SCH 39304 as Therapy for Acute Cryptococcal Meningitis in HIV-Infected Patients Followed by Maintenance Therapy

NCT ID: NCT00000677

Last Updated: 2005-06-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Brief Summary

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To assess the safety and effectiveness of SCH 39304 as primary treatment of acute cryptococcal meningitis in HIV-infected patients. Safety and effectiveness of maintenance therapy following successful treatment of acute disease are also evaluated.

Cryptococcal meningitis is a significant cause of illness and death in HIV-infected patients. Intravenous amphotericin B is effective for acute disease but relapse occurs in the majority of patients. Maintenance therapy is recommended but must be balanced against the multiple toxicities of the drugs used and the problems associated with the weekly administration of intravenous therapy. Treatments that are equally or more effective and less toxic than traditional methods are needed, especially oral therapy. SCH 39304 is an orally active antifungal drug that in animal studies is active against a wide range of systemic fungal infections including infections due to Cryptococcus. Features of SCH 39304 suggest that it might be of value in the treatment of cryptococcal meningitis.

Detailed Description

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Cryptococcal meningitis is a significant cause of illness and death in HIV-infected patients. Intravenous amphotericin B is effective for acute disease but relapse occurs in the majority of patients. Maintenance therapy is recommended but must be balanced against the multiple toxicities of the drugs used and the problems associated with the weekly administration of intravenous therapy. Treatments that are equally or more effective and less toxic than traditional methods are needed, especially oral therapy. SCH 39304 is an orally active antifungal drug that in animal studies is active against a wide range of systemic fungal infections including infections due to Cryptococcus. Features of SCH 39304 suggest that it might be of value in the treatment of cryptococcal meningitis.

HIV-infected patients with a diagnosis of acute cryptococcal meningitis, previously untreated or relapsed following a successfully treated acute episode, are enrolled in the study. SCH 39304 is administered orally once daily for 3 days followed by a lower dose once daily for 12 weeks. Patients who respond to primary therapy are randomized to receive SCH 39304 maintenance therapy at a higher dose once weekly or at the lower dose once daily for up to 12 months under this protocol.

Conditions

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Meningitis, Cryptococcal HIV Infections

Study Design

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Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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SCH 39304

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Concurrent Medication:

Allowed:

* Currently approved antiviral therapy.
* Maintenance therapy for cytomegalovirus retinitis or toxoplasmosis.
* Rifampin.
* Isoniazid.
* Dilantin or barbiturates if investigator agrees to rigorously monitor anticonvulsant drug levels.
* Coumarin-type anticoagulants if investigator agrees to rigorously monitor prothrombin time.
* Prophylactic treatment for Pneumocystis carinii pneumonia (PCP).

Concurrent Treatment:

Allowed:

* Local radiotherapy for mucocutaneous Kaposi's sarcoma.

Prior Medication:

Allowed:

* Amphotericin B, up to 1 mg/kg, during the previous 7 days.

Patients must be HIV positive by 2 methodologies and have either primary cryptococcal meningitis with no prior anti-cryptococcal therapy or relapsed disease after prior therapy.

* Prior therapy for cryptococcal meningitis is limited to approved drugs.
* Written informed consent either from patient or patient's parent or legal guardian is required.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

* History of hypersensitivity to imidazole or azole compounds.
* Central nervous system disease.
* Acute opportunistic infection.
* Underlying conditions that in the opinion of the investigator could preclude assessment of response.

Concurrent Medication:

Excluded:

* Systemic antifungal drugs other than study drug.
* Any investigational drug other than treatment IND drugs.
* Oral hypoglycemic agents.
* Oral contraceptives.
* Cytotoxic chemotherapy.

Patients with the following are excluded:

* Unable to take oral medications.
* Concurrent central nervous system disease which in opinion of investigator would interfere with assessment of response.
* Concurrent acute opportunistic infection requiring therapy (patients who develop an acute opportunistic infection after initiation of study medication may remain on study medication).

Prior Medication:

Excluded within 7 days of study entry:

* Amphotericin B, \> 1 mg/kg.
Minimum Eligible Age

13 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Schering-Plough

INDUSTRY

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Principal Investigators

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WG Powderly

Role: STUDY_CHAIR

Locations

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Birmingham Veterans Administration Med Ctr

Birmingham, Alabama, United States

Site Status

Dr Robert Larsen

Los Angeles, California, United States

Site Status

Univ of California / San Diego Treatment Ctr

San Diego, California, United States

Site Status

San Francisco AIDS Clinic / San Francisco Gen Hosp

San Francisco, California, United States

Site Status

George Washington Univ Med Ctr

Washington D.C., District of Columbia, United States

Site Status

Emory Univ School of Medicine

Atlanta, Georgia, United States

Site Status

Med College of Georgia

Augusta, Georgia, United States

Site Status

Rush Presbyterian - Saint Luke's Med Ctr

Chicago, Illinois, United States

Site Status

Indiana Univ Hosp

Indianapolis, Indiana, United States

Site Status

Tulane Univ School of Medicine

New Orleans, Louisiana, United States

Site Status

Univ Hosp

Boston, Massachusetts, United States

Site Status

St Louis Regional Hosp / St Louis Regional Med Ctr

St Louis, Missouri, United States

Site Status

Erie County Med Ctr

Buffalo, New York, United States

Site Status

Beth Israel Med Ctr

New York, New York, United States

Site Status

Mount Sinai Med Ctr

New York, New York, United States

Site Status

Univ of Rochester Medical Center

Rochester, New York, United States

Site Status

Bronx Veterans Administration / Mount Sinai Hosp

The Bronx, New York, United States

Site Status

Univ of North Carolina

Chapel Hill, North Carolina, United States

Site Status

Duke Univ Med Ctr

Durham, North Carolina, United States

Site Status

Holmes Hosp / Univ of Cincinnati Med Ctr

Cincinnati, Ohio, United States

Site Status

Univ Hosp of Cleveland / Case Western Reserve Univ

Cleveland, Ohio, United States

Site Status

Ohio State Univ Med Ctr

Columbus, Ohio, United States

Site Status

Buckley Braffman Stern Med Associates

Philadelphia, Pennsylvania, United States

Site Status

Julio Arroyo

West Columbia, South Carolina, United States

Site Status

Houston Veterans Administration Med Ctr

Houston, Texas, United States

Site Status

Univ TX Health Science Ctr

Houston, Texas, United States

Site Status

Audie L Murphy Veterans Administration Hosp

San Antonio, Texas, United States

Site Status

Richmond AIDS Consortium

Richmond, Virginia, United States

Site Status

Countries

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United States

References

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Lee BL, Padula AM, Tauber MG, Chambers HF, Sande MA. Oral SCH 39304 as primary, salvage, and maintenance therapy for cryptococcal meningitis in AIDS. J Acquir Immune Defic Syndr (1988). 1992;5(6):600-4.

Reference Type BACKGROUND
PMID: 1588494 (View on PubMed)

Other Identifiers

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C89-258

Identifier Type: -

Identifier Source: secondary_id

ACTG 125

Identifier Type: -

Identifier Source: org_study_id