Prevention of Early Mortality by Presumptive Tuberculosis (TB) Treatment (PrOMPT)
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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.
Condition | Intervention | Phase |
---|---|---|
HIV Infection Tuberculosis |
Drug: Experimental: Empiric TB treatment Drug: ART only arm |
Phase 4 |
Study Type: | Interventional |
Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
Official Title: | Prevention of Early Mortality by Presumptive TB Treatment in HIV-infected Patients Initiating Antiretroviral Therapy |
- All-cause mortality in the first 24 weeks after initiation of ART [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- CD4 T cell absolute increase [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
- Causes of death [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- Safety and tolerability of anti-tuberculous medications [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
- HIV viral suppression [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- TB incidence rates after ART initiation [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Estimated Enrollment: | 334 |
Study Start Date: | August 2011 |
Estimated Study Completion Date: | June 2014 |
Estimated Primary Completion Date: | June 2014 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
---|---|
Experimental: Empiric TB treatment
Empiric 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
|
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
|
Active Comparator: ART only arm
ART (efavirenz-based) only (+ pyridoxine 50mg) given within 2 weeks after enrolment
|
Drug: ART only arm
ART (efavirenz-based) only (+ pyridoxine 50mg) given within 2 weeks after enrolment
|
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
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)
Contact: Haniphaa Kakooza | h.kakooza@interact-ug.org | |
Contact: Nadine Pakker | +31 20 566 7800 | n.pakker@amc-cpcd.org |
Gabon | |
Medical Research Unit, Albert Schweitzer Hospital | Not yet recruiting |
Lambaréné, Gabon | |
Contact: AFSATOU NDAMA TRAORE, Dr (MSc, PhD) + 241 07 07 73 53 traoresafi@hotmail.com | |
Principal Investigator: AFSATOU NDAMA TRAORE, Dr (MSc, PhD) | |
Mozambique | |
Ministry of Health -Provincial Heatlh Directorate of the Sofala Province (Direcção Provincial de Saúde de Sofala DPSS) | Not yet recruiting |
Beira, Mozambique | |
Contact: Isaias Ramiro Manuel +258 23 325 235 dpss@gmail.com | |
Principal Investigator: Isaias Ramiro Manuel | |
South Africa | |
University of Limpopo Medunsa Campus | Not yet recruiting |
Pretoria, South Africa, 0204 | |
Contact: Zinhle MAKATINI +27 125213037 zinhle@wol.co.za | |
Principal Investigator: Zinhle MAKATINI | |
Uganda | |
Infectious Diseases Institute University Makarere | Not yet recruiting |
Kampala, Uganda | |
Contact: Yuka Manabe | |
Principal Investigator: Yuka Manabe |
Study Director: | Frank Cobelens | Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) |
Principal Investigator: | Yuka Manabe | Infectious Diseases Institute at Makerere University |
Additional Information:
No publications provided
Responsible Party: | Remko van Leeuwen, Director Clinical Operations, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) |
ClinicalTrials.gov Identifier: | NCT01417988 History of Changes |
Other Study ID Numbers: | AIGHD_001 |
Study First Received: | July 25, 2011 |
Last Updated: | August 15, 2011 |
Health Authority: | South Africa: Medicines Control Council Mozambique: Ministry of Health (MISAU) Gabon: Ministry of Health Uganda: Ministry of Health Uganda: National Council for Science and Technology Uganda: National Drug Authority |
Keywords provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
TB |
Additional relevant MeSH terms:
HIV Infections Acquired Immunodeficiency Syndrome Tuberculosis Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral |
Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Slow Virus Diseases Mycobacterium Infections Actinomycetales Infections Gram-Positive Bacterial Infections Bacterial Infections |
ClinicalTrials.gov processed this record on March 03, 2013