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Mycobacterium Avium-intracellulare InfectionPhase 2NCT00001058

A Comparison of Three Drug Combinations Containing Clarithromycin in the Treatment of Mycobacterium Avium Complex (MAC) Disease in Patients With AIDS

A Phase 2 study testing Indinavir sulfate, Ritonavir and Ethambutol hydrochloride in people with Mycobacterium Avium-intracellulare Infection and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 34 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

To compare the efficacy and safety of clarithromycin combined with rifabutin, ethambutol, or both in the treatment of disseminated Mycobacterium avium Complex (MAC) disease in persons with AIDS, including individuals who have or have not received prior MAC prophylaxis. Read more about this study

Who is it for?
Ages 13 years and older
What is being tested?
Indinavir sulfate, Ritonavir and Ethambutol hydrochloride
How many people
246 participants
Where
34 sitesin 2 countries
Study dates
Start not givento Jan 1999
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 13 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Concurrent Medication:
  • Allowed:
  • Antiretroviral therapy.
  • Maintenance or prophylactic therapy for other opportunistic infections (with the exception of specifically excluded drugs).
  • Carbamazepine or theophylline.
  • Isoniazid for TB prophylaxis.
Show all 22Show fewer
  • PER AMENDMENT 10/10/96:
  • Therapy for acute infectious processes, other than MAC, provided that the patient is stable on the therapy.
  • Fluconazole therapy for maintenance or suppression of fungal infections, providing the patient has been on a stable dose for at least 4 weeks.
  • PER AMENDMENT 7/02/97:
  • If a patient elects to receive indinavir, ORTHO/NOVUM 1/35 is an acceptable means of birth control.
  • Patients must have:
  • HIV infection.
  • Disseminated MAC disease.
  • Life expectancy of at least 8 weeks.
  • Consent of parent or guardian if under 18 years of age.
  • NOTE:
  • This protocol is approved for prisoner participation.
  • Prior Medication:
  • Allowed:
  • PER AMENDMENT 10/10/96:
  • Therapy for acute infectious processes, other than MAC, prior to study entry.

Who cannot join

  • Co-existing Condition:
  • Patients with the following symptoms or conditions are excluded:
  • Active mycobacterial infection other than MAC that requires treatment, with the exception of isoniazid used solely for TB prophylaxis.
  • Concurrent Medication:
  • Excluded:
  • Other antimycobacterial drugs (with the exception of isoniazid for TB prophylaxis).
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  • Other investigational drugs unless approved by protocol chair.
  • PER AMENDMENT 7/2/97:
  • For patients who elect to receive indinavir or ritonavir:
  • Terfenadine, astemizole, cisapride, triazolam, or midazolam.
  • For patients who elect to receive ritonavir:
  • alprazolam, amiodarone, bepridil, bupropion, cisapride, clorazepate, clozapine, diazepam, dihydroergotamine, ergotamine, estazolam, encainide, flecainide, flurazepam, meperidine, pimozide, piroxicam, propafenone, propoxyphene, quinidine or zolpidem.
  • For patients who elect to receive indinavir:
  • oral contraceptives other than ORTHO/NOVUM as a sole form of birth control.
  • For patients randomized to a rifabutin-containing arm:
  • oral contraceptives or Norplant as a sole form of birth control.
  • Patients with the following prior condition are excluded:
  • History of severe hypersensitivity to erythromycin, clarithromycin, azithromycin, ethambutol, rifampin, or rifabutin (including Type 1 hypersensitivity reaction, Stevens-Johnson syndrome, hepatitis, optic neuritis, or exfoliative dermatitis).
  • Prior Medication:
  • Excluded:
  • Empiric or presumptive antimycobacterial therapy prior to study entry if > 14 days, within 90 days prior to entry.
  • NOTE:
  • Patients unwilling to discontinue presumptive therapy or empiric therapy may be enrolled with the permission of the protocol chairs, however, if they are without a MAC positive blood culture at baseline, they will have study medications discontinued (AS PER AMENDMENT 7/2/97).
  • PER AMENDMENT 10/10/96:
  • Treatment with clarithromycin or ethambutol within 4 days of initiation of study medications.
  • Treatment with rifabutin or rifampin within 7 days of initiation of study medications.

Trial locations and contacts

34 sites in 2 countries.

34 sites in 2 countries

United States33 sites

  • The Ponce de Leon Ctr. CRS

    Atlanta, Georgia, 30308

  • University of Colorado Hospital CRS

    Aurora, Colorado, 80045

  • Johns Hopkins Adult AIDS CRS

    Baltimore, Maryland, 21287

  • Alabama Therapeutics CRS

    Birmingham, Alabama, 35294

  • Bmc Actg Crs

    Boston, Massachusetts, 02118

  • Beth Israel Deaconess - East Campus A0102 CRS

    Boston, Massachusetts, 02215

  • SUNY - Buffalo, Erie County Medical Ctr.

    Buffalo, New York, 14260

  • Unc Aids Crs

    Chapel Hill, North Carolina, 27514

  • Northwestern University CRS

    Chicago, Illinois, 60611

  • Cook County Hosp. CORE Ctr.

    Chicago, Illinois, 60612

  • Rush Univ. Med. Ctr. ACTG CRS

    Chicago, Illinois, 60612

  • Weiss Memorial Hosp.

    Chicago, Illinois, 60640

  • Univ. of Cincinnati CRS

    Cincinnati, Ohio, 45267

  • The Ohio State Univ. AIDS CRS

    Columbus, Ohio, 43210

  • Queens Med. Ctr.

    Honolulu, Hawaii, 96813

  • Univ. of Hawaii at Manoa, Leahi Hosp.

    Honolulu, Hawaii, 96816

  • Indiana Univ. School of Medicine, Infectious Disease Research Clinic

    Indianapolis, Indiana, 46202

  • Indiana Univ. School of Medicine, Wishard Memorial

    Indianapolis, Indiana, 46202

  • Methodist Hosp. of Indiana

    Indianapolis, Indiana, 46202

  • USC CRS

    Los Angeles, California, 90033

  • UCLA CARE Center CRS

    Los Angeles, California, 90035

  • Hennepin County Med. Ctr., Div. of Infectious Diseases

    Minneapolis, Minnesota, 55415

  • University of Minnesota, ACTU

    Minneapolis, Minnesota, 55455

  • Beth Israel Med. Ctr. (Mt. Sinai)

    New York, New York, 10003

  • NY Univ. HIV/AIDS CRS

    New York, New York, 10016

  • Hosp. of the Univ. of Pennsylvania CRS

    Philadelphia, Pennsylvania, 19104

  • Univ. of Rochester ACTG CRS

    Rochester, New York, 14642

  • Ucsd, Avrc Crs

    San Diego, California, 92103

  • Ucsf Aids Crs

    San Francisco, California, 94110

  • University of Washington AIDS CRS

    Seattle, Washington, 98104

  • Washington U CRS

    St Louis, Missouri, 63110

  • St. Louis ConnectCare, Infectious Diseases Clinic

    St Louis, Missouri, 63112

  • Harbor-UCLA Med. Ctr. CRS

    Torrance, California, 90502

Other trials in United States

Tanzania1 site

  • Mbeya Med. Research Program, Mbeya Referral Hosp. CRS

    Mbeya

Other trials in Tanzania

About this study

Official title: A Phase II/III Prospective, Multicenter, Randomized, Controlled Trial Comparing the Safety and Efficacy of Three Clarithromycin-Containing Combination Drug Regimens for the Treatment of Disseminated Mycobacterium Avium Complex (MAC) Disease in Persons With AIDS

To compare the efficacy and safety of clarithromycin combined with rifabutin, ethambutol, or both in the treatment of disseminated Mycobacterium avium Complex (MAC) disease in persons with AIDS, including individuals who have or have not received prior MAC prophylaxis.

It is believed that effective therapy for MAC disease in patients with AIDS requires combinations of two or more antimycobacterial agents in order to overcome drug resistance and the unfavorable influence of the profound immunosuppression associated with AIDS. Data suggest that clarithromycin may have substantial activity in two- or three-drug combination regimens with clofazimine, rifamycin derivatives, ethambutol, or the 4-quinolones.

Read the detailed description

It is believed that effective therapy for MAC disease in patients with AIDS requires combinations of two or more antimycobacterial agents in order to overcome drug resistance and the unfavorable influence of the profound immunosuppression associated with AIDS. Data suggest that clarithromycin may have substantial activity in two- or three-drug combination regimens with clofazimine, rifamycin derivatives, ethambutol, or the 4-quinolones.

Patients are randomized to one of three treatment arms containing clarithromycin in combination with ethambutol, rifabutin, or both. Clarithromycin alone is taken on days 1 through 3 to determine tolerance and rifabutin and/or ethambutol is added on day 3. AS PER AMENDMENT 7/2/97: Patients may elect to add ritonavir or indinavir to their treatment regimen. Treatment continues daily for 48 weeks. In the absence of a dose-limiting toxicity, those patients who are determined to be complete or partial responders continue on the regimen to which they were originally assigned. Patients who have failed or relapsed on originally assigned MAC therapy, must have their therapy amended to receive clarithromycin and at least two other drugs not included in their originally assigned regimen. Patients are followed twice in the first week, then every 2 weeks for the first 2 months, then monthly for the next 4 months, and then every 2 months thereafter until the end of 12 months. PER AMENDMENT 10/10/96: NOTE: Any patient who develops a toxicity to rifabutin or ethambutol after week 12 or thereafter will be offered the option of being registered to a salvage regimen of 2 new drugs not previously received, plus clarithromycin to continue for the study duration.

Being tested
Indinavir sulfate, Ritonavir, Ethambutol hydrochloride, Clarithromycin, Rifabutin
Keywords
Rifabutin, Mycobacterium avium-intracellulare Infection, Drug Therapy, Combination, Ethambutol, Clofazimine, Acquired Immunodeficiency Syndrome, Ciprofloxacin, Clarithromycin
Medical subject headings
Mycobacterium avium-intracellulare Infection, HIV Infections, Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2001 (estimated)
  2. Study completionJan 1999

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Enrolment
246 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00001058
Sponsor's protocol ID
ACTG 223
Other IDs
11200
Status last verified
Oct 2021
First submitted
2 Nov 1999
Last updated
1 Nov 2021
Results posted
No

Publications

  • Flexner C, Noe D, Benson C, Currier J, Andrade A, Shaver A. Adherence patterns in patients with symptomatic Mycobacterium avium complex (MAC) infection taking a twice-daily clarithromycin regimen. ACTG 223 Study Team. Int Conf AIDS. 1998;12:585 (abstract no 32324)

  • Benson CA, Williams PL, Currier JS, Holland F, Mahon LF, MacGregor RR, Inderlied CB, Flexner C, Neidig J, Chaisson R, Notario GF, Hafner R; AIDS Clinical Trials Group 223 Protocol Team. A prospective, randomized trial examining the efficacy and safety of clarithromycin in combination with ethambutol, rifabutin, or both for the treatment of disseminated Mycobacterium avium complex disease in persons with acquired immunodeficiency syndrome. Clin Infect Dis. 2003 Nov 1;37(9):1234-43. doi: 10.1086/378807. Epub 2003 Oct 3.

    PubMed 14557969

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Indinavir sulfate, Ritonavir and Ethambutol hydrochloride in people with Mycobacterium Avium-intracellulare Infection and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 34 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 34 sites in United States, Tanzania. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00001058, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2021.

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