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

NCT ID: NCT00001023

Last Updated: 2012-10-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

91 participants

Study Classification

INTERVENTIONAL

Study Completion Date

1998-07-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Mycobacterium Avium-intracellulare Infection HIV Infections

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Rifabutin Mycobacterium avium-intracellulare Infection Drug Interactions Azithromycin Clarithromycin

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Clarithromycin

Intervention Type DRUG

Azithromycin

Intervention Type DRUG

Rifabutin

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

R Hafner

Role: STUDY_CHAIR

H Standiford

Role: STUDY_CHAIR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Univ of Arizona / Health Science Ctr

Tucson, Arizona, United States

Site Status

Palo Alto Veterans Affairs Health Care System

Palo Alto, California, United States

Site Status

Davies Med Ctr

San Francisco, California, United States

Site Status

Denver Public Health Dept

Denver, Colorado, United States

Site Status

Georgetown Univ Med Ctr

Washington D.C., District of Columbia, United States

Site Status

Tulane Univ Med School

New Orleans, Louisiana, United States

Site Status

Univ of Maryland at Baltimore / Veterans Adm

Baltimore, Maryland, United States

Site Status

Washington Univ School of Medicine

St Louis, Missouri, United States

Site Status

Univ of North Carolina School of Medicine

Chapel Hill, North Carolina, United States

Site Status

Univ of Rhode Island / Roger Williams Med Ctr

Providence, Rhode Island, United States

Site Status

Med College of Virginia / School of Pharmacy

Richmond, Virginia, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Hafner R, Bethel J, Standiford HC, Follansbee S, Cohn DL, Polk RE, Mole L, Raasch R, Kumar P, Mushatt D, Drusano G; DATRI 001B Study Group. Tolerance and pharmacokinetic interactions of rifabutin and azithromycin. Antimicrob Agents Chemother. 2001 May;45(5):1572-7. doi: 10.1128/AAC.45.5.1572-1577.2001.

Reference Type BACKGROUND
PMID: 11302832 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

11732

Identifier Type: REGISTRY

Identifier Source: secondary_id

DATRI 001

Identifier Type: -

Identifier Source: org_study_id