Tuberculosis Prevention for HIV Infected Adults

NCT ID: NCT00057122

Last Updated: 2012-10-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1148 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-09-30
• Study Completion Date: 2009-06-30

Brief Summary

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.

Detailed Description

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.

Conditions

HIV Infections; Tuberculosis

Keywords

Preventive therapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

1

Group Type: ACTIVE_COMPARATOR

Isoniazid

Intervention Type: DRUG

300mg

Rifapentine

Intervention Type: DRUG

Rifapentine 900 mg

2

Group Type: ACTIVE_COMPARATOR

Isoniazid

Intervention Type: DRUG

300mg

Rifampin

Intervention Type: DRUG

Rifampin 600 mg

3

Group Type: ACTIVE_COMPARATOR

Isoniazid

Intervention Type: DRUG

300mg

4

Group Type: ACTIVE_COMPARATOR

Isoniazid

Intervention Type: DRUG

300mg

Interventions

Isoniazid

300mg

Intervention Type: DRUG

Rifapentine

Rifapentine 900 mg

Intervention Type: DRUG

Rifampin

Rifampin 600 mg

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• Pregnant or breastfeeding

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Richard Chaisson

Director, Center for TB Research

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Richard Chaisson, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins Medical Institute

Locations

Chris Hani Baragwanath Hospital

Soweto, , South Africa

Countries

South Africa

References

Singh P, Moulton LH, Barnes GL, Gupta A, Msandiwa R, Chaisson RE, Martinson NA. Pregnancy in Women With HIV in a Tuberculosis Preventive Therapy Trial. J Acquir Immune Defic Syndr. 2022 Dec 1;91(4):397-402. doi: 10.1097/QAI.0000000000003078.

Reference Type: DERIVED

PMID: 36000934 (View on PubMed)

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. doi: 10.1056/NEJMoa1005136.

Reference Type: DERIVED

PMID: 21732833 (View on PubMed)

Other Identifiers

5R01AI048526-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1R01AI048526-01A1

Identifier Type: NIH

Identifier Source: org_study_id

View Link