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)
Information obtained from ClinicalTrials.gov on June 20, 2008
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
Status: Completed
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
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).
Clinical Details
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: Treatment, Open Label
Detailed description:
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.
Eligibility
Minimum age: 13 Years.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
San Juan City Hosp, San Juan 009367344, Puerto Rico
Huntington Memorial Hosp / Children's Hosp of Los Angeles, Pasadena, California 91105, United States
Harbor UCLA Med Ctr, Torrance, California 90502, United States
George Washington Univ Med Ctr, Washington, District of Columbia 20037, United States
Indiana Univ Hosp, Indianapolis, Indiana 462025250, United States
Harvard (Massachusetts Gen Hosp), Boston, Massachusetts 02114, United States
Beth Israel Deaconess Med Ctr, Boston, Massachusetts 02215, United States
Beth Israel Deaconess - West Campus, Boston, Massachusetts 02215, United States
Boston Med Ctr, Boston, Massachusetts 02118, United States
Baystate Med Ctr of Springfield, Springfield, Massachusetts 01199, United States
Univ of Massachusetts Med Ctr, Worcester, Massachusetts 01655, United States
Children's Hosp of Michigan, Detroit, Michigan 48201, United States
St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis, Missouri 63112, United States
Univ of Medicine & Dentistry of New Jersey / Univ Hosp, Newark, New Jersey 071032714, United States
Montefiore Drug Treatment Ctr / Bronx Municipal Hosp, Bronx, New York 10461, United States
Montefiore Family Health Ctr / Bronx Municipal Hosp, Bronx, New York 10461, United States
Samaritan Village Inc / Bronx Municipal Hosp, Bronx, New York 10461, United States
Nassau County Med Ctr, East Meadow, New York 11554, United States
SUNY / State Univ of New York, Syracuse, New York 13210, United States
SUNY - Stony Brook, Stony Brook, New York 117948153, United States
Univ of Rochester Medical Center, Rochester, New York 14642, United States
Bellevue Hosp / New York Univ Med Ctr, New York, New York 10016, United States
Mem Sloan - Kettering Cancer Ctr, New York, New York 10021, United States
Jack Weiler Hosp / Bronx Municipal Hosp, Bronx, New York 10465, United States
Saint Luke's - Roosevelt Hosp Ctr, New York, New York 10025, United States
Bronx Municipal Hosp Ctr/Jacobi Med Ctr, Bronx, New York 10461, United States
Montefiore Med Ctr / Bronx Municipal Hosp, Bronx, New York 10467, United States
North Central Bronx Hosp / Bronx Municipal Hosp, Bronx, New York 10467, United States
Univ of North Carolina, Chapel Hill, North Carolina 275997215, United States
Duke Univ Med Ctr, Durham, North Carolina 27710, United States
Case Western Reserve Univ, Cleveland, Ohio 44106, United States
Univ of Cincinnati, Cincinnati, Ohio 452670405, United States
Univ of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States
Hemophilia Ctr of Western PA / Univ of Pittsburgh, Pittsburgh, Pennsylvania 15219, United States
Univ of Pittsburgh Med School / Hershey Med Ctr, Hershey, Pennsylvania 170330850, United States
Julio Arroyo, West Columbia, South Carolina 29169, United States
Univ Texas Health Science Ctr / Univ Texas Med School, Houston, Texas 77030, United States
Univ of Washington, Seattle, Washington 981224304, United States
Additional Information
Click here for more information about Azithromycin Click here for more information about Rifampin
Related publications: 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: June 23, 2005
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