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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
  Purpose

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

Resource links provided by NLM:


Further study details as provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Primary Outcome Measures:
  • All-cause mortality in the first 24 weeks after initiation of ART [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 44
Study Start Date: August 2011
Study Completion Date: June 2013
Primary Completion Date: June 2013 (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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01417988

Locations
Gabon
Medical Research Unit, Albert Schweitzer Hospital
Lambaréné, Gabon
Mozambique
Ministry of Health -Provincial Heatlh Directorate of the Sofala Province (Direcção Provincial de Saúde de Sofala DPSS)
Beira, Mozambique
Uganda
Infectious Diseases Institute University Makarere
Kampala, Uganda
Sponsors and Collaborators
Prof JMA Lange
European and Developing Countries Clinical Trials Partnership (EDCTP)
Investigators
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:
No publications provided

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
Study First Received: July 25, 2011
Last Updated: February 14, 2014
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:
Acquired Immunodeficiency Syndrome
HIV Infections
Tuberculosis
Actinomycetales Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Mycobacterium Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases

ClinicalTrials.gov processed this record on November 24, 2014