A Comparison of Three Drug Combinations Containing Clarithromycin in the Treatment of Mycobacterium Avium Complex (MAC) Disease in Patients With AIDS
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Mycobacterium Avium-Intracellulare Infection; HIV Infections
Intervention: Indinavir sulfate (Drug); Ritonavir (Drug); Ethambutol hydrochloride (Drug); Clarithromycin (Drug); Rifabutin (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s):
Benson CA, Study Chair
Chaisson RE, Study Chair
Currier JS, Study Chair
Summary
To compare the efficacy and safety of clarithromycin combined with rifabutin, ethambutol, or
both in the treatment of disseminated Mycobacterium avium Complex (MAC) disease in persons
with AIDS, including individuals who have or have not received prior MAC prophylaxis.
It is believed that effective therapy for MAC disease in patients with AIDS requires
combinations of two or more antimycobacterial agents in order to overcome drug resistance and
the unfavorable influence of the profound immunosuppression associated with AIDS. Data
suggest that clarithromycin may have substantial activity in two- or three-drug combination
regimens with clofazimine, rifamycin derivatives, ethambutol, or the 4-quinolones.
Clinical Details
Official title: A Phase II/III Prospective, Multicenter, Randomized, Controlled Trial Comparing the Safety and Efficacy of Three Clarithromycin-Containing Combination Drug Regimens for the Treatment of Disseminated Mycobacterium Avium Complex (MAC) Disease in Persons With AIDS
Study design: Treatment, Safety Study
Detailed description:
It is believed that effective therapy for MAC disease in patients with AIDS requires
combinations of two or more antimycobacterial agents in order to overcome drug resistance and
the unfavorable influence of the profound immunosuppression associated with AIDS. Data
suggest that clarithromycin may have substantial activity in two- or three-drug combination
regimens with clofazimine, rifamycin derivatives, ethambutol, or the 4-quinolones.
Patients are randomized to one of three treatment arms containing clarithromycin in
combination with ethambutol, rifabutin, or both. Clarithromycin alone is taken on days 1
through 3 to determine tolerance and rifabutin and/or ethambutol is added on day 3. AS PER
AMENDMENT 7/2/97: Patients may elect to add ritonavir or indinavir to their treatment
regimen. Treatment continues daily for 48 weeks. In the absence of a dose-limiting toxicity,
those patients who are determined to be complete or partial responders continue on the
regimen to which they were originally assigned. Patients who have failed or relapsed on
originally assigned MAC therapy, must have their therapy amended to receive clarithromycin
and at least two other drugs not included in their originally assigned regimen. Patients are
followed twice in the first week, then every 2 weeks for the first 2 months, then monthly for
the next 4 months, and then every 2 months thereafter until the end of 12 months. PER
AMENDMENT 10/10/96: NOTE: Any patient who develops a toxicity to rifabutin or ethambutol
after week 12 or thereafter will be offered the option of being registered to a salvage
regimen of 2 new drugs not previously received, plus clarithromycin to continue for the study
duration.
Eligibility
Minimum age: 13 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria
Concurrent Medication:
Allowed:
- Antiretroviral therapy.
- Maintenance or prophylactic therapy for other opportunistic infections (with the
exception of specifically excluded drugs).
- Carbamazepine or theophylline.
- Isoniazid for TB prophylaxis.
PER AMENDMENT 10/10/96:
- Therapy for acute infectious processes, other than MAC, provided that the patient is
stable on the therapy.
- Fluconazole therapy for maintenance or suppression of fungal infections, providing the
patient has been on a stable dose for at least 4 weeks.
PER AMENDMENT 7/02/97:
- If a patient elects to receive indinavir, ORTHO/NOVUM 1/35 is an acceptable means of
birth control.
Patients must have:
- HIV infection.
- Disseminated MAC disease.
- Life expectancy of at least 8 weeks.
- Consent of parent or guardian if under 18 years of age.
NOTE:
- This protocol is approved for prisoner participation.
Prior Medication:
Allowed:
PER AMENDMENT 10/10/96:
- Therapy for acute infectious processes, other than MAC, prior to study entry.
Exclusion Criteria
Co-existing Condition:
Patients with the following symptoms or conditions are excluded:
- Active mycobacterial infection other than MAC that requires treatment, with the
exception of isoniazid used solely for TB prophylaxis.
Concurrent Medication:
Excluded:
- Other antimycobacterial drugs (with the exception of isoniazid for TB prophylaxis).
- Other investigational drugs unless approved by protocol chair.
PER AMENDMENT 7/2/97:
- For patients who elect to receive indinavir or ritonavir:
- Terfenadine, astemizole, cisapride, triazolam, or midazolam.
- For patients who elect to receive ritonavir:
- alprazolam, amiodarone, bepridil, bupropion, cisapride, clorazepate, clozapine,
diazepam, dihydroergotamine, ergotamine, estazolam, encainide, flecainide, flurazepam,
meperidine, pimozide, piroxicam, propafenone, propoxyphene, quinidine or zolpidem.
- For patients who elect to receive indinavir:
- oral contraceptives other than ORTHO/NOVUM as a sole form of birth control.
- For patients randomized to a rifabutin-containing arm:
- oral contraceptives or Norplant as a sole form of birth control.
Patients with the following prior condition are excluded:
- History of severe hypersensitivity to erythromycin, clarithromycin, azithromycin,
ethambutol, rifampin, or rifabutin (including Type 1 hypersensitivity reaction,
Stevens-Johnson syndrome, hepatitis, optic neuritis, or exfoliative dermatitis).
Prior Medication:
Excluded:
- Empiric or presumptive antimycobacterial therapy prior to study entry if > 14 days,
within 90 days prior to entry.
NOTE:
- Patients unwilling to discontinue presumptive therapy or empiric therapy may be
enrolled with the permission of the protocol chairs, however, if they are without a
MAC positive blood culture at baseline, they will have study medications discontinued
(AS PER AMENDMENT 7/2/97).
PER AMENDMENT 10/10/96:
- Treatment with clarithromycin or ethambutol within 4 days of initiation of study
medications.
- Treatment with rifabutin or rifampin within 7 days of initiation of study
medications.
Locations and Contacts
Univ of Alabama at Birmingham, Birmingham, Alabama 35294, United States
Univ of California / San Diego Treatment Ctr, San Diego, California 921036325, United States
San Francisco Gen Hosp, San Francisco, California 941102859, United States
UCLA CARE Ctr, Los Angeles, California 90095, United States
Univ of Southern California / LA County USC Med Ctr, Los Angeles, California 900331079, United States
Harbor UCLA Med Ctr, Torrance, California 90502, United States
Olive View Med Ctr, Sylmar, California 91342, United States
USC Univ Hosp & Ambulatory Hlth Care Ctr / USC Med Ctr, Los Angeles, California 900334508, United States
Univ of Colorado Health Sciences Ctr, Denver, Colorado 80262, United States
Kaiser Permanente Franklin Med Ctr, Denver, Colorado 80262, United States
Rose Med Ctr, Denver, Colorado 80262, United States
Med Ctr Clinic, Pensacola, Florida 325241151, United States
Regional Oncology Ctr, Daytona Beach, Florida 32015, United States
St Petersburg Med Clinics, St. Petersburg, Florida 33705, United States
Miami Veterans Administration Med Ctr, Miami, Florida 33125, United States
Emory Univ, Atlanta, Georgia 30308, United States
Queens Med Ctr, Honolulu, Hawaii 96816, United States
Univ of Hawaii, Honolulu, Hawaii 96816, United States
Northwestern Univ Med School, Chicago, Illinois 60611, United States
Rush Presbyterian - Saint Luke's Med Ctr, Chicago, Illinois 60612, United States
Cook County Hosp, Chicago, Illinois 60612, United States
Louis A Weiss Memorial Hosp, Chicago, Illinois 60640, United States
Indiana Univ Hosp, Indianapolis, Indiana 462025250, United States
Methodist Hosp of Indiana / Life Care Clinic, Indianapolis, Indiana 46202, United States
Division of Inf Diseases/ Indiana Univ Hosp, Indianapolis, Indiana 46202, United States
Wishard Hosp / Indiana Univ Hosp, Indianapolis, Indiana 46202, United States
Johns Hopkins Hosp, Baltimore, Maryland 21287, United States
Beth Israel Deaconess Med Ctr, Boston, Massachusetts 02215, United States
Boston Med Ctr, Boston, Massachusetts 02118, United States
Univ of Minnesota, Minneapolis, Minnesota 55455, United States
St Paul Ramsey Med Ctr, St. Paul, Minnesota 55101, United States
Hennepin County Med Clinic, Minneapolis, Minnesota 55415, United States
St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis, Missouri 63112, United States
Univ of Rochester Medical Center, Rochester, New York 14642, United States
Bellevue Hosp / New York Univ Med Ctr, New York, New York 10016, United States
Jack Weiler Hosp / Bronx Municipal Hosp, Bronx, New York 10465, United States
Bronx Municipal Hosp Ctr/Jacobi Med Ctr, Bronx, New York 10461, United States
SUNY / Erie County Med Ctr at Buffalo, Buffalo, New York 14215, United States
Beth Israel Med Ctr, New York, New York 10003, United States
Columbia Presbyterian Med Ctr, New York, New York 100323784, United States
Montefiore Adolescent AIDS Prog / Bronx Municipal Hosp, Bronx, New York 10461, United States
Univ of North Carolina, Chapel Hill, North Carolina 275997215, United States
Univ of Cincinnati, Cincinnati, Ohio 452670405, United States
Ohio State Univ Hosp Clinic, Columbus, Ohio 432101228, United States
Univ of Kentucky Lexington, Cincinnati, Ohio 45267, United States
Univ of Pennsylvania at Philadelphia, Philadelphia, Pennsylvania 19104, United States
Julio Arroyo, West Columbia, South Carolina 29169, United States
Vanderbilt Univ Med Ctr, Nashville, Tennessee 37203, United States
Univ of Washington, Seattle, Washington 981224304, United States
Additional Information
Click here for more information about Rifabutin Click here for more information about Clarithromycin Click here for more information about Indinavir sulfate Click here for more information about Ritonavir
Related publications: Flexner C, Noe D, Benson C, Currier J, Andrade A, Shaver A. Adherence patterns in patients with symptomatic Mycobacterium avium complex (MAC) infection taking a twice-daily clarithromycin regimen. ACTG 223 Study Team. Int Conf AIDS. 1998;12:585 (abstract no 32324) Benson CA, Williams PL, Currier JS, Holland F, Mahon LF, MacGregor RR, Inderlied CB, Flexner C, Neidig J, Chaisson R, Notario GF, Hafner R; AIDS Clinical Trials Group 223 Protocol Team. A prospective, randomized trial examining the efficacy and safety of clarithromycin in combination with ethambutol, rifabutin, or both for the treatment of disseminated Mycobacterium avium complex disease in persons with acquired immunodeficiency syndrome. Clin Infect Dis. 2003 Nov 1;37(9):1234-43. Epub 2003 Oct 03.
Last updated: June 23, 2005
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