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

Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Mycobacterium Avium-intracellulare Infection; HIV Infections

Intervention: Clarithromycin (Drug); Azithromycin (Drug); Rifabutin (Drug)

Phase: N/A

Status: Completed

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
R Hafner, Study Chair
H Standiford, Study Chair

Summary

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.

Clinical Details

Official title: Evaluation of the Safety, Tolerance and Pharmacokinetics of Rifabutin/Clarithromycin Combination and Rifabutin/Azithromycin Combination in HIV-Infected Patients

Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Primary Purpose: Treatment

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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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.

Locations and Contacts

Univ of Arizona / Health Science Ctr, Tucson, Arizona 85724, United States

Palo Alto Veterans Affairs Health Care System, Palo Alto, California 94304, United States

Davies Med Ctr, San Francisco, California 94114, United States

Denver Public Health Dept, Denver, Colorado 802044507, United States

Georgetown Univ Med Ctr, Washington, District of Columbia 20007, United States

Tulane Univ Med School, New Orleans, Louisiana 701122699, United States

Univ of Maryland at Baltimore / Veterans Adm, Baltimore, Maryland 21201, United States

Washington Univ School of Medicine, St Louis, Missouri 63108, United States

Univ of North Carolina School of Medicine, Chapel Hill, North Carolina 275997215, United States

Univ of Rhode Island / Roger Williams Med Ctr, Providence, Rhode Island 02908, United States

Med College of Virginia / School of Pharmacy, Richmond, Virginia 232980533, United States

Additional Information

Click here for more information about Azithromycin

Related publications:

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.


Last updated: October 29, 2012

Page last updated: August 23, 2015

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