected children. Interim analysis found a striking reduction in mortality and TB with a decrease in mortality in excess of 50% and 60% respectively, in children on INH. Based on this, the placebo arm was terminated; the study continued as a trial of thrice versus daily INH and cotrimoxazole (CTX). Although the results indicate an important benefit in children on INH, it is unknown what the long term efficacy and safety of INH prophylaxis is, what the optimal regime is and whether this pertains to children on HAART (who formed a minority of the cohort but who are still at risk for TB).
Aim To investigate the efficacy, safety and tolerability of INH and CTX as prophylactic strategies for HIV-infected children in a high TB prevalence area.
Objectives
Methods A prospective randomized double blind placebo controlled study of INH versus placebo in newly recruited HIV-infected children who are stable on HAART. In addition, an extended follow-up study of children already randomised to thrice weekly or daily INH and CTX. Children will be followed for 2 years with regular clinical evaluation, adherence assessment and laboratory monitoring. Outcomes measured will be mortality, TB incidence, morbidity, adherence and tolerability.
Eligibility| Ages Eligible for Study: | 8 Weeks to 15 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contacts and Locations| Contact: Heather J Zar, MD PhD | 27216585350 | hzar@ich.uct.ac.za |
| Contact: Mark Cotton, MD PhD | 27219384219 | mcot@sun.ac.za |
| South Africa, Western Cape | |
| Red Cross Childrens Hospital | Recruiting |
| Cape Town, Western Cape, South Africa, 7700 | |
| Contact: Heather zar, MD PhD 27216585350 hzar@ich.uct.ac.za | |
| Tygerberg Hospital | Recruiting |
| Cape Town, Western Cape, South Africa | |
| Contact: Mark Cotton, MD, PhD 27219384219 mcot@sun.ac.za | |
| Principal Investigator: | Heather J Zar, MD PHd | University of Cape Town |
| Principal Investigator: | Mark Cotton, Md PhD | Stellenbosch University |
More Information
| Study ID Numbers: | 299/2005 |
| Study First Received: | May 24, 2006 |
| Last Updated: | May 24, 2006 |
| ClinicalTrials.gov Identifier: | NCT00330304 History of Changes |
| Health Authority: | South Africa: Medicines Control Council |
|
Tuberculosis Child HIV prophylaxis mortality |
|
Bacterial Infections Antimetabolites Anti-Infective Agents Antiprotozoal Agents Molecular Mechanisms of Pharmacological Action Antilipemic Agents Anti-Infective Agents, Urinary Trimethoprim-Sulfamethoxazole Combination Renal Agents Actinomycetales Infections Pharmacologic Actions |
Antimalarials Anti-Bacterial Agents Antiparasitic Agents Gram-Positive Bacterial Infections Therapeutic Uses Mycobacterium Infections Tuberculosis Antitubercular Agents Fatty Acid Synthesis Inhibitors Isoniazid |
