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Prophylaxis Against Tuberculosis (TB) in Patients With Human Immunodeficiency Virus (HIV) Infection and Confirmed Latent Tuberculous Infection
This study is ongoing, but not recruiting participants.
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000636
  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

MedlinePlus related topics: AIDS Tuberculosis
Drug Information available for: Vitamin B 6 5-Hydroxy-6-methyl-3,4-pyridinedimethanol hydrochloride Pyridoxine Pyrazinamide Isoniazid Rifampin Ftivazide
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Parallel Assignment, Efficacy Study
Official Title: Prophylaxis Against Tuberculosis (TB) in Patients With Human Immunodeficiency Virus (HIV) Infection and Confirmed Latent Tuberculous Infection

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

Estimated Enrollment: 2000
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000636

  Show 25 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Gordin F
Study Chair: Brown LS
  More Information

Click here for more information about Rifampin  This link exits the ClinicalTrials.gov site
Click here for more information about Isoniazid  This link exits the ClinicalTrials.gov site

Publications:
Study ID Numbers: CPCRA 004, TB/PPD+, ACTG 177
Study First Received: November 2, 1999
Last Updated: August 22, 2008
ClinicalTrials.gov Identifier: NCT00000636  
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

Study placed in the following topic categories:
Bacterial Infections
Opportunistic Infections
Sexually Transmitted Diseases, Viral
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Pyrazinamide
Vitamin B 6
Immunologic Deficiency Syndromes
Virus Diseases
Rifampin
Gram-Positive Bacterial Infections
HIV Infections
AIDS-Related Opportunistic Infections
Sexually Transmitted Diseases
Mycobacterium Infections
Pyridoxine
Tuberculosis
Retroviridae Infections
Isoniazid

Additional relevant MeSH terms:
Antimetabolites
Communicable Diseases
Anti-Infective Agents
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Infection
Anti-Bacterial Agents
Therapeutic Uses
Vitamins
Micronutrients
Nucleic Acid Synthesis Inhibitors
RNA Virus Infections
Vitamin B Complex
Immune System Diseases
Antilipemic Agents
Growth Substances
Enzyme Inhibitors
Pharmacologic Actions
Actinomycetales Infections
Antibiotics, Antitubercular
Lentivirus Infections
Antitubercular Agents
Fatty Acid Synthesis Inhibitors
Leprostatic Agents

ClinicalTrials.gov processed this record on January 15, 2009