Back to resultsA Phase II/III Trial of Rifampin, Ciprofloxacin, Clofazimine, Ethambutol, and Amikacin in the Treatment of Disseminated Mycobacterium Avium Infection in HIV-Infected Individuals.
Primary Purpose
Mycobacterium Avium-intracellulare Infection, HIV Infections
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ciprofloxacin hydrochloride
Ethambutol hydrochloride
Amikacin sulfate
Azithromycin
Rifampin
Clofazimine
Sponsored by
About this trial
This is an interventional treatment trial for Mycobacterium Avium-intracellulare Infection focused on measuring Rifampin, Mycobacterium avium-intracellulare Infection, Drug Evaluation, Drug Therapy, Combination, Ethambutol, Clofazimine, Acquired Immunodeficiency Syndrome, Amikacin, Azithromycin, Ciprofloxacin
Eligibility 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.
Sites / Locations
- Harbor-UCLA Med. Ctr. CRS
- Indiana Univ. School of Medicine, Infectious Disease Research Clinic
- St. Louis ConnectCare, Infectious Diseases Clinic
- Washington U CRS
- NJ Med. School CRS
- NY Univ. HIV/AIDS CRS
- Beth Israel Med. Ctr. (Mt. Sinai)
- NYU Med. Ctr., Dept. of Medicine
- Univ. of Rochester ACTG CRS
- Unc Aids Crs
- Duke Univ. Med. Ctr. Adult CRS
- Regional Center for Infectious Disease, Wendover Medical Center CRS
- Univ. of Cincinnati CRS
- Case CRS
- Pitt CRS
- University of Washington AIDS CRS
Outcomes
Primary Outcome Measures
Secondary Outcome Measures
Full Information
NCT ID
NCT00000641
First Posted
November 2, 1999
Last Updated
October 26, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
1. Study Identification
Unique Protocol Identification Number
NCT00000641
Brief 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.
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 Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
December 1994 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
4. Oversight
5. Study Description
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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Masking
None (Open Label)
Enrollment
90 (false)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Ciprofloxacin hydrochloride
Intervention Type
Drug
Intervention Name(s)
Ethambutol hydrochloride
Intervention Type
Drug
Intervention Name(s)
Amikacin sulfate
Intervention Type
Drug
Intervention Name(s)
Azithromycin
Intervention Type
Drug
Intervention Name(s)
Rifampin
Intervention Type
Drug
Intervention Name(s)
Clofazimine
10. Eligibility
Sex
All
Minimum Age & Unit of Time
13 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
DM Parenti
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
J Ellner
Official's Role
Study Chair
Facility Information:
Facility Name
Harbor-UCLA Med. Ctr. CRS
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
St. Louis ConnectCare, Infectious Diseases Clinic
City
Saint Louis
State/Province
Missouri
Country
United States
Facility Name
Washington U CRS
City
Saint Louis
State/Province
Missouri
Country
United States
Facility Name
NJ Med. School CRS
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07103
Country
United States
Facility Name
NY Univ. HIV/AIDS CRS
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Beth Israel Med. Ctr. (Mt. Sinai)
City
New York
State/Province
New York
Country
United States
Facility Name
NYU Med. Ctr., Dept. of Medicine
City
New York
State/Province
New York
Country
United States
Facility Name
Univ. of Rochester ACTG CRS
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Unc Aids Crs
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Duke Univ. Med. Ctr. Adult CRS
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Regional Center for Infectious Disease, Wendover Medical Center CRS
City
Greensboro
State/Province
North Carolina
Country
United States
Facility Name
Univ. of Cincinnati CRS
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Case CRS
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Pitt CRS
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
University of Washington AIDS CRS
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States
12. IPD Sharing Statement
Citations:
Citation
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
Results Reference
background
PubMed Identifier
2037799
Citation
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.
Results Reference
background
PubMed Identifier
9875582
Citation
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.
Results Reference
background
Learn more about this trial
A Phase II/III Trial of Rifampin, Ciprofloxacin, Clofazimine, Ethambutol, and Amikacin in the Treatment of Disseminated Mycobacterium Avium Infection in HIV-Infected Individuals.
We'll reach out to this number within 24 hrs