The Treatment of Tuberculosis in HIV-Infected Patients

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00001033

Collaborator

(none)

650

Enrollment

Locations

54.2

Patients Per Site

Study Details

Study Description

Brief Summary

PER 5/30/95 AMENDMENT: To compare the combined rate of failure during therapy and relapse after therapy between two durations of intermittent therapy (6 versus 9 months) for the treatment of pulmonary tuberculosis (TB) in HIV-infected patients. To compare toxicity, survival, and development of resistance in these two regimens.

ORIGINAL: To compare the efficacy and safety of induction and continuation therapies for the treatment of pulmonary TB in HIV-infected patients who are either from areas with known high rates of resistance to one or more anti-TB drugs or from areas where TB is expected to be susceptible to commonly used anti-TB drugs.

PER 5/30/95 AMENDMENT: In HIV-negative patients, intermittent anti-TB therapy has been shown to be as effective as daily therapy, but the optimal duration of therapy in HIV-infected patients has not been established.

ORIGINAL: In some areas of the country, resistance to one or more of the drugs commonly used to treat TB has emerged. Thus, the need to test regimens containing a new drug exists. Furthermore, the optimal duration of anti-TB therapy for HIV-infected patients with TB needs to be determined.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections Tuberculosis	Drug: Ethambutol hydrochloride Drug: Isoniazid Drug: Pyrazinamide Drug: Pyridoxine hydrochloride Drug: Levofloxacin Drug: Rifampin	Phase 3

Detailed Description

PER 5/30/95 AMENDMENT: Patients who have received an acceptable induction regimen prior to study entry and have been found to be susceptible to isoniazid and rifampin with no pyrazinamide resistance are randomized to receive either isoniazid or rifampin plus vitamin B6 biweekly for 18 or 31 weeks. Patients are evaluated at months 1, 2, 4, 6, 8, and 10, and every 4 months thereafter. Minimum follow-up is 1.5 years.

ORIGINAL: In the induction phase, patients enrolled in "drug-susceptible" areas (defined as metropolitan areas with a resistance rate for isoniazid therapy of less than 10 percent) receive four drugs: isoniazid (plus pyridoxine), rifampin, pyrazinamide, and ethambutol. Patients enrolled in "drug-resistant" areas (resistance rate for isoniazid of 10 percent or higher) receive the four-drug regimen with or without a fifth drug, levofloxacin. After 8 weeks of induction, patients with multi-drug resistance are removed from study regimens; all other patients enter a continuation phase. Pansusceptible patients (showing susceptibility to all first-line anti-TB drugs) receive two study drugs for an additional 18 or 31 weeks; patients with isoniazid-resistant (or intolerant) TB receive two or three study drugs for an additional 44 weeks, while those with rifampin-resistant TB receive two or three study drugs for an additional 70 weeks. Patients are evaluated every 2 weeks in the induction phase and every 12 weeks in the continuation phase. Minimum follow-up is 2 years.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

The Treatment of Pulmonary Mycobacterium Tuberculosis in HIV Infection

Actual Study Completion Date :

Jul 1, 1997

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Patients must have:

INDUCTION PHASE (ELIMINATED PER 5/30/95 AMENDMENT).

HIV infection.
Diagnosis of pulmonary TB.

NOTE:

Patients from "susceptible" areas may be 13 years of age or older. Patients from "resistant" areas must be 18 years of age or older.

CONTINUATION PHASE.

Successful completion of induction phase and confirmation of TB by culture and susceptibility results.
Susceptibility to and tolerance of isoniazid and rifampin and no resistance to pyrazinamide.
HIV infection.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

Multi-drug resistance to at least isoniazid and rifampin or known to have had close contact with a person with known multi-drug resistant TB.
Known treatment-limiting reaction to any of the study drugs.
Other disorders or conditions for which the study drugs are contraindicated.

Concurrent Medication:

Excluded:

Other medications with anti-TB activity.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USC CRS	Los Angeles	California	United States	90033
2	Howard University Hosp., Div. of Infectious Diseases, ACTU	Washington	District of Columbia	United States	20059
3	Univ. of Miami AIDS CRS	Miami	Florida	United States	33136
4	Univ. of Hawaii at Manoa, Leahi Hosp.	Honolulu	Hawaii	United States	96816
5	Cook County Hosp. CORE Ctr.	Chicago	Illinois	United States	60612
6	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland	United States	21287
7	SUNY - Buffalo, Erie County Medical Ctr	Buffalo	New York	United States	14215
8	NY Univ. HIV/AIDS CRS	New York	New York	United States	10016
9	Cornell University A2201	New York	New York	United States	10021
10	Beth Israel Med. Ctr. (Mt. Sinai)	New York	New York	United States	10029
11	Univ. of Cincinnati CRS	Cincinnati	Ohio	United States	45267
12	Hosp. of the Univ. of Pennsylvania CRS	Philadelphia	Pennsylvania	United States	19104