A Phase II/III Trial of Rifampin, Ciprofloxacin, Clofazimine, Ethambutol, and Amikacin in the Treatment of Disseminated Mycobacterium Avium Infection in HIV-Infected Individuals.

• Status: Completed
• Trial end date: 1994-12-01
• Target enrollment: 0
• Participant gender: All

Summary

To compare the effectiveness and toxicity of two combination drug treatment programs for the treatment of disseminated Mycobacterium avium infection in HIV seropositive patients. [Per 03/06/92 amendment: to evaluate the efficacy of azithromycin when given in conjunction with either ethambutol or clofazimine as maintenance therapy.] Disseminated M. avium infection is the most common systemic bacterial infection complicating AIDS in the United States. The prognosis of patients with disseminated M. avium is extremely poor, particularly when it follows other opportunistic infections or is associated with anemia. Test tube studies and clinical data indicate that the best treatment program may include clofazimine, ethambutol, a rifamycin derivative, and ciprofloxacin. Test tube and animal studies indicate that amikacin is a bactericidal (bacteria destroying) drug that works better when used with ciprofloxacin. Its role in treatment programs is a key issue because of toxicity and because it must be administered parenterally (by injection or intravenously).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Amikacin; Azithromycin; Ciprofloxacin; Clofazimine; Ethambutol; Rifampin

Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

• Zidovudine (AZT) and didanosine (ddI). Dideoxycytidine (ddC), EPO, and other experimental therapies granted Treatment IND or Expanded Access status, with the exception of rifabutin.

• Concurrent therapies (acute and maintenance) for opportunistic infections not specifically prohibited.

Concurrent Treatment:

Allowed:

• Interferon-alfa.

Patients must have the following:

• HIV infections or diagnosis of AIDS as per CDC classification.

• Mycobacterium avium isolated from blood.

• Capability of signing an informed consent, or consent of guardian if < 18 years of age.

• Ability and willingness to participate in all components of the study and receive all study therapies.

Prior Medication:

Allowed:

• Interferon-alfa.

• Single drug prophylaxis for Mycobacterium avium or M. tuberculosis within the previous 4 weeks.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

Treatment Phase:

• Known or suspected allergy to any of the study medications. Severe hearing loss.

Maintenance Phase:

• Severe hearing loss. Hypersensitivity to macrolides. Intolerance to ethambutol and clofazimine.

Concurrent Medication:

Excluded:

• Acute therapy for other opportunistic infections at time of study entry.

• Nephrotoxic agents such as amphotericin B, intravenous vancomycin, or foscarnet during the first 4 weeks of study therapy without specific exemption from one of the protocol chairs. Antacids within 2 hours of ingestion of study drugs.

• Immunomodulators (except interferon-alfa) and other antimycobacterial drugs (including quinolones and aminoglycosides).

• All experimental therapies (except ddI, ddC, and other experimental agents granted "Treatment IND" or "expanded access" status) will be prohibited (specific exemptions must be obtained from one of the protocol chairs).

Patients with the following are excluded:

• Known or suspected allergy to any of the study medications. Cannot take drugs orally.

• Severe hearing loss, at the discretion of the investigator.

Prior Medication:

Excluded:

• Antimycobacterial drugs (including azithromycin, clarithromycin, rifamycins, quinolones, and aminoglycosides) or immunomodulators (except interferon-alfa) within 4 weeks prior to entry, except single-drug prophylaxis specifically allowed.

History of unreliable drug intake.

• Inability to cooperate in the testing procedures.