The Safety and Effectiveness of Rifabutin, Combined With Clarithromycin or Azithromycin, in HIV-Infected Patients
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| ClinicalTrials.gov Identifier: NCT00001023 |
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Recruitment Status :
Completed
First Posted : August 31, 2001
Last Update Posted : October 31, 2012
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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 or disease | Intervention/treatment | Phase |
|---|---|---|
| Mycobacterium Avium-intracellulare Infection HIV Infections | Drug: Clarithromycin Drug: Azithromycin Drug: Rifabutin | Not Applicable |
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.
| Study Type : | Interventional (Clinical Trial) |
| Enrollment : | 91 participants |
| Allocation: | Randomized |
| Primary Purpose: | Treatment |
| Official Title: | Evaluation of the Safety, Tolerance and Pharmacokinetics of Rifabutin/Clarithromycin Combination and Rifabutin/Azithromycin Combination in HIV-Infected Patients |
| Actual Study Completion Date : | July 1998 |
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00001023
| 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 | |
| Study Chair: | R Hafner | ||
| Study Chair: | H Standiford |
| Responsible Party: | National Institute of Allergy and Infectious Diseases (NIAID) |
| ClinicalTrials.gov Identifier: | NCT00001023 |
| Other Study ID Numbers: |
DATRI 001 11732 ( Registry Identifier: DAIDS ES Registry Number ) |
| First Posted: | August 31, 2001 Key Record Dates |
| Last Update Posted: | October 31, 2012 |
| Last Verified: | October 2012 |
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Rifabutin Mycobacterium avium-intracellulare Infection Drug Interactions Azithromycin Clarithromycin |
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Infection Communicable Diseases Mycobacterium Infections Mycobacterium avium-intracellulare Infection Actinomycetales Infections Gram-Positive Bacterial Infections Bacterial Infections Mycobacterium Infections, Nontuberculous Azithromycin Clarithromycin |
Rifabutin Anti-Bacterial Agents Anti-Infective Agents Protein Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors Antibiotics, Antitubercular Antitubercular Agents |