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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000636
First received: November 2, 1999
Last updated: September 28, 2013
Last verified: September 2013
  Purpose

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.


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

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
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: October 1997
Detailed Description:

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.

  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/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.

  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: NCT00000636

  Hide Study Locations
Locations
United States, California
Community Consortium / UCSF
San Francisco, California, United States, 94110
United States, Colorado
Denver CPCRA / Denver Public Hlth
Denver, Colorado, United States, 802044507
United States, Connecticut
Hill Health Corp
New Haven, Connecticut, United States, 06519
United States, Delaware
Wilmington Hosp / Med Ctr of Delaware
Wilmington, Delaware, United States, 19899
United States, District of Columbia
Veterans Administration Med Ctr / Regional AIDS Program
Washington, District of Columbia, United States, 20422
United States, Georgia
AIDS Research Consortium of Atlanta
Atlanta, Georgia, United States, 30308
United States, Illinois
AIDS Research Alliance - Chicago
Chicago, Illinois, United States, 60657
Chicago Dept of Health / Speciality STD Clinic
Chicago, Illinois, United States, 60605
United States, Louisiana
Louisiana Comm AIDS Rsch Prog / Tulane Univ Med
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins Univ / School of Hygiene & Public Health
Baltimore, Maryland, United States, 21205
Johns Hopkins Univ / Brazil
Baltimore, Maryland, United States, 21205
United States, Massachusetts
Boston Dept of Health and Hosps
Boston, Massachusetts, United States, 02118
United States, Michigan
Henry Ford Hosp
Detroit, Michigan, United States, 48202
Comprehensive AIDS Alliance of Detroit
Detroit, Michigan, United States, 48201
United States, New Jersey
Southern New Jersey AIDS Cln Trials / Dept of Med
Camden, New Jersey, United States, 08103
Lattimore Comprehensive Pulmonary Disease Clinic
Newark, New Jersey, United States, 07103
Saint Michael's Med Ctr
Newark, New Jersey, United States, 07102
North Jersey Community Research Initiative
Newark, New Jersey, United States, 07103
United States, New York
Bronx Lebanon Hosp Ctr
Bronx, New York, United States, 10456
Addiction Research and Treatment Corp
Brooklyn, New York, United States, 11201
Clinical Directors Network of Region II
New York, New York, United States, 10011
Beth Israel Med Ctr
New York, New York, United States, 10035
Harlem AIDS Treatment Group / Harlem Hosp Ctr
New York, New York, United States, 10037
United States, Pennsylvania
Philadelphia FIGHT
Philadelphia, Pennsylvania, United States, 19107
United States, Virginia
Richmond AIDS Consortium
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Investigators
Study Chair: Gordin F
Study Chair: Brown LS
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000636     History of Changes
Other Study ID Numbers: CPCRA 004, TB/PPD+, ACTG 177, 11556
Study First Received: November 2, 1999
Last Updated: September 28, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Tuberculosis
Isoniazid
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 20, 2014