Prevention of Early Mortality by Presumptive Tuberculosis (TB) Treatment

Phase 4

Terminated

• Conditions: HIV Infection; Tuberculosis
• Interventions: Drug: ART only arm

• Registration Number: NCT01417988
• Lead Sponsor: Prof JMA Lange

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-07-25
• Study Start: 2011-08
• Study First Submitted QC: 2011-08-15
• Study First Posted: 2011-08-16
• Primary Completion: 2013-06
• Study Completion: 2013-06
• Status Verified: 2014-02
• Last Update Submitted: 2014-02-14
• Last Update Posted: 2014-02-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

• Aged > 18 years old
• HIV-1 positive
• Eligible for antiretroviral treatment with CD4 T cell count < 50 cells/μl
• BMI < 18

Exclusion Criteria

• Patients with smear-positive pulmonary TB
• Patients who fulfill the diagnostic criteria for smear-negative pulmonary or extrapulmonary TB (http://www.who.int/tb/publications/2006/tbhiv_recommendations.pdf ).
• Previous TB treatment (history of TB medication for > 1 month
• History of using antiretroviral drugs
• Symptomatic known underlying liver disease or transaminases > 5x upper limit of normal
• Known or suspected drug resistance to more than one first-line TB drug according to WHO criteria but excluding HIV infection (e.g. household contacts of MDRTB patients)
• Pregnant or breast-feeding
• Patients with cryptococcal meningitis (CrAG positive with neurologic symptoms)
• Patients with other severe (opportunistic) disease such as disseminated KS, malignant lymphoma, toxoplasmosis who may not be able to tolerate anti-TB medication or require other specific therapy
• Patients with danger signs (respiratory rate > 30 per minute, heart rate > 120bpm, temperature > 39oC, and unable to ambulate)
• Taking other potentially life-saving medications (e.g. for other OIs, or immunosuppressants) that are incompatible with anti-TB chemotherapy or ART
• Unable to swallow TB medications
• Unable to follow-up at the clinic for regularly scheduled follow-up (e.g. too far from clinic)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ART only arm	ART only arm	ART (efavirenz-based) only (+ pyridoxine 50mg) given within 2 weeks after enrolment

Primary Outcome Measures

Name	Time	Method
All-cause mortality in the first 24 weeks after initiation of ART	24 weeks

Secondary Outcome Measures

Name	Time	Method
Causes of death	24 weeks
HIV viral suppression	24 weeks
TB incidence rates after ART initiation	24 weeks
CD4 T cell absolute increase	24 weeks
Safety and tolerability of anti-tuberculous medications	24 weeks

Trial Locations

Locations (3)

Infectious Diseases Institute University Makarere; 🇺🇬 Kampala, Uganda

Medical Research Unit, Albert Schweitzer Hospital; 🇬🇦 Lambaréné, Gabon

Ministry of Health -Provincial Heatlh Directorate of the Sofala Province (Direcção Provincial de Saúde de Sofala DPSS); 🇲🇿 Beira, Mozambique