NCT01417988

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.

Trial Health

60
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
44

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Aug 2011

Geographic Reach
3 countries

3 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 25, 2011

Completed
7 days until next milestone

Study Start

First participant enrolled

August 1, 2011

Completed
15 days until next milestone

First Posted

Study publicly available on registry

August 16, 2011

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2013

Completed
Last Updated

February 17, 2014

Status Verified

February 1, 2014

Enrollment Period

1.8 years

First QC Date

July 25, 2011

Last Update Submit

February 14, 2014

Conditions

HIV InfectionTuberculosis

Keywords

TB

Outcome Measures

Primary Outcomes (1)

  • All-cause mortality in the first 24 weeks after initiation of ART

    24 weeks

Secondary Outcomes (5)

  • CD4 T cell absolute increase

    24 weeks

  • Causes of death

    24 weeks

  • Safety and tolerability of anti-tuberculous medications

    24 weeks

  • HIV viral suppression

    24 weeks

  • TB incidence rates after ART initiation

    24 weeks

Study Arms (2)

Empiric TB treatment

EXPERIMENTAL

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

ART only arm

ACTIVE COMPARATOR

ART (efavirenz-based) only (+ pyridoxine 50mg) given within 2 weeks after enrolment

Drug: ART only arm

Interventions

Experimental: Empiric TB treatmentDRUG

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

Empiric TB treatment
ART only armDRUG

ART (efavirenz-based) only (+ pyridoxine 50mg) given within 2 weeks after enrolment

ART only arm

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Aged \> 18 years old
  • HIV-1 positive
  • Eligible for antiretroviral treatment with CD4 T cell count \< 50 cells/μl
  • BMI \< 18

You may not qualify if:

  • 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 the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Medical Research Unit, Albert Schweitzer Hospital

Lambaréné, Gabon

Location

Ministry of Health -Provincial Heatlh Directorate of the Sofala Province (Direcção Provincial de Saúde de Sofala DPSS)

Beira, Mozambique

Location

Infectious Diseases Institute University Makarere

Kampala, Uganda

Location

Related Links

MeSH Terms

Conditions

HIV InfectionsTuberculosis

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System DiseasesMycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and Mycoses

Study Officials

  • Frank Cobelens

    Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

    STUDY DIRECTOR

  • Yuka Manabe

    Infectious Diseases Institute at Makerere University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Executive Scientific Director AIGHD

Study Record Dates

First Submitted

July 25, 2011

First Posted

August 16, 2011

Study Start

August 1, 2011

Primary Completion

June 1, 2013

Study Completion

June 1, 2013

Last Updated

February 17, 2014

Record last verified: 2014-02

Locations

UG(1)GA(1)MO(1)