Prevention of Early Mortality by Presumptive Tuberculosis (TB) Treatment
Status:
Terminated
Trial end date:
2013-06-01
Target enrollment:
Participant gender:
Summary
This study investigates the prevention of early mortality in patients initiating
antiretroviral therapy (ART) in sub-Saharan Africa where 79% of the co-infected cases of TB
reside. Many published studies have shown a surprisingly high proportion of all patients
initiated on ART dying within 6 months (8-26%) with increasing risk with decreasing CD4 T
cell count. The majority (median 70%) occur in the first 3 months with the greatest
proportion of deaths due to previously undiagnosed tuberculosis (TB). The investigators will
enroll patients from 4 geographically diverse countries (Gabon, Mozambique, South Africa, and
Uganda) in a randomized open label clinical trial targeting a population of people with high
mortality risk; patients with CD4 T cell count < 50 cells/μl and body mass index (BMI) < 18
kg/m2. Severely immunocompromised patients with low BMI in the intervention arm will receive
presumptive anti-TB 4-drug chemotherapy and subsequently initiate ART within 2 weeks compared
to ART alone. The main objective is to measure and compare early mortality in the group
presumptively treated for TB in addition to ART. Other sub-objectives are to determine the
predictors of early mortality and the causes of death by autopsy (traditional and verbal), to
determine if presumptive anti-TB treatment affects viral suppression with ART, and to assess
incidence rates and characterize drug toxicity in patients dually treated. Because of the
high rates of TB co-infection in sub-Saharan Africa in the HIV-infected, the investigators
expect that patients presumptively treated for TB in addition to HIV will have a lower
mortality rate than patients receiving ART only. This trial is expected to be of great public
health benefit and generalisability.
Phase:
Phase 4
Details
Lead Sponsor:
Prof JMA Lange
Collaborator:
European and Developing Countries Clinical Trials Partnership (EDCTP)