Prevention of Early Mortality by Presumptive Tuberculosis (TB) Treatment (PrOMPT)

Prof JMA Lange

Status and phase

Terminated

Phase 4

Conditions

Tuberculosis

HIV Infection

Treatments

Drug: ART only arm

Drug: Experimental: Empiric TB treatment

Study type

Interventional

Funder types

Other

Identifiers

NCT01417988

AIGHD_001

Details and patient eligibility

About

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.

Enrollment

44 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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)