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

NCT ID: NCT00000638

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

1999-09-30

Brief Summary

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To evaluate and compare the safety and effectiveness of a one-year course of isoniazid (INH) versus a two-month course of rifampin plus pyrazinamide for the prevention of reactivation tuberculosis in individuals infected with both HIV and latent (inactive) Mycobacterium tuberculosis.

Current guidelines from the American Thoracic Society and the Centers for Disease Control recommend 6 to 12 months of INH for PPD (purified protein derivative)-positive individuals. Although the effectiveness of this treatment is not known for HIV-infected individuals, several studies using INH to prevent tuberculosis in presumably normal hosts have shown 60 to 80 percent effectiveness. Problems with this treatment include compliance, adverse reaction, and the possibility of not preventing disease due to tuberculosis organisms being resistant to INH. A two-month preventive treatment plan should help in increasing compliance. In addition, the use of two drugs (rifampin / pyrazinamide) may help overcome problems with drug resistance. If this study shows equal or greater effectiveness of the two-month rifampin / pyrazinamide treatment, it could alter the approach to tuberculosis prevention for both HIV-positive and HIV-negative individuals.

Detailed Description

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Current guidelines from the American Thoracic Society and the Centers for Disease Control recommend 6 to 12 months of INH for PPD (purified protein derivative)-positive individuals. Although the effectiveness of this treatment is not known for HIV-infected individuals, several studies using INH to prevent tuberculosis in presumably normal hosts have shown 60 to 80 percent effectiveness. Problems with this treatment include compliance, adverse reaction, and the possibility of not preventing disease due to tuberculosis organisms being resistant to INH. A two-month preventive treatment plan should help in increasing compliance. In addition, the use of two drugs (rifampin / pyrazinamide) may help overcome problems with drug resistance. If this study shows equal or greater effectiveness of the two-month rifampin / pyrazinamide treatment, it could alter the approach to tuberculosis prevention for both HIV-positive and HIV-negative individuals.

Patients are chosen by a random selection process to either the INH or the rifampin / pyrazinamide arm of the dose. Patients on the INH arm receive INH plus vitamin B6 (pyridoxine hydrochloride ) daily for 12 months. Patients on the other arm receive rifampin plus pyrazinamide for 60 days. Dosage of rifampin and pyrazinamide depends on weight of patient.

Conditions

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HIV Infections Tuberculosis

Keywords

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Tuberculosis Isoniazid Mycobacterium tuberculosis 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

PREVENTION

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.

Patients must have:

* HIV infection.
* Current or documented history of positive PPD skin test.
* Life expectancy of at least 6 months or, in the physician's opinion, patient has a reasonable chance of survival to end of study.

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.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

* Current active clinical tuberculosis, confirmed or suspected.
* History of sensitivity / intolerance to any study medication.
* Evidence of peripheral neuropathy, i.e., signs or symptoms of paresis, paresthesias, neuromotor abnormalities, or neurosensory deficits of grade 3 or worse.
* Unwilling or unable to have current therapy and/or concomitant medication changed to avoid serious interaction with study medication.
* Acute hepatitis.
* Unable to comply with the follow-up requirements of the protocol.

Concurrent Medication:

Excluded:

* Treatment with quinolones, fluoroquinolones, aminoglycosides, or other agents that have activity against Mycobacterium tuberculosis.
* Excluded as ongoing (i.e., continuous, chronic and/or recurring) treatment:
* Aminoglycosides such as amikacin, aminosalicylic acid salts (PAS), capreomycin, clofazimine, cycloserine, ethambutol, ethionamide, isoniazid (INH) if randomized to rifampin/pyrazinamide arm of study, kanamycin, pyrazinamide if randomized to INH arm of study, and quinolones and fluoroquinolones, i.e., rifabutin, rifampin (if randomized to INH arm of study), ciprofloxacin, levofloxacin, ofloxacin, streptomycin, and thiacetazone.

Prior Medication:

Excluded:

* More than 2 months of continuous treatment, after documentation of a positive PPD skin test, with agents that have known or potential antituberculous activity or any antimycobacterial medication for \> 1 month.

Patients may not have the following prior conditions:

* History of sensitivity / intolerance to any study medication.
* Unwilling or unable to comply with the follow-up requirements of the protocol.
Minimum Eligible Age

13 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoechst Marion Roussel

INDUSTRY

Sponsor Role collaborator

Lederle Laboratories

INDUSTRY

Sponsor Role collaborator

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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Chaisson R

Role: STUDY_CHAIR

Locations

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Univ of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Children's Hosp of Los Angeles

Los Angeles, California, United States

Site Status

Univ of Southern California / LA County USC Med Ctr

Los Angeles, California, United States

Site Status

Highland Gen Hosp / San Francisco Gen Hosp

Oakland, California, United States

Site Status

San Francisco Gen Hosp

San Francisco, California, United States

Site Status

Stanford at Kaiser / Kaiser Permanente Med Ctr

San Francisco, California, United States

Site Status

Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium

San Jose, California, United States

Site Status

San Mateo AIDS Program / Stanford Univ

Stanford, California, United States

Site Status

Stanford Univ Med Ctr

Stanford, California, United States

Site Status

Olive View Med Ctr

Sylmar, California, United States

Site Status

Harbor UCLA Med Ctr

Torrance, California, United States

Site Status

Yale Univ / New Haven

New Haven, Connecticut, United States

Site Status

HIV Ctr - District of Columbia Gen Hosp

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

Site Status

Whitman - Walker Clinic / Georgetown Univ Med Ctr

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

Site Status

Georgetown Univ Med Ctr

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

Site Status

Howard Univ

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

Site Status

Univ of Miami School of Medicine

Miami, Florida, United States

Site Status

Queens Med Ctr

Honolulu, Hawaii, United States

Site Status

Univ of Hawaii

Honolulu, Hawaii, United States

Site Status

Children's Mem Hosp Family Cln / Northwestern Univ Med Schl

Chicago, Illinois, United States

Site Status

Northwestern Univ Med School

Chicago, Illinois, United States

Site Status

Rush Presbyterian - Saint Luke's Med Ctr

Chicago, Illinois, United States

Site Status

Louis A Weiss Memorial Hosp

Chicago, Illinois, United States

Site Status

Indiana Univ Hosp

Indianapolis, Indiana, United States

Site Status

State of MD Div of Corrections / Johns Hopkins Univ Hosp

Baltimore, Maryland, United States

Site Status

Johns Hopkins Hosp

Baltimore, Maryland, United States

Site Status

Beth Israel Deaconess - West Campus

Boston, Massachusetts, United States

Site Status

Baystate Med Ctr of Springfield

Springfield, Massachusetts, United States

Site Status

St Louis Regional Hosp / St Louis Regional Med Ctr

St Louis, Missouri, United States

Site Status

Univ of Nebraska Med Ctr

Omaha, Nebraska, United States

Site Status

Univ of Medicine & Dentistry of New Jersey / Univ Hosp

Newark, New Jersey, United States

Site Status

Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl

Newark, New Jersey, United States

Site Status

Adirondack Med Ctr at Saranac Lake

Albany, New York, United States

Site Status

Albany Med College / Division of HIV Medicine A158

Albany, New York, United States

Site Status

Mid - Hudson Care Ctr

Albany, New York, United States

Site Status

Interfaith Med Ctr

Brooklyn, New York, United States

Site Status

SUNY / Health Sciences Ctr at Brooklyn

Brooklyn, New York, United States

Site Status

SUNY / Erie County Med Ctr at Buffalo

Buffalo, New York, United States

Site Status

Nassau County Med Ctr

East Meadow, New York, United States

Site Status

City Hosp Ctr at Elmhurst / Mount Sinai Hosp

Elmhurst, New York, United States

Site Status

North Shore Univ Hosp

Manhasset, New York, United States

Site Status

Beth Israel Med Ctr

New York, New York, United States

Site Status

Bellevue Hosp / New York Univ Med Ctr

New York, New York, United States

Site Status

Saint Clare's Hosp and Health Ctr

New York, New York, United States

Site Status

Cornell Univ Med Ctr

New York, New York, United States

Site Status

Saint Luke's - Roosevelt Hosp Ctr

New York, New York, United States

Site Status

Mount Sinai Med Ctr

New York, New York, United States

Site Status

Columbia Presbyterian Med Ctr

New York, New York, United States

Site Status

SUNY - Stony Brook

Stony Brook, New York, United States

Site Status

SUNY / State Univ of New York

Syracuse, New York, United States

Site Status

Bronx Municipal Hosp Ctr/Jacobi Med Ctr

The Bronx, New York, United States

Site Status

Comprehensive Health Care Ctr / Bronx Municipal Hosp

The Bronx, New York, United States

Site Status

Montefiore Drug Treatment Ctr / Bronx Municipal Hosp

The Bronx, New York, United States

Site Status

Montefiore Family Health Ctr / Bronx Municipal Hosp

The Bronx, New York, United States

Site Status

Samaritan Village Inc / Bronx Municipal Hosp

The Bronx, New York, United States

Site Status

Jack Weiler Hosp / Bronx Municipal Hosp

The Bronx, New York, United States

Site Status

Montefiore Med Ctr / Bronx Municipal Hosp

The Bronx, New York, United States

Site Status

Montefiore Med Ctr Adolescent AIDS Program

The Bronx, New York, United States

Site Status

North Central Bronx Hosp / Bronx Municipal Hosp

The Bronx, New York, United States

Site Status

Univ of North Carolina

Chapel Hill, North Carolina, United States

Site Status

Moses H Cone Memorial Hosp

Greensboro, North Carolina, United States

Site Status

Wake County Dept of Health

Raleigh, North Carolina, United States

Site Status

Univ of Cincinnati

Cincinnati, Ohio, United States

Site Status

Univ of Kentucky Lexington

Cincinnati, Ohio, United States

Site Status

Case Western Reserve Univ

Cleveland, Ohio, United States

Site Status

MetroHealth Med Ctr

Cleveland, Ohio, United States

Site Status

Ohio State Univ Hosp Clinic

Columbus, Ohio, United States

Site Status

Girard Med Ctr

Philadelphia, Pennsylvania, United States

Site Status

Univ of Pennsylvania at Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Thomas Jefferson Univ Hosp

Philadelphia, Pennsylvania, United States

Site Status

Med Univ of South Carolina / UNC

Charleston, South Carolina, United States

Site Status

Julio Arroyo

West Columbia, South Carolina, United States

Site Status

Meharry Med College

Nashville, Tennessee, United States

Site Status

Univ of Texas Galveston

Galveston, Texas, United States

Site Status

Houston Clinical Research Network

Houston, Texas, United States

Site Status

Univ of Puerto Rico

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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Halsey N, et al. Twice weekly INH vs RIF and PZA for TB prophylaxis in HIV infected adults. Natl Conf Hum Retroviruses Relat Infect (2nd). 1995 Jan 29-Feb 2:55

Reference Type BACKGROUND

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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CPCRA 004

Identifier Type: -

Identifier Source: secondary_id

TB/PPD+

Identifier Type: -

Identifier Source: secondary_id

11152

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 177

Identifier Type: -

Identifier Source: org_study_id