A Phase II/III Trial of Rifampin, Ciprofloxacin, Clofazimine, Ethambutol, and Amikacin in the Treatment of Disseminated Mycobacterium Avium Infection in HIV-Infected Individuals.
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Mycobacterium Avium-intracellulare Infection; HIV Infections
Intervention: Ciprofloxacin hydrochloride (Drug); Ethambutol hydrochloride (Drug); Amikacin sulfate (Drug); Azithromycin (Drug); Rifampin (Drug); Clofazimine (Drug)
Phase: Phase 2
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Official(s) and/or principal investigator(s):
DM Parenti, Study Chair
J Ellner, Study Chair
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).
Official title: A Phase II/III Trial of Rifampin, Ciprofloxacin, Clofazimine, Ethambutol, and Amikacin in the Treatment of Disseminated Mycobacterium Avium Infection in HIV-Infected Individuals.
Study design: Masking: Open Label, Primary Purpose: Treatment
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
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.
Minimum age: 13 Years.
Maximum age: N/A.
- 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
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
- Ability and willingness to participate in all components of the study and receive all
- Single drug prophylaxis for Mycobacterium avium or M. tuberculosis within the
previous 4 weeks.
Patients with the following symptoms or conditions are excluded:
- Known or suspected allergy to any of the study medications. Severe hearing loss.
- Severe hearing loss. Hypersensitivity to macrolides. Intolerance to ethambutol and
- 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.
- 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.
Locations and Contacts
Harbor-UCLA Med. Ctr. CRS, Torrance, California 90502, United States
Indiana Univ. School of Medicine, Infectious Disease Research Clinic, Indianapolis, Indiana 46202, United States
St. Louis ConnectCare, Infectious Diseases Clinic, St Louis, Missouri, United States
Washington U CRS, St. Louis, Missouri, United States
NJ Med. School CRS, Newark, New Jersey 07103, United States
Beth Israel Med. Ctr. (Mt. Sinai), New York, New York, United States
NY Univ. HIV/AIDS CRS, New York, New York 10016, United States
NYU Med. Ctr., Dept. of Medicine, New York, New York, United States
Univ. of Rochester ACTG CRS, Rochester, New York 14642, United States
Unc Aids Crs, Chapel Hill, North Carolina 27599, United States
Duke Univ. Med. Ctr. Adult CRS, Durham, North Carolina 27710, United States
Regional Center for Infectious Disease, Wendover Medical Center CRS, Greensboro, North Carolina, United States
Univ. of Cincinnati CRS, Cincinnati, Ohio 45267, United States
Case CRS, Cleveland, Ohio 44106, United States
Pitt CRS, Pittsburgh, Pennsylvania 15213, United States
University of Washington AIDS CRS, Seattle, Washington 98122, United States
Click here for more information about Azithromycin
Click here for more information about Rifampin
Parent D, Ellner J, Hafner R, Williams M, Jacobs P, Hojczyk P. A phase II/III trial of Rifampin (RIF) Ciprofloxach (CIPRO), Clofazimine (CLOF), Ethambutol (ETH), +/- Amikacin (AK) in the treatment (RX) of Disseminated Mycobacterium avium (MA) infection in HIV-infected individuals (PTS). Natl Conf Hum Retroviruses Relat Infect (2nd). 1995 Jan 29-Feb 2:56
Ellner JJ, Goldberger MJ, Parenti DM. Mycobacterium avium infection and AIDS: a therapeutic dilemma in rapid evolution. J Infect Dis. 1991 Jun;163(6):1326-35. Review.
Parenti DM, Williams PL, Hafner R, Jacobs MR, Hojczyk P, Hooton TM, Barber TW, Simpson G, van der Horst C, Currier J, Powderly WG, Limjoco M, Ellner JJ. A phase II/III trial of antimicrobial therapy with or without amikacin in the treatment of disseminated Mycobacterium avium infection in HIV-infected individuals. AIDS Clinical Trials Group Protocol 135 Study Team. AIDS. 1998 Dec 24;12(18):2439-46.
Last updated: March 29, 2012