A Phase II Safety and Efficacy Study of Clarithromycin in the Treatment of Disseminated M. Avium Complex (MAC) Infections in Patients With AIDS

This study has been completed.
Sponsor:
Collaborator:
Abbott
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000644
First received: November 2, 1999
Last updated: February 24, 2011
Last verified: February 2011
  Purpose

This study is designed to evaluate the efficacy and safety of clarithromycin given orally at 1 of 3 doses to treat disseminated Mycobacterium avium complex infections (MAC) in patients with AIDS.

Mycobacterium avium complex (MAC) is thought to be the most common disseminated bacterial opportunistic infection in AIDS, with clinical prevalence estimates ranging from 15 to 50 percent of all AIDS patients. Clarithromycin, a new macrolide antimicrobial agent, has demonstrated activity against MAC both in the laboratory and in animals. Clinical experience treating AIDS patients with clarithromycin for disseminated MAC is limited. However, early studies have indicated few adverse effects and some improvement in clinical symptoms scores and Karnofsky performance scores over placebo treated patients.


Condition Intervention Phase
Mycobacterium Avium-intracellulare Infection
HIV Infections
Drug: Clarithromycin
Phase 2

Study Type: Interventional
Study Design: Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Phase II Safety and Efficacy Study of Clarithromycin in the Treatment of Disseminated M. Avium Complex (MAC) Infections in Patients With AIDS

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 100
Primary Completion Date: November 1997 (Final data collection date for primary outcome measure)
Detailed Description:

Mycobacterium avium complex (MAC) is thought to be the most common disseminated bacterial opportunistic infection in AIDS, with clinical prevalence estimates ranging from 15 to 50 percent of all AIDS patients. Clarithromycin, a new macrolide antimicrobial agent, has demonstrated activity against MAC both in the laboratory and in animals. Clinical experience treating AIDS patients with clarithromycin for disseminated MAC is limited. However, early studies have indicated few adverse effects and some improvement in clinical symptoms scores and Karnofsky performance scores over placebo treated patients.

Treatment is randomly assigned so that twice as many patients receive clarithromycin at the lower dose as at an intermediate dose for 12 weeks. Once data becomes available to support dosing patients with clarithromycin at the highest dose, then treatment will be randomly assigned so that twice as many patients receive clarithromycin at the highest dose as at the intermediate dose. Sixteen patients per group (48 patients in all) will be enrolled. Patients exhibiting clinical improvement or clinical cure while on this trial will be allowed to continue on therapy for an additional 6 months. Patients will have clinical evaluations (including the Karnofsky Performance Scale), laboratory evaluations (hematology and chemistry), and blood cultures for MAC performed monthly.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Didanosine (ddI).
  • Dideoxycytidine (ddC).
  • Zidovudine (AZT).
  • Acetaminophen.
  • Acyclovir.
  • Fluconazole.
  • Erythropoietin (EPO).
  • Systemic Pneumocystis carinii pneumonia (PCP) prophylaxis (aerosolized or oral pentamidine, trimethoprim / sulfamethoxazole, or dapsone).
  • Maintenance ganciclovir therapy (permitted only if dose and clinical and laboratory parameters have been stable for at least 4 weeks prior to study entry).
  • Maintenance treatment for other opportunistic infections if the dose and clinical and laboratory parameters have been stable for 4 weeks prior to study entry.

Patients must have:

  • Positive results for HIV by ELISA confirmed by another method.
  • Positive blood culture for Mycobacterium avium complex within 2 months of study entry and clinical symptoms of MAC infection.
  • Discontinued all mycobacterial drugs (approved and investigational) for at least 4 weeks prior to the start of drug therapy (with the exception of isoniazid prophylaxis which should be discontinued at Study Day minus 14 to Study Day minus 7
  • Given written informed consent to participate in the trial.
  • Met the listed laboratory parameters in the pre-treatment visit.

Prior Medication:

Allowed:

  • Didanosine (ddI).
  • Deoxycytidine (ddC).
  • Zidovudine (AZT).
  • Acetaminophen.
  • Acyclovir.
  • Fluconazole.
  • Erythropoietin (EPO).
  • Systemic Pneumocystis carinii pneumonia (PCP) prophylaxis (aerosolized or oral pentamidine, dapsone, trimethoprim / sulfamethoxazole).
  • Maintenance ganciclovir therapy (permitted only if dose and clinical and laboratory parameters have been stable for at least 4 weeks prior to study entry).

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

  • Active opportunistic infections. Maintenance treatment for other opportunistic infections will be permitted if the dose and clinical and laboratory parameters have been stable for 4 weeks prior to study entry.

Concurrent Medication:

Excluded:

  • Aminoglycosides.
  • Ansamycin (rifabutin).
  • Quinolones.
  • Other macrolides.
  • Clofazimine.
  • Cytotoxic chemotherapy.
  • Rifampin.
  • Ethambutol.
  • Immunomodulators (except alpha interferon).
  • Investigational drugs (except ddI, ddC, and erythropoietin).

Patients with the following are excluded:

  • History of allergy to macrolide antimicrobials.
  • Currently on active therapy with any anti-mycobacterial drugs listed in Exclusion Prior Medications.
  • Currently on active therapy with carbamazepine or theophylline, unless the investigator agrees to carefully monitor blood levels.
  • Inability to comply with the protocol or judged to be near imminent death by the investigator.
  • Active opportunistic infections.
  • Requiring any of the excluded concomitant medications.

Prior Medication:

Excluded for at least 4 weeks prior to study entry:

  • All anti-mycobacterial drugs (approved and investigational) with the exception of isoniazid prophylaxis, which should be discontinued at Study Day minus 14 to minus 7.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000644

Locations
United States, California
Univ of Southern California / LA County USC Med Ctr
Los Angeles, California, United States, 900331079
United States, Illinois
Rush Presbyterian - Saint Luke's Med Ctr
Chicago, Illinois, United States, 60612
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Abbott
Investigators
Study Chair: Chaisson R
  More Information

Additional Information:
Publications:
Wu AW, Lichter SL, Richardson W, Urbanski PA, Benson C, Sattler FR, Chaisson R. Quality of life in patients receiving clarithromycin for Mycobacterium avium complex infection and AIDS. Int Conf AIDS. 1992 Jul 19-24;8(2):B178 (abstract no PoB 3550)
Chaisson RE, Benson CA, Dube M, Hafner R, Dellerson M, Lichter S, Smith T, Sattler FR. Clarithromycin for disseminated Mycobacterium avium-complex in AIDS patients. Int Conf AIDS. 1992 Jul 19-24;8(1):We54 (abstract no WeB 1052)

ClinicalTrials.gov Identifier: NCT00000644     History of Changes
Other Study ID Numbers: ACTG 157
Study First Received: November 2, 1999
Last Updated: February 24, 2011
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
AIDS-Related Opportunistic Infections
Mycobacterium avium-intracellulare Infection
Acquired Immunodeficiency Syndrome
Clarithromycin

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Mycobacterium Infections
Mycobacterium avium-intracellulare Infection
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Mycobacterium Infections, Nontuberculous
Clarithromycin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 14, 2014