Prophylaxis Against Tuberculosis (TB) in Patients With Human Immunodeficiency Virus (HIV) Infection and Confirmed Latent Tuberculous Infection

NCT ID: NCT00000636

Last Updated: 2021-11-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

2000 participants

Study Classification

INTERVENTIONAL

Study Completion Date

1997-10-31

Brief Summary

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To evaluate and compare the effectiveness of a 2-month regimen of rifampin and pyrazinamide versus a 1-year course of isoniazid (INH) to prevent the development of tuberculosis in patients who are coinfected with HIV and latent Mycobacterium tuberculosis (MTb).

Current guidelines recommend 6 to 12 months of treatment with INH for purified protein derivative (PPD)-positive individuals. Problems with this treatment include compliance, adverse reaction, and the possibility of not preventing disease due to INH-resistant organisms. Studies suggest that two or three months of rifampin and pyrazinamide may be more effective than longer courses of INH. A two-month prevention course should help to increase compliance. In addition, the use of two drugs (rifampin and pyrazinamide) may help overcome problems with drug resistance.

Detailed Description

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Current guidelines recommend 6 to 12 months of treatment with INH for purified protein derivative (PPD)-positive individuals. Problems with this treatment include compliance, adverse reaction, and the possibility of not preventing disease due to INH-resistant organisms. Studies suggest that two or three months of rifampin and pyrazinamide may be more effective than longer courses of INH. A two-month prevention course should help to increase compliance. In addition, the use of two drugs (rifampin and pyrazinamide) may help overcome problems with drug resistance.

After baseline screening, patients are randomized to one of two treatment arms and are evaluated by means of clinic visits monthly for the first three months, then every three months for the first year (there are additional clinic visits for INH patients). Patients are then evaluated every six months. One group of patients takes INH plus vitamin B6 for 12 months. The other group of patients takes 1 of 2 doses of rifampin (depending on patient's weight) plus pyrazinamide in 3-4 divided doses for 60 days.

Conditions

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HIV Infections Tuberculosis

Keywords

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Tuberculosis Isoniazid Pyrazinamide Pyridoxine Rifampin AIDS-Related Opportunistic Infections Drug Therapy, Combination Acquired Immunodeficiency Syndrome Antitubercular Agents AIDS-Related Complex

Study Design

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Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Interventions

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Isoniazid

Intervention Type DRUG

Pyrazinamide

Intervention Type DRUG

Pyridoxine hydrochloride

Intervention Type DRUG

Rifampin

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Concurrent Medication:

Allowed:

* Antiretroviral treatment.
* Pneumocystis carinii pneumonia prophylaxis.
* Treatment for acute opportunistic infection/malignancy.
* Aminoglycosides, quinolones or fluoroquinolones such as ciprofloxacin or ofloxacin for \< 14 days for treatment of intercurrent infection.

Patients must have:

* HIV infection.
* Signed informed consent.
* Reasonably good health at time of study entry.
* Perceived life expectancy of at least six months.
* Allowed:
* Participation in other clinical trials as long as there is no potential activity of other study drugs against Mycobacterium tuberculosis (MTb), additive toxicities between study agents, or known possible drug interactions between study drugs.

Prior Medication:

Allowed:

* Treatment with quinolones, fluoroquinolones, aminoglycosides, or other agents with known or potential activity against M. tuberculosis.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

* Current active tuberculosis (confirmed or suspected).
* Sensitivity or intolerance to study medication.
* Acute hepatitis.
* Evidence of peripheral neuropathy, i.e., signs or symptoms of paresis, paresthesias, neuromotor abnormalities, or neurosensory deficits of grade 3 or worse.
* Inability to have concomitant medications changed to avoid serious interaction with study drug.

Concurrent Medication:

Excluded:

\-

Quinolones, fluoroquinolones, or aminoglycosides with antituberculous activity (may be used for up to 14 days for treatment of intercurrent infection).Other agents with known or potential antituberculous activity should be avoided, including the following:

* Aminosalicylic acid salts, capreomycin, clofazimine, cycloserine, ethambutol, ethionamide, isoniazid, kanamycin, pyrazinamide, rifabutin, rifampin, streptomycin, and thiacetazone.

Prior Medication:

Excluded:

* History of treatment for \> 2 months with agents that have known or potential antituberculous activity other than those specifically allowed.

Agents with potential or known antituberculous activity include the following:

* Aminoglycosides such as amikacin, aminosalicylic acid salts, capreomycin, ciprofloxacin, clofazimine, cycloserine, ethambutol, ethionamide, isoniazid, kanamycin, ofloxacin, pyrazinamide, quinolones or fluoroquinolones, rifabutin, rifampin, streptomycin, and thiacetazone.

Patients may not have:

* Current active tuberculosis.
* Acute hepatitis.
* Peripheral neuropathy of grade 3 or grade 4.

Willing and able, in the clinician's opinion, to comply with the treatment and clinical management issues.
Minimum Eligible Age

13 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gordin F

Role: STUDY_CHAIR

Brown LS

Role: STUDY_CHAIR

Locations

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Community Consortium / UCSF

San Francisco, California, United States

Site Status

Denver CPCRA / Denver Public Hlth

Denver, Colorado, United States

Site Status

Hill Health Corp

New Haven, Connecticut, United States

Site Status

Wilmington Hosp / Med Ctr of Delaware

Wilmington, Delaware, United States

Site Status

Veterans Administration Med Ctr / Regional AIDS Program

Washington D.C., District of Columbia, United States

Site Status

AIDS Research Consortium of Atlanta

Atlanta, Georgia, United States

Site Status

Chicago Dept of Health / Speciality STD Clinic

Chicago, Illinois, United States

Site Status

AIDS Research Alliance - Chicago

Chicago, Illinois, United States

Site Status

Louisiana Comm AIDS Rsch Prog / Tulane Univ Med

New Orleans, Louisiana, United States

Site Status

Johns Hopkins Univ / Brazil

Baltimore, Maryland, United States

Site Status

Johns Hopkins Univ / School of Hygiene & Public Health

Baltimore, Maryland, United States

Site Status

Boston Dept of Health and Hosps

Boston, Massachusetts, United States

Site Status

Comprehensive AIDS Alliance of Detroit

Detroit, Michigan, United States

Site Status

Henry Ford Hosp

Detroit, Michigan, United States

Site Status

Southern New Jersey AIDS Cln Trials / Dept of Med

Camden, New Jersey, United States

Site Status

Saint Michael's Med Ctr

Newark, New Jersey, United States

Site Status

Lattimore Comprehensive Pulmonary Disease Clinic

Newark, New Jersey, United States

Site Status

North Jersey Community Research Initiative

Newark, New Jersey, United States

Site Status

Addiction Research and Treatment Corp

Brooklyn, New York, United States

Site Status

Clinical Directors Network of Region II

New York, New York, United States

Site Status

Beth Israel Med Ctr

New York, New York, United States

Site Status

Harlem AIDS Treatment Group / Harlem Hosp Ctr

New York, New York, United States

Site Status

Bronx Lebanon Hosp Ctr

The Bronx, New York, United States

Site Status

Philadelphia FIGHT

Philadelphia, Pennsylvania, United States

Site Status

Richmond AIDS Consortium

Richmond, Virginia, United States

Site Status

Countries

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United States

References

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Gordin F, Matts J, Miller C, Chaisson R, Garcia M, O'Brien R. Risk factors for developing active tuberculosis (TB) among HIV-infected, PPD-positive (+) patients (pts). Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:151 (abstract no 448)

Reference Type BACKGROUND

New TB guidelines for persons with HIV. AIDS Treat News. 1998 Nov 6;(No 306):6.

Reference Type BACKGROUND
PMID: 11365963 (View on PubMed)

Gordin F, Chaisson RE, Matts JP, Miller C, de Lourdes Garcia M, Hafner R, Valdespino JL, Coberly J, Schechter M, Klukowicz AJ, Barry MA, O'Brien RJ. Rifampin and pyrazinamide vs isoniazid for prevention of tuberculosis in HIV-infected persons: an international randomized trial. Terry Beirn Community Programs for Clinical Research on AIDS, the Adult AIDS Clinical Trials Group, the Pan American Health Organization, and the Centers for Disease Control and Prevention Study Group. JAMA. 2000 Mar 15;283(11):1445-50. doi: 10.1001/jama.283.11.1445.

Reference Type BACKGROUND
PMID: 10732934 (View on PubMed)

Other Identifiers

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TB/PPD+

Identifier Type: -

Identifier Source: secondary_id

ACTG 177

Identifier Type: -

Identifier Source: secondary_id

11556

Identifier Type: REGISTRY

Identifier Source: secondary_id

CPCRA 004

Identifier Type: -

Identifier Source: org_study_id