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

This study has been completed.
Sponsor:
Collaborators:
Hoechst Marion Roussel
Lederle Laboratories
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000638
First received: November 2, 1999
Last updated: March 29, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention
HIV Infections
Tuberculosis
Drug: Isoniazid
Drug: Pyrazinamide
Drug: Pyridoxine hydrochloride
Drug: Rifampin

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Primary Purpose: Prevention
Official Title: Prophylaxis Against Tuberculosis (TB) in Patients With Human Immunodeficiency Virus (HIV) Infection and Confirmed Latent Tuberculous Infection

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 2000
Study Completion Date: September 1999
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000638

  Hide Study Locations
Locations
United States, Alabama
Univ of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Univ of Southern California / LA County USC Med Ctr
Los Angeles, California, United States, 900331079
Children's Hosp of Los Angeles
Los Angeles, California, United States, 90027
Highland Gen Hosp / San Francisco Gen Hosp
Oakland, California, United States, 946021018
San Francisco Gen Hosp
San Francisco, California, United States, 941102859
Stanford at Kaiser / Kaiser Permanente Med Ctr
San Francisco, California, United States, 94115
Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
San Jose, California, United States, 951282699
Stanford Univ Med Ctr
Stanford, California, United States, 943055107
San Mateo AIDS Program / Stanford Univ
Stanford, California, United States, 943055107
Olive View Med Ctr
Sylmar, California, United States, 91342
Harbor UCLA Med Ctr
Torrance, California, United States, 90502
United States, Connecticut
Yale Univ / New Haven
New Haven, Connecticut, United States, 065102483
United States, District of Columbia
Howard Univ
Washington, District of Columbia, United States, 20059
Georgetown Univ Med Ctr
Washington, District of Columbia, United States, 20007
Whitman - Walker Clinic / Georgetown Univ Med Ctr
Washington, District of Columbia, United States, 200072197
HIV Ctr - District of Columbia Gen Hosp
Washington, District of Columbia, United States, 200072197
United States, Florida
Univ of Miami School of Medicine
Miami, Florida, United States, 331361013
United States, Hawaii
Queens Med Ctr
Honolulu, Hawaii, United States, 96816
Univ of Hawaii
Honolulu, Hawaii, United States, 96816
United States, Illinois
Rush Presbyterian - Saint Luke's Med Ctr
Chicago, Illinois, United States, 60612
Northwestern Univ Med School
Chicago, Illinois, United States, 60611
Children's Mem Hosp Family Cln / Northwestern Univ Med Schl
Chicago, Illinois, United States, 60611
Louis A Weiss Memorial Hosp
Chicago, Illinois, United States, 60640
United States, Indiana
Indiana Univ Hosp
Indianapolis, Indiana, United States, 462025250
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
State of MD Div of Corrections / Johns Hopkins Univ Hosp
Baltimore, Maryland, United States, 212052196
United States, Massachusetts
Beth Israel Deaconess - West Campus
Boston, Massachusetts, United States, 02215
Baystate Med Ctr of Springfield
Springfield, Massachusetts, United States, 01199
United States, Missouri
St Louis Regional Hosp / St Louis Regional Med Ctr
St Louis, Missouri, United States, 63112
United States, Nebraska
Univ of Nebraska Med Ctr
Omaha, Nebraska, United States, 681985130
United States, New Jersey
Univ of Medicine & Dentistry of New Jersey / Univ Hosp
Newark, New Jersey, United States, 071032714
Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl
Newark, New Jersey, United States, 071072198
United States, New York
Mid - Hudson Care Ctr
Albany, New York, United States, 122083479
Adirondack Med Ctr at Saranac Lake
Albany, New York, United States, 122083479
Albany Med College / Division of HIV Medicine A158
Albany, New York, United States, 122083479
Montefiore Family Health Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10461
Samaritan Village Inc / Bronx Municipal Hosp
Bronx, New York, United States, 10461
Montefiore Drug Treatment Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10461
Jack Weiler Hosp / Bronx Municipal Hosp
Bronx, New York, United States, 10465
Comprehensive Health Care Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10461
Bronx Municipal Hosp Ctr/Jacobi Med Ctr
Bronx, New York, United States, 10461
Montefiore Med Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10467
North Central Bronx Hosp / Bronx Municipal Hosp
Bronx, New York, United States, 10467
Montefiore Med Ctr Adolescent AIDS Program
Bronx, New York, United States, 10467
SUNY / Health Sciences Ctr at Brooklyn
Brooklyn, New York, United States, 112032098
Interfaith Med Ctr
Brooklyn, New York, United States, 112032098
SUNY / Erie County Med Ctr at Buffalo
Buffalo, New York, United States, 14215
Nassau County Med Ctr
East Meadow, New York, United States, 11554
City Hosp Ctr at Elmhurst / Mount Sinai Hosp
Elmhurst, New York, United States, 11373
North Shore Univ Hosp
Manhasset, New York, United States, 11030
Saint Clare's Hosp and Health Ctr
New York, New York, United States, 10019
Mount Sinai Med Ctr
New York, New York, United States, 10029
Cornell Univ Med Ctr
New York, New York, United States, 10021
Beth Israel Med Ctr
New York, New York, United States, 10003
Columbia Presbyterian Med Ctr
New York, New York, United States, 100323784
Saint Luke's - Roosevelt Hosp Ctr
New York, New York, United States, 10025
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
SUNY - Stony Brook
Stony Brook, New York, United States, 117948153
SUNY / State Univ of New York
Syracuse, New York, United States, 13210
United States, North Carolina
Univ of North Carolina
Chapel Hill, North Carolina, United States, 275997215
Moses H Cone Memorial Hosp
Greensboro, North Carolina, United States, 27401
Wake County Dept of Health
Raleigh, North Carolina, United States, 27610
United States, Ohio
Univ of Kentucky Lexington
Cincinnati, Ohio, United States, 45267
Univ of Cincinnati
Cincinnati, Ohio, United States, 452670405
MetroHealth Med Ctr
Cleveland, Ohio, United States, 441091998
Case Western Reserve Univ
Cleveland, Ohio, United States, 44106
Ohio State Univ Hosp Clinic
Columbus, Ohio, United States, 432101228
United States, Pennsylvania
Univ of Pennsylvania at Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Thomas Jefferson Univ Hosp
Philadelphia, Pennsylvania, United States, 191075098
Girard Med Ctr
Philadelphia, Pennsylvania, United States, 191046073
United States, South Carolina
Med Univ of South Carolina / UNC
Charleston, South Carolina, United States, 29425
Julio Arroyo
West Columbia, South Carolina, United States, 29169
United States, Tennessee
Meharry Med College
Nashville, Tennessee, United States, 37203
United States, Texas
Univ of Texas Galveston
Galveston, Texas, United States, 775550435
Houston Clinical Research Network
Houston, Texas, United States, 77266
Puerto Rico
Univ of Puerto Rico
San Juan, Puerto Rico, 009365067
Sponsors and Collaborators
Hoechst Marion Roussel
Lederle Laboratories
Investigators
Study Chair: Chaisson R
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000638     History of Changes
Other Study ID Numbers: ACTG 177, CPCRA 004, TB/PPD+, 11152
Study First Received: November 2, 1999
Last Updated: March 29, 2012
Health Authority: Unspecified

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Tuberculosis
Isoniazid
Mycobacterium tuberculosis
Pyrazinamide
Pyridoxine
Rifampin
AIDS-Related Opportunistic Infections
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
Antitubercular Agents
AIDS-Related Complex

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Tuberculosis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Antitubercular Agents
Isoniazid
Pyrazinamide
Rifampin
Pyridoxine
Vitamin B 6
Pyridoxal
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Fatty Acid Synthesis Inhibitors
Hypolipidemic Agents
Antimetabolites

ClinicalTrials.gov processed this record on August 28, 2014