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

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ClinicalTrials.gov Identifier: NCT01417988
Recruitment Status : Terminated (Study was terminated prematurely due to insufficient enrolment.)
First Posted : August 16, 2011
Last Update Posted : February 17, 2014
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment Phase
HIV Infection Tuberculosis Drug: Experimental: Empiric TB treatment Drug: ART only arm Phase 4

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prevention of Early Mortality by Presumptive TB Treatment in HIV-infected Patients Initiating Antiretroviral Therapy
Study Start Date : August 2011
Primary Completion Date : June 2013
Study Completion Date : June 2013

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :
  1. All-cause mortality in the first 24 weeks after initiation of ART [ Time Frame: 24 weeks ]

Secondary Outcome Measures :
  1. CD4 T cell absolute increase [ Time Frame: 24 weeks ]
  2. Causes of death [ Time Frame: 24 weeks ]
  3. Safety and tolerability of anti-tuberculous medications [ Time Frame: 24 weeks ]
  4. HIV viral suppression [ Time Frame: 24 weeks ]
  5. TB incidence rates after ART initiation [ Time Frame: 24 weeks ]

Eligibility Criteria

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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)
Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01417988

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
Infectious Diseases Institute University Makarere
Kampala, Uganda
Sponsors and Collaborators
Prof JMA Lange
European and Developing Countries Clinical Trials Partnership (EDCTP)
Study Director: Frank Cobelens Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Principal Investigator: Yuka Manabe Infectious Diseases Institute at Makerere University
More Information

Additional Information:
Responsible Party: Prof JMA Lange, Executive Scientific Director AIGHD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT01417988     History of Changes
Other Study ID Numbers: AIGHD_001
First Posted: August 16, 2011    Key Record Dates
Last Update Posted: February 17, 2014
Last Verified: February 2014

Keywords provided by Prof JMA Lange, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers