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

This study has been terminated.
(Study was terminated prematurely due to insufficient enrolment.)
Sponsor:
Collaborator:
European and Developing Countries Clinical Trials Partnership (EDCTP)
Information provided by (Responsible Party):
Prof JMA Lange, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:
NCT01417988
First received: July 25, 2011
Last updated: February 14, 2014
Last verified: February 2014

July 25, 2011
February 14, 2014
August 2011
June 2013   (final data collection date for primary outcome measure)
All-cause mortality in the first 24 weeks after initiation of ART [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01417988 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Prevention of Early Mortality by Presumptive Tuberculosis (TB) Treatment
Prevention of Early Mortality by Presumptive TB Treatment in HIV-infected Patients Initiating Antiretroviral Therapy

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.

Not Provided
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV Infection
  • Tuberculosis
  • 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
  • Drug: ART only arm
    ART (efavirenz-based) only (+ pyridoxine 50mg) given within 2 weeks after enrolment
  • 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
    Intervention: Drug: Experimental: Empiric TB treatment
  • Active Comparator: ART only arm
    ART (efavirenz-based) only (+ pyridoxine 50mg) given within 2 weeks after enrolment
    Intervention: Drug: ART only arm
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
44
June 2013
June 2013   (final data collection date for primary outcome measure)

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)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Gabon,   Mozambique,   Uganda
 
NCT01417988
AIGHD_001
Yes
Prof JMA Lange, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
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
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP