Prevention of Early Mortality by Presumptive Tuberculosis (TB) Treatment

Tuberculosis Clinical Trial

— PrOMPT  

Official title:

Prevention of Early Mortality by Presumptive TB Treatment in HIV-infected Patients Initiating Antiretroviral Therapy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01417988
• Other study ID #: AIGHD_001
• Status: Terminated
• Phase: Phase 4
• First received: July 25, 2011
• Last updated: February 14, 2014
• Start date: August 2011
• Est. completion date: June 2013

Study information

• Verified date: February 2014
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Africa: Medicines Control CouncilMozambique: Ministry of Health (MISAU)Gabon: Ministry of HealthUganda: Ministry of HealthUganda: National Council for Science and TechnologyUganda: National Drug Authority
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 44
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infection
• Tuberculosis

Intervention

Drug:
• Experimental: Empiric TB treatment
Initiation of 4 drug TB treatment (8 weeks of 4 drug, 16 weeks of 2 drug therapy) followed by ART (efavirenz-based) within 2 weeks
• ART only arm
ART (efavirenz-based) only (+ pyridoxine 50mg) given within 2 weeks after enrolment

Locations

Country	Name	City	State
Gabon	Medical Research Unit, Albert Schweitzer Hospital	Lambaréné
Mozambique	Ministry of Health -Provincial Heatlh Directorate of the Sofala Province (Direcção Provincial de Saúde de Sofala DPSS)	Beira
Uganda	Infectious Diseases Institute University Makarere	Kampala

Sponsors (2)

Lead Sponsor	Collaborator
Prof JMA Lange	European and Developing Countries Clinical Trials Partnership (EDCTP)

Countries where clinical trial is conducted

Gabon,  Mozambique,  Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All-cause mortality in the first 24 weeks after initiation of ART		24 weeks	No
Secondary	CD4 T cell absolute increase		24 weeks	Yes
Secondary	Causes of death		24 weeks	No
Secondary	Safety and tolerability of anti-tuberculous medications		24 weeks	Yes
Secondary	HIV viral suppression		24 weeks	No
Secondary	TB incidence rates after ART initiation		24 weeks	No

External Links

•   Official Website of the sponsor