Tuberculosis Prevention for HIV Infected Adults

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Richard Chaisson, National Institute of Allergy and Infectious Disease (NIAID)
ClinicalTrials.gov Identifier:
NCT00057122
First received: March 27, 2003
Last updated: October 19, 2012
Last verified: October 2012

March 27, 2003
October 19, 2012
September 2002
November 2008   (final data collection date for primary outcome measure)
Development of confirmed, probable, or possible active pulmonary or extrapulmonary tuberculosis (TB) [ Time Frame: 6/2008 ] [ Designated as safety issue: No ]
Development of confirmed, probable, or possible active pulmonary or extrapulmonary TB
Complete list of historical versions of study NCT00057122 on ClinicalTrials.gov Archive Site
  • Risk of TB and death [ Time Frame: 6/2008 ] [ Designated as safety issue: No ]
  • rates of adherence, adverse reactions and treatment discontinuation [ Time Frame: 6/2008 ] [ Designated as safety issue: No ]
  • patterns of antibiotic resistance [ Time Frame: 6/2008 ] [ Designated as safety issue: No ]
  • clinical and epidemiological factors associated with developing TB [ Time Frame: 6/2008 ] [ Designated as safety issue: No ]
  • Proportion in each arm who have excellent adherence
  • proportion in each arm who have Grade 2, 3, or 4 drug-related toxicity to study medications
  • proportion in each arm who have discontinued therapy for any reason
  • proportion in each arm who have Mycobacterium tuberculosis isolates among subjects in each arm that are resistant to study medications
  • death
Not Provided
Not Provided
 
Tuberculosis Prevention for HIV Infected Adults
Novel TB Prevention Regimens for HIV-Infected Adults

This study compares three different tuberculosis (TB) prevention regimens against the standard regimen of 6 months of isoniazid. It is being conducted in Soweto, South Africa. People who are HIV positive and have a positive tuberculin skin test without signs of active tuberculosis may join.

AIDS is the leading cause of death in sub-Saharan Africa, and TB is the leading cause of death in patients with AIDS on that continent. Preventive therapy for HIV infected people with latent TB infection is important to reduce the risk of progression to active TB. Although preventive TB therapy is generally recommended throughout the Western world for people with HIV, it is not routinely advocated or provided to patients in developing countries. Six months of self-supervised INH is the gold standard of preventive TB therapy. Newer preventive regimens with a shorter duration of treatment and intermittent dosing could improve compliance and permit treatment supervision through dosing observation. This study will compare the standard INH regimen with two new regimens: rifapentine and INH observed once weekly for 12 weeks and rifampin and INH observed twice weekly for 12 weeks.

Patients will be interviewed to identify risk factors for TB and symptoms of active TB. A physical examination and chest radiograph will be performed on all potential patients to identify and exclude all active TB cases (these patients will be referred for appropriate treatment of their infection).

Patients who meet the inclusion criteria will be randomized to one of the following treatment arms: rifapentine/INH for 12 weeks, observed weekly; rifampin/INH for 12 weeks, observed twice weekly; INH for 6 months, self-supervised; or continuous INH, self-supervised. Patients randomized to the two self-administered INH arms will be given a 1 month supply of INH and instructed to take one pill each day. Patients in the continuous INH arm will take INH continuously until the end of the study. Depending on when the patient enrolls in the study, the patient could take INH for 1 to 4 years. Each patient will be provided with education on the need to adhere to the protocol and information on potential study drug related toxicity. All patients will be given their first dose of study medication during the enrollment period. Patients in the shorter-course, observed regimens will be given each of their doses in a clinic under the supervision of a study nurse.

At each study encounter, possible toxicity will be assessed via interview. Patients will be followed every 6 months after the completion of preventive therapy until the study closes. Outreach workers will perform home visits to encourage follow-up and determine vital status for any patient who has missed a scheduled follow-up visit. Patients with evidence of active tuberculosis at any follow-up visit will be evaluated and treated appropriately. Patients will be offered a small incentive for fulfilling study requirements. The equivalent of $5 (30 rand) will be paid after successful entry into the trial and at each 6 month visit as compensation for time spent in the study and to cover travel expenses.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
  • HIV Infections
  • Tuberculosis
  • Drug: Isoniazid
    300mg
  • Drug: Rifapentine
    Rifapentine 900 mg
  • Drug: Rifampin
    Rifampin 600 mg
  • Active Comparator: 1
    Interventions:
    • Drug: Isoniazid
    • Drug: Rifapentine
  • Active Comparator: 2
    Interventions:
    • Drug: Isoniazid
    • Drug: Rifampin
  • Active Comparator: 3
    Intervention: Drug: Isoniazid
  • Active Comparator: 4
    Intervention: Drug: Isoniazid
Martinson NA, Barnes GL, Moulton LH, Msandiwa R, Hausler H, Ram M, McIntyre JA, Gray GE, Chaisson RE. New regimens to prevent tuberculosis in adults with HIV infection. N Engl J Med. 2011 Jul 7;365(1):11-20.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1148
June 2009
November 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • HIV infected
  • Tuberculin test (PPD) positive 5 mm or greater
  • Chest x-ray negative for pulmonary tuberculosis

Exclusion Criteria:

  • Pregnant or breastfeeding
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
South Africa
 
NCT00057122
1R01AI48526-01A1, 5RO1AI048526-02
Not Provided
Richard Chaisson, National Institute of Allergy and Infectious Disease (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Not Provided
Principal Investigator: Richard Chaisson, MD Johns Hopkins Medical Institute
National Institute of Allergy and Infectious Diseases (NIAID)
October 2012

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