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.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001058
First received: November 2, 1999
Last updated: April 2, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Mycobacterium Avium-intracellulare Infection
HIV Infections
Drug: Indinavir sulfate
Drug: Ritonavir
Drug: Ethambutol hydrochloride
Drug: Clarithromycin
Drug: Rifabutin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 246
Study Completion Date: January 1999
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

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00001058

  Show 34 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Benson CA
Study Chair: Chaisson RE
Study Chair: Currier JS
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001058     History of Changes
Other Study ID Numbers: ACTG 223, 11200
Study First Received: November 2, 1999
Last Updated: April 2, 2012
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Rifabutin
Mycobacterium avium-intracellulare Infection
Drug Therapy, Combination
Ethambutol
Clofazimine
Acquired Immunodeficiency Syndrome
Ciprofloxacin
Clarithromycin

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Mycobacterium Infections
Mycobacterium avium-intracellulare Infection
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Mycobacterium Infections, Atypical
Ethambutol
Rifabutin
Clarithromycin
Indinavir
Ritonavir
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014