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

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.

History of severe allergic reactions to study medication Currently pregnant or breastfeeding Recent participation in another clinical trial within the last 30 days Presence of uncontrolled medical conditions that could affect safety