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The Safety and Effectiveness of Rifabutin, Combined With Clarithromycin or Azithromycin, in HIV-Infected Patients
This study has been completed.
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001023
  Purpose

PER 03/10/94 AMENDMENT: PART B. To determine whether there is an effect on plasma drug levels of azithromycin and rifabutin as measured by changes in the plasma concentration-time curve (AUC) when these drugs are taken concomitantly.

ORIGINAL PRIMARY: To gain preliminary information about the safety and tolerance of clarithromycin and azithromycin in combination with rifabutin (three potential agents against Mycobacterium avium-intracellulare) in HIV-infected patients with CD4 counts < 200 cells/mm3.

ORIGINAL SECONDARY: To determine whether there is an effect on the pharmacokinetics of the macrolide antibiotics or rifabutin when these drugs are taken concomitantly. To monitor the effect of rifabutin therapy on dapsone serum levels in patients taking dapsone for PCP prophylaxis. To monitor the effect of macrolide/rifabutin combination therapies on AZT or ddI serum levels.

Two new macrolide antibiotics, clarithromycin and azithromycin, and rifabutin (a rifamycin derivative) have all demonstrated in vitro and in vivo activity against Mycobacterium avium-intracellulare, a common systemic bacterial infection complicating AIDS. Further information is needed, however, regarding the clinical and pharmacokinetic interaction of these drugs used in combination.


Condition Intervention
Mycobacterium Avium-Intracellulare Infection
HIV Infections
Drug: Clarithromycin
Drug: Azithromycin
Drug: Rifabutin

MedlinePlus related topics: AIDS Antibiotics
Drug Information available for: Rifabutin Azithromycin Clarithromycin
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Safety Study
Official Title: Evaluation of the Safety, Tolerance and Pharmacokinetics of Rifabutin/Clarithromycin Combination and Rifabutin/Azithromycin Combination in HIV-Infected Patients

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

Estimated Enrollment: 91
Detailed Description:

Two new macrolide antibiotics, clarithromycin and azithromycin, and rifabutin (a rifamycin derivative) have all demonstrated in vitro and in vivo activity against Mycobacterium avium-intracellulare, a common systemic bacterial infection complicating AIDS. Further information is needed, however, regarding the clinical and pharmacokinetic interaction of these drugs used in combination.

AMENDED 03/10/94 (Part B): Approximately 38 HIV-infected or uninfected subjects are randomized to receive azithromycin or rifabutin (Groups 3 and 4) daily for 14 days, followed by a combination regimen of both drugs for 4 additional weeks. Patients are followed weekly. Pharmacokinetic sampling will be performed on days 14, 15, and 42-45.

ORIGINAL: Sixty-eight patients are randomly assigned to one of four groups (17 patients per group). They receive either clarithromycin or azithromycin in combination with rifabutin on one of two different dosing schedules. Patients receive medication for 6 weeks and undergo follow-up weekly during drug administration and at week 8.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Primary or secondary PCP prophylaxis with TMP/SMX, dapsone, or aerosolized pentamidine.
  • Any approved therapy for antiretroviral treatment, or antiretroviral therapy available through FDA-sanctioned treatment IND or treatment protocol.

Patients must have:

AMENDED (PART B):

  • Either HIV infection OR no HIV infection.
  • CD4 count unspecified.

ORIGINAL:

  • Documented HIV infection.
  • CD4 count < 200 cells/mm3 within 90 days prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

  • Known Mycobacterium avium-intracellulare (MAI) bacteremia or presence of a clinical syndrome compatible with MAI (i.e., fevers, weight loss, elevated LDH and alkaline phosphatase).
  • Fever = or > 38.5 deg C (100.4 deg F) within 7 days prior to study entry.

Concurrent Medication:

Excluded:

  • Acute or chronic use of phenobarbital, carbamazepine, rifampin, dilantin, fluconazole, itraconazole, ketoconazole, ciprofloxacin, beta-blockers, or clarithromycin.
  • Oral contraceptives.
  • Acute therapy for an AIDS-related opportunistic infection or malignancy, or other acute medical illness, or infection.
  • Maintenance therapy for CMV, cryptococcal meningitis, or toxoplasmosis.
  • Cytotoxic chemotherapy.

Patients with the following prior conditions are excluded:

  • History of intolerance or hypersensitivity to study drugs, other macrolide antibiotics, or rifampin.
  • Three or more loose bowel movements per day within 3 months prior to study entry.
  • Unintentional weight loss >= 5 percent of body weight within 3 months prior to study entry.

Prior Medication:

Excluded:

  • Rifabutin within 30 days prior to study entry.
  • Clarithromycin or azithromycin within 14 days prior to study entry.
  • Acute therapy for an AIDS-related opportunistic infection or malignancy, or other acute medical illness, or infection within 28 days prior to study entry.

Prior Treatment:

Excluded:

  • Blood transfusions within 1 month prior to study entry.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00001023

Locations
United States, Arizona
Univ of Arizona / Health Science Ctr
Tucson, Arizona, United States, 85724
United States, California
Davies Med Ctr
San Francisco, California, United States, 94114
Palo Alto Veterans Affairs Health Care System
Palo Alto, California, United States, 94304
United States, Colorado
Denver Public Health Dept
Denver, Colorado, United States, 802044507
United States, District of Columbia
Georgetown Univ Med Ctr
Washington, District of Columbia, United States, 20007
United States, Louisiana
Tulane Univ Med School
New Orleans, Louisiana, United States, 701122699
United States, Maryland
Univ of Maryland at Baltimore / Veterans Adm
Baltimore, Maryland, United States, 21201
United States, Missouri
Washington Univ School of Medicine
St Louis, Missouri, United States, 63108
United States, North Carolina
Univ of North Carolina School of Medicine
Chapel Hill, North Carolina, United States, 275997215
United States, Rhode Island
Univ of Rhode Island / Roger Williams Med Ctr
Providence, Rhode Island, United States, 02908
United States, Virginia
Med College of Virginia / School of Pharmacy
Richmond, Virginia, United States, 232980533
Sponsors and Collaborators
Investigators
Study Chair: R Hafner
Study Chair: H Standiford
  More Information

Click here for more information about Rifabutin  This link exits the ClinicalTrials.gov site
Click here for more information about Clarithromycin  This link exits the ClinicalTrials.gov site
Click here for more information about Azithromycin  This link exits the ClinicalTrials.gov site

Publications:
Study ID Numbers: DATRI 001
Study First Received: November 2, 1999
Last Updated: July 30, 2008
ClinicalTrials.gov Identifier: NCT00001023  
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Rifabutin
Mycobacterium avium-intracellulare Infection
Drug Interactions
Azithromycin
Clarithromycin

Study placed in the following topic categories:
Bacterial Infections
Sexually Transmitted Diseases, Viral
Rifabutin
Acquired Immunodeficiency Syndrome
Immunologic Deficiency Syndromes
Mycobacterium Infections, Atypical
Mycobacterium avium-intracellulare Infection
Virus Diseases
Clarithromycin
Gram-Positive Bacterial Infections
HIV Infections
Azithromycin
Sexually Transmitted Diseases
Mycobacterium Infections
Mycobacterium avium complex infection
Retroviridae Infections

Additional relevant MeSH terms:
Communicable Diseases
Anti-Infective Agents
RNA Virus Infections
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Enzyme Inhibitors
Infection
Actinomycetales Infections
Pharmacologic Actions
Antibiotics, Antitubercular
Anti-Bacterial Agents
Protein Synthesis Inhibitors
Therapeutic Uses
Lentivirus Infections
Antitubercular Agents

ClinicalTrials.gov processed this record on January 15, 2009