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A Comparison of Three Drug Combinations Containing Clarithromycin in the Treatment of Mycobacterium Avium Complex (MAC) Disease in Patients With AIDS

This study has been completed.
Study NCT00001058.   Last updated on July 31, 2008.   Information provided by National Institute of Allergy and Infectious Diseases (NIAID)

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Descriptive Information Fields
Brief Title  A Comparison of Three Drug Combinations Containing Clarithromycin in the Treatment of Mycobacterium Avium Complex (MAC) Disease in Patients With AIDS
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
Brief 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.

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.

Study Phase Phase II
Study Type  Interventional
Study Design  Treatment, Safety Study
Primary Outcome Measure 
Secondary Outcome Measure 
Condition  Mycobacterium Avium-Intracellulare Infection
HIV Infections
Intervention  Drug: Indinavir sulfate
Drug: Ritonavir
Drug: Ethambutol hydrochloride
Drug: Clarithromycin
Drug: Rifabutin
MEDLINE PMIDs 14557969
Links Click here for more information about Rifabutin This link exits the ClinicalTrials.gov site
Click here for more information about Clarithromycin This link exits the ClinicalTrials.gov site
Click here for more information about Indinavir sulfate This link exits the ClinicalTrials.gov site
Click here for more information about Ritonavir This link exits the ClinicalTrials.gov site
Recruitment Information Fields
Recruitment Status  Completed
Enrollment  246
Start Date 
Completion Date
Eligibility 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.
Gender Both
Ages 13 Years and older
Accepts Healthy Volunteers No
Contacts ††
Location Countries  United States
Administrative Information Fields
NCT ID  NCT00001058
Organization ID ACTG 223
Secondary IDs ††
Study Sponsor  National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators ††
Investigators 
Study Chair:     Benson CA        
Study Chair:     Chaisson RE        
Study Chair:     Currier JS        
Information Provided By National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date June 1999
First Received Date  November 2, 1999
Last Updated Date July 31, 2008

 †    Required WHO trial registration data element.
††   WHO trial registration data element that is required only if it exists.




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