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The Safety and Effectiveness of Clarithromycin and Rifabutin Used Alone or in Combination to Prevent Mycobacterium Avium Complex (MAC) or Disseminated MAC Disease in HIV-Infected Patients

Primary Purpose

Mycobacterium Avium-intracellulare Infection, HIV Infections

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Clarithromycin
Rifabutin
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mycobacterium Avium-intracellulare Infection focused on measuring Rifabutin, Mycobacterium avium-intracellulare Infection, Acquired Immunodeficiency Syndrome, Clarithromycin

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria Concurrent Medication: Recommended: PCP prophylaxis. Allowed: GM-CSF or G-CSF. Erythropoietin. Therapies (including antiretrovirals) available through expanded access or treatment IND programs. Other non-experimental therapies available by prescription. Antihistamines other than those specifically excluded. Patients must have: Evidence or diagnosis of HIV infection or a history of an AIDS-defining condition by CDC criteria. CD4 count <= 100 cells/mm3 within 90 days prior to study entry. Two baseline blood sample cultures negative for MAC within 30 days of study entry. No suspected disseminated MAC disease, in the opinion of the clinician. NOTE: Patients with elevated GGT and/or triglycerides are allowed. NOTE: Patients may co-enroll on ACTG 081/981/181, ACTG 175, ACTG 204, ACTG 193, ACTG 241, or other acceptable protocols. Exclusion Criteria Co-existing Condition: Patients with the following symptoms or conditions are excluded: Known or suspected tuberculous infection or other non-tuberculous mycobacterial infection requiring chemotherapy or chemoprophylaxis (with the exception of isoniazid prophylaxis alone). NOTE: Patients may enroll who successfully completed tuberculosis (TB) treatment and have been off anti-TB drugs for more than 6 months with no symptoms of mycobacterial infection. Active TB. Known hypersensitivity to study drugs. Malabsorption as defined by persistent diarrhea with more than 8 stools per day for > 6 weeks. Concurrent Medication: Excluded: Frequent (more than once per month), repeated, or continuous treatment courses of quinolones, erythromycin, spiramycin, azithromycin, clarithromycin, or clindamycin. Concomitant terfenadine or astemizole. Prior Medication: Excluded: Prophylaxis with azithromycin, clarithromycin, or rifabutin for more than 4 months.

Sites / Locations

  • Alabama Therapeutics CRS
  • UCLA CARE Center CRS
  • Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.
  • Ucsf Aids Crs
  • Howard University Hosp., Div. of Infectious Diseases, ACTU
  • Univ. of Miami AIDS CRS
  • Univ. of Hawaii at Manoa, Leahi Hosp.
  • Chicago Children's CRS
  • Northwestern University CRS
  • Cook County Hosp. CORE Ctr.
  • Rush Univ. Med. Ctr. ACTG CRS
  • Indiana Univ. School of Medicine, Infectious Disease Research Clinic
  • Methodist Hosp. of Indiana
  • Univ. of Iowa Healthcare, Div. of Infectious Diseases
  • Johns Hopkins Adult AIDS CRS
  • Massachusetts General Hospital ACTG CRS
  • Bmc Actg Crs
  • Beth Israel Deaconess - East Campus A0102 CRS
  • Beth Israel Deaconess Med. Ctr., ACTG CRS
  • Hennepin County Med. Ctr., Div. of Infectious Diseases
  • University of Minnesota, ACTU
  • St. Louis ConnectCare, Infectious Diseases Clinic
  • Washington U CRS
  • Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.
  • Bronx-Lebanon Hosp. IMPAACT CRS
  • SUNY - Buffalo, Erie County Medical Ctr.
  • NY Univ. HIV/AIDS CRS
  • Memorial Sloan-Kettering Cancer Ctr.
  • Beth Israel Med. Ctr. (Mt. Sinai)
  • Cornell University A2201
  • Univ. of Rochester ACTG CRS
  • Unc Aids Crs
  • Carolinas HealthCare System, Carolinas Med. Ctr.
  • Regional Center for Infectious Disease, Wendover Medical Center CRS
  • Univ. of Cincinnati CRS
  • Case CRS
  • MetroHealth CRS
  • The Ohio State Univ. AIDS CRS
  • Hosp. of the Univ. of Pennsylvania CRS
  • The Children's Hosp. of Philadelphia IMPAACT CRS
  • University of Washington AIDS CRS
  • Mbeya Med. Research Program, Mbeya Referral Hosp. CRS

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 28, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00001030
Brief Title
The Safety and Effectiveness of Clarithromycin and Rifabutin Used Alone or in Combination to Prevent Mycobacterium Avium Complex (MAC) or Disseminated MAC Disease in HIV-Infected Patients
Official Title
A Prospective, Randomized, Comparative Study of the Safety and Efficacy of Clarithromycin Versus Rifabutin Versus the Combination of Clarithromycin Plus Rifabutin for the Prevention of Mycobacterium Avium Complex (MAC) Bacteremia or Disseminated MAC Disease in HIV-Infected Patients With CD4 Lymphocyte Counts <= 100 Cells/mm3
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
June 1996 (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 efficacy and safety of clarithromycin alone versus rifabutin alone versus the two drugs in combination for the prevention or delay of Mycobacterium avium Complex (MAC) bacteremia or disseminated MAC disease. To compare other parameters such as survival, toxicity, and quality of life among the three treatment arms. To obtain information on the incidence and clinical grade of targeted gynecologic conditions. Persons with advanced stages of HIV are considered to be at particular risk for developing disseminated MAC disease. The development of an effective regimen for the prevention of disseminated MAC disease may be of substantial benefit in altering the morbidity and possibly the mortality associated with this disease and its treatment.
Detailed Description
Persons with advanced stages of HIV are considered to be at particular risk for developing disseminated MAC disease. The development of an effective regimen for the prevention of disseminated MAC disease may be of substantial benefit in altering the morbidity and possibly the mortality associated with this disease and its treatment. Patients are randomized to receive clarithromycin alone, rifabutin alone, or the two drugs in combination daily. Patients are evaluated every 4 weeks for the first 8 weeks and every 8 weeks thereafter for the duration of the study. Patients are followed for 24 months. Per amendment, a pharmacokinetic substudy will be conducted.

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
Rifabutin, Mycobacterium avium-intracellulare Infection, Acquired Immunodeficiency Syndrome, Clarithromycin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Enrollment
1100 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Clarithromycin
Intervention Type
Drug
Intervention Name(s)
Rifabutin

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Concurrent Medication: Recommended: PCP prophylaxis. Allowed: GM-CSF or G-CSF. Erythropoietin. Therapies (including antiretrovirals) available through expanded access or treatment IND programs. Other non-experimental therapies available by prescription. Antihistamines other than those specifically excluded. Patients must have: Evidence or diagnosis of HIV infection or a history of an AIDS-defining condition by CDC criteria. CD4 count <= 100 cells/mm3 within 90 days prior to study entry. Two baseline blood sample cultures negative for MAC within 30 days of study entry. No suspected disseminated MAC disease, in the opinion of the clinician. NOTE: Patients with elevated GGT and/or triglycerides are allowed. NOTE: Patients may co-enroll on ACTG 081/981/181, ACTG 175, ACTG 204, ACTG 193, ACTG 241, or other acceptable protocols. Exclusion Criteria Co-existing Condition: Patients with the following symptoms or conditions are excluded: Known or suspected tuberculous infection or other non-tuberculous mycobacterial infection requiring chemotherapy or chemoprophylaxis (with the exception of isoniazid prophylaxis alone). NOTE: Patients may enroll who successfully completed tuberculosis (TB) treatment and have been off anti-TB drugs for more than 6 months with no symptoms of mycobacterial infection. Active TB. Known hypersensitivity to study drugs. Malabsorption as defined by persistent diarrhea with more than 8 stools per day for > 6 weeks. Concurrent Medication: Excluded: Frequent (more than once per month), repeated, or continuous treatment courses of quinolones, erythromycin, spiramycin, azithromycin, clarithromycin, or clindamycin. Concomitant terfenadine or astemizole. Prior Medication: Excluded: Prophylaxis with azithromycin, clarithromycin, or rifabutin for more than 4 months.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Benson CA
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Cohn DL
Official's Role
Study Chair
Facility Information:
Facility Name
Alabama Therapeutics CRS
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
UCLA CARE Center CRS
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
Ucsf Aids Crs
City
San Francisco
State/Province
California
Country
United States
Facility Name
Howard University Hosp., Div. of Infectious Diseases, ACTU
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20059
Country
United States
Facility Name
Univ. of Miami AIDS CRS
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Univ. of Hawaii at Manoa, Leahi Hosp.
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96816
Country
United States
Facility Name
Chicago Children's CRS
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Northwestern University CRS
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Cook County Hosp. CORE Ctr.
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Rush Univ. Med. Ctr. ACTG CRS
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
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
Methodist Hosp. of Indiana
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Univ. of Iowa Healthcare, Div. of Infectious Diseases
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Johns Hopkins Adult AIDS CRS
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Massachusetts General Hospital ACTG CRS
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Bmc Actg Crs
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Beth Israel Deaconess - East Campus A0102 CRS
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Beth Israel Deaconess Med. Ctr., ACTG CRS
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Hennepin County Med. Ctr., Div. of Infectious Diseases
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55415
Country
United States
Facility Name
University of Minnesota, ACTU
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
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
Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Bronx-Lebanon Hosp. IMPAACT CRS
City
Bronx
State/Province
New York
ZIP/Postal Code
10457
Country
United States
Facility Name
SUNY - Buffalo, Erie County Medical Ctr.
City
Buffalo
State/Province
New York
ZIP/Postal Code
14215
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
Memorial Sloan-Kettering Cancer Ctr.
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Beth Israel Med. Ctr. (Mt. Sinai)
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Cornell University A2201
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
Carolinas HealthCare System, Carolinas Med. Ctr.
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
Regional Center for Infectious Disease, Wendover Medical Center CRS
City
Greensboro
State/Province
North Carolina
ZIP/Postal Code
27401
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
MetroHealth CRS
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44109
Country
United States
Facility Name
The Ohio State Univ. AIDS CRS
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Hosp. of the Univ. of Pennsylvania CRS
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
The Children's Hosp. of Philadelphia IMPAACT CRS
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Washington AIDS CRS
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States
Facility Name
Mbeya Med. Research Program, Mbeya Referral Hosp. CRS
City
Mbeya
Country
Tanzania

12. IPD Sharing Statement

Citations:
Citation
Currier JS, Williams P, Feinberg J, Becker S, Owens S, Benson CA. ACTG 815: a prospective study of bacterial infections in advanced HIV disease. Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:131 (abstract no 364)
Results Reference
background
PubMed Identifier
11364022
Citation
Mascolini M. FDA advisory committee deadlocks on delavirdine. Food and Drug Administration. AIDS Treat News. 1996 Dec 6;(No 260):3-5.
Results Reference
background
Citation
Watts DH, Spino C, Benson C, Yu B, Katzenstein D, Hammer S, Stratton P, Korvick J. A comparison of gynecologic findings in HIV-positive women with CD4 lymphocyte counts 200 to 500/cc and less than 100/cc. Int Conf AIDS. 1996 Jul 7-12;11(2):275 (abstract no ThB4137)
Results Reference
background
PubMed Identifier
11153670
Citation
Fichtenbaum CJ, Zackin R, Feinberg J, Benson C, Griffiths JK; AIDS Clinical Trials Group New Works Concept Sheet Team 064. Rifabutin but not clarithromycin prevents cryptosporidiosis in persons with advanced HIV infection. AIDS. 2000 Dec 22;14(18):2889-93. doi: 10.1097/00002030-200012220-00010.
Results Reference
background
PubMed Identifier
9358195
Citation
Cohn DL. Prevention strategies for Mycobacterium avium-intracellulare complex (MAC) infection. A review of recent studies in patients with AIDS. Drugs. 1997;54 Suppl 2:8-15; discussion 28-9. doi: 10.2165/00003495-199700542-00004.
Results Reference
background
PubMed Identifier
10225227
Citation
Watts DH, Spino C, Zaborski L, Katzenstein D, Hammer S, Benson C. Comparison of gynecologic history and laboratory results in HIV-positive women with CD4+ lymphocyte counts between 200 and 500 cells/microl and below 100 cells/microl. J Acquir Immune Defic Syndr Hum Retrovirol. 1999 Apr 15;20(5):455-62. doi: 10.1097/00042560-199904150-00007.
Results Reference
background
PubMed Identifier
9524822
Citation
Fichtenbaum CJ, Powderly WG. Refractory mucosal candidiasis in patients with human immunodeficiency virus infection. Clin Infect Dis. 1998 Mar;26(3):556-65. doi: 10.1086/514571.
Results Reference
background
PubMed Identifier
10762562
Citation
Benson CA, Williams PL, Cohn DL, Becker S, Hojczyk P, Nevin T, Korvick JA, Heifets L, Child CC, Lederman MM, Reichman RC, Powderly WG, Notario GF, Wynne BA, Hafner R. Clarithromycin or rifabutin alone or in combination for primary prophylaxis of Mycobacterium avium complex disease in patients with AIDS: A randomized, double-blind, placebo-controlled trial. The AIDS Clinical Trials Group 196/Terry Beirn Community Programs for Clinical Research on AIDS 009 Protocol Team. J Infect Dis. 2000 Apr;181(4):1289-97. doi: 10.1086/315380. Epub 2000 Apr 13.
Results Reference
background
PubMed Identifier
11340534
Citation
Currier JS, Williams P, Feinberg J, Becker S, Owens S, Fichtenbaum C, Benson C; Adult Clinical Trial Group. Impact of prophylaxis for Mycobacterium avium complex on bacterial infections in patients with advanced human immunodeficiency virus disease. Clin Infect Dis. 2001 Jun 1;32(11):1615-22. doi: 10.1086/320515. Epub 2001 Apr 30.
Results Reference
background

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The Safety and Effectiveness of Clarithromycin and Rifabutin Used Alone or in Combination to Prevent Mycobacterium Avium Complex (MAC) or Disseminated MAC Disease in HIV-Infected Patients

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