The Safety and Effectiveness of Rifabutin, Combined With Clarithromycin or Azithromycin, in HIV-Infected Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001023
First received: November 2, 1999
Last updated: October 29, 2012
Last verified: October 2012
  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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Primary Purpose: Treatment
Official Title: Evaluation of the Safety, Tolerance and Pharmacokinetics of Rifabutin/Clarithromycin Combination and Rifabutin/Azithromycin Combination in HIV-Infected Patients

Resource links provided by NLM:


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

Estimated Enrollment: 91
Study Completion Date: July 1998
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
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: NCT00001023

Locations
United States, Arizona
Univ of Arizona / Health Science Ctr
Tucson, Arizona, United States, 85724
United States, California
Palo Alto Veterans Affairs Health Care System
Palo Alto, California, United States, 94304
Davies Med Ctr
San Francisco, California, United States, 94114
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

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001023     History of Changes
Other Study ID Numbers: DATRI 001, 11732
Study First Received: November 2, 1999
Last Updated: October 29, 2012
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

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Mycobacterium Infections
Mycobacterium avium-intracellulare Infection
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Mycobacterium Infections, Atypical
Azithromycin
Clarithromycin
Rifabutin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antitubercular
Antitubercular Agents

ClinicalTrials.gov processed this record on July 20, 2014