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

NCT00000641 | Completed Phase 2

• 2 other identifiers: ACTG 13511110
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 16

Brief 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).

Conditions

Mycobacterium Avium-intracellulare Infection; HIV Infections

Keywords

Rifampin; Mycobacterium avium-intracellulare Infection; Drug Evaluation; Drug Therapy, Combination; Ethambutol; Clofazimine; Acquired Immunodeficiency Syndrome; Amikacin; Azithromycin; Ciprofloxacin

Interventions

Ciprofloxacin hydrochloride DRUG

Ethambutol hydrochloride DRUG

Amikacin sulfate DRUG

Azithromycin DRUG

Rifampin DRUG

Clofazimine DRUG

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (16)

Harbor-UCLA Med. Ctr. CRS

Torrance, California, 90502, United States

Location

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, 46202, United States

Location

St. Louis ConnectCare, Infectious Diseases Clinic

St Louis, Missouri, United States

Location

Washington U CRS

St Louis, Missouri, United States

Location

NJ Med. School CRS

Newark, New Jersey, 07103, United States

Location

NY Univ. HIV/AIDS CRS

New York, New York, 10016, United States

Location

Beth Israel Med. Ctr. (Mt. Sinai)

New York, New York, United States

Location

NYU Med. Ctr., Dept. of Medicine

New York, New York, United States

Location

Univ. of Rochester ACTG CRS

Rochester, New York, 14642, United States

Location

Unc Aids Crs

Chapel Hill, North Carolina, 27599, United States

Location

Duke Univ. Med. Ctr. Adult CRS

Durham, North Carolina, 27710, United States

Location

Regional Center for Infectious Disease, Wendover Medical Center CRS

Greensboro, North Carolina, United States

Location

Univ. of Cincinnati CRS

Cincinnati, Ohio, 45267, United States

Location

Case CRS

Cleveland, Ohio, 44106, United States

Location

Pitt CRS

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Washington AIDS CRS

Seattle, Washington, 98122, United States

Location

Related Publications (3)

• 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

  BACKGROUND

• 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. doi: 10.1093/infdis/163.6.1326.

  PMID: 2037799 BACKGROUND

• 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. doi: 10.1097/00002030-199818000-00013.

  PMID: 9875582 BACKGROUND

MeSH Terms

Conditions

Mycobacterium avium-intracellulare Infection; HIV Infections; Acquired Immunodeficiency Syndrome

Interventions

Ciprofloxacin; Ethambutol; Amikacin; Azithromycin; Rifampin; Clofazimine

Condition Hierarchy (Ancestors)

Mycobacterium Infections, Nontuberculous; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Ethylenediamines; Diamines; Polyamines; Amines; Organic Chemicals; Kanamycin; Aminoglycosides; Glycosides; Carbohydrates; Erythromycin; Macrolides; Polyketides; Lactones; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Phenazines; Heterocyclic Compounds, 3-Ring

Study Officials

• DM Parenti

  STUDY CHAIR

• J Ellner

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: December 1, 1994
• Last Updated: November 3, 2021

Record last verified: 2021-10

Locations

US (16)