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

 Patients undergo an initial 2-week observation period (days 1 - 14) during which time
 baseline evaluations are performed and type and severity of symptoms are monitored. Eligible
 patients are randomized on day 15 to one of two treatment programs: (1) ciprofloxacin,
 clofazimine, ethambutol, and rifampin (all taken orally), or (2) the same four drugs plus
 amikacin. Only patients for whom blood cultures obtained on either day 1 or day 14/15 are
 positive by week 6 continue on study drugs. Patients receive combination therapy for 24
 weeks. Patients may have an indwelling central venous catheter in place for long-term
 administration of intravenous drug. PER 03/06/92 AMENDMENT: Newly enrolled patients who
 demonstrate a complete or partial clinical response at the end of study week 10 (8 weeks of
 drug therapy) discontinue their current regimen and begin maintenance therapy with
 azithromycin plus either ethambutol or clofazimine for an additional 24 weeks. Patients who
 do not demonstrate a response at study week 10 are discontinued from all study therapy.
 Patients enrolled on earlier versions of the protocol who have surpassed study week 16 (14
 weeks of drug therapy) continue treatment with their originally assigned regimen through
 study week 26; those who have not surpassed study week 16 are considered for inclusion in the
 maintenance phase of the study.
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.