A Pilot Study of Oral Clindamycin and Pyrimethamine for the Treatment of Toxoplasmic Encephalitis in Patients With AIDS

HIV Infections Clinical Trial

Official title:

A Pilot Study of Oral Clindamycin and Pyrimethamine for the Treatment of Toxoplasmic Encephalitis in Patients With AIDS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000674
• Other study ID #: ACTG 077P
• Secondary ID: 11052ACTG 077 PI
• Status: Completed
• Phase: N/A
• First received: November 2, 1999
• Last updated: May 17, 2012
• Est. completion date: August 1992

Study information

• Verified date: May 2012
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

To collect information on the effectiveness and toxicity of clindamycin plus pyrimethamine and leucovorin calcium for the treatment of acute toxoplasmic encephalitis in adult patients with AIDS. Toxoplasmic encephalitis (encephalitis caused by Toxoplasma gondii) is the most frequent cause of focal central nervous system infection in patients with AIDS. If untreated, the encephalitis is fatal. At present, it is standard practice to give a combination of pyrimethamine and sulfadiazine to treat toxoplasmic encephalitis. The high frequency of sulfonamide-induced toxicity in AIDS patients often makes completion of a full course of therapy difficult. There is some information that high doses of parenteral (such as by injection) clindamycin used with pyrimethamine may be as effective as pyrimethamine plus sulfadiazine in the management of the acute phase of toxoplasmic encephalitis in patients with AIDS. Administration of parenteral clindamycin for prolonged periods of time, however, is costly, requires hospitalization, and is inconvenient for the patient. There is some indication that treatment of AIDS patients with acute toxoplasmic encephalitis with oral clindamycin may be effective. Leucovorin calcium is useful in preventing pyrimethamine-associated bone marrow toxicity.

Description:

Toxoplasmic encephalitis (encephalitis caused by Toxoplasma gondii) is the most frequent cause of focal central nervous system infection in patients with AIDS. If untreated, the encephalitis is fatal. At present, it is standard practice to give a combination of pyrimethamine and sulfadiazine to treat toxoplasmic encephalitis. The high frequency of sulfonamide-induced toxicity in AIDS patients often makes completion of a full course of therapy difficult. There is some information that high doses of parenteral (such as by injection) clindamycin used with pyrimethamine may be as effective as pyrimethamine plus sulfadiazine in the management of the acute phase of toxoplasmic encephalitis in patients with AIDS. Administration of parenteral clindamycin for prolonged periods of time, however, is costly, requires hospitalization, and is inconvenient for the patient. There is some indication that treatment of AIDS patients with acute toxoplasmic encephalitis with oral clindamycin may be effective. Leucovorin calcium is useful in preventing pyrimethamine-associated bone marrow toxicity.

Amended: Projected accrual increased to 50 patients. Original design: Patients receive study medications for a total of 6 weeks unless there are intervening events that require the discontinuation of study therapy. Patients are initially treated in the hospital (minimum of 7 days). Patients who are considered responders at day 7 may complete therapy on an outpatient basis. Nonresponders at day 7 may also be managed on an outpatient basis when it is medically appropriate.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: August 1992
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years and older

Eligibility

Inclusion Criteria

Concurrent Medication:

Allowed:

• Erythropoietin.

• Aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia (PCP).

• Immunoglobulin therapy.

• Alpha interferon.

• Patients entering study on isoniazid (INH) may continue INH therapy.

• Use of corticosteroids is discouraged. If corticosteroids are needed for the management of intracranial hypertension or cranial mass effect, use of dexamethasone is encouraged (4 g orally 4 times daily for 3 days and thereafter tapered over the next 10 to 14 days).

Patients are admitted into the study if they have:

• Laboratory evidence of HIV infection or if they have an undetermined HIV infection status if they belong to a high-risk group for HIV infection.

• Either a definite or presumptive diagnosis of toxoplasmic encephalitis. Patient or appropriate family member, or legal designee must be able to understand and sign a written informed consent.

Allowed:

• HIV encephalopathy.

AMENDED:

• Allows patients who have relapsed. Patients with a previous diagnosis of toxoplasmic encephalitis based on histopathology or documented neuroradiological response to pyrimethamine and sulfonamides or pyrimethamine and clindamycin and who have relapsed toxoplasmic encephalitis. Relapse must be documented by definite progression of lesions or appearance of new lesions compatible with toxoplasmic encephalitis.

Prior Medication:

Allowed if liver enzymes stable for 6 weeks prior to study entry:

• Rifampin.

• Isoniazid.

Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

• Infections of the central nervous system.

• Malabsorption syndrome (3 or more loose stools a day for at least 4 weeks associated with an unintentional weight loss of at least 10 percent of body weight).

• History of sensitivity to the study medication.

• Malignancies requiring the use of cytotoxic chemotherapy.

• Coma.

• Diffuse central white matter lesions.

• Negative serology for Toxoplasma as performed at the Palo Alto Medical Foundation (unless biopsy is positive).

• Lymphoma of the central nervous system.

• Cerebral Kaposi's sarcoma.

• Hemorrhagic diathesis or active bleeding disorder.

Concurrent Medication:

Excluded:

• Erythromycin or other macrolides.

• Sulfonamides.

• Immunomodulators.

• Cytotoxic chemotherapy.

• Amphotericin.

• Dapsone.

• Rifamycins.

• Ganciclovir.

• Allopurinol.

• Antifolates.

• Azidothymidine and other antiretrovirals and investigational agents not specifically allowed.

• Folate supplements.

• Isoniazid (INH) therapy may not be started while on therapy.

Concurrent Treatment:

Excluded:

• Lymphocyte replacement.

Patients with the following are excluded:

• Negative HIV antibodies by a federally licensed ELISA (as determined at or after study entry), unless there is documentation of a previously positive HIV culture or p24 antigen.

• Coma.

• Diffuse central white matter lesions.

• Negative serology for Toxoplasma as performed at the Palo Alto Medical Foundation (unless biopsy is positive).

• Lymphoma of the central nervous system.

• Cerebral Kaposi's sarcoma.

• Hemorrhagic diathesis or active bleeding disorder.

• Unable to take oral medications reliably.

• Any medical or social condition which, in the opinion of the investigator, would adversely affect either participation and/or compliance in this study.

Prior Medication:

Excluded:

• Treatment for toxoplasmic encephalitis.

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Encephalitis
• HIV Infections
• Toxoplasmosis
• Toxoplasmosis, Cerebral

Intervention

Drug:
• Pyrimethamine

• Leucovorin calcium

• Clindamycin

Locations

Country	Name	City	State
United States	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland
United States	SUNY - Buffalo, Erie County Medical Ctr.	Buffalo	New York
United States	Unc Aids Crs	Chapel Hill	North Carolina
United States	Duke Univ. Med. Ctr. Adult CRS	Durham	North Carolina
United States	USC CRS	Los Angeles	California
United States	Univ. of Miami AIDS CRS	Miami	Florida
United States	Cornell University A2201	New York	New York
United States	Memorial Sloan-Kettering Cancer Ctr.	New York	New York
United States	NY Univ. HIV/AIDS CRS	New York	New York
United States	Stanford CRS	Palo Alto	California
United States	Pitt CRS	Pittsburgh	Pennsylvania
United States	Ucsd, Avrc Crs	San Diego	California
United States	Washington U CRS	St. Louis	Missouri

Sponsors (3)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Glaxo Wellcome, Upjohn

Country where clinical trial is conducted

United States, 

References & Publications (1)

Luft BJ, Hafner R, Korzun AH, Leport C, Antoniskis D, Bosler EM, Bourland DD 3rd, Uttamchandani R, Fuhrer J, Jacobson J, et al. Toxoplasmic encephalitis in patients with the acquired immunodeficiency syndrome. Members of the ACTG 077p/ANRS 009 Study Team. N Engl J Med. 1993 Sep 30;329(14):995-1000. — View Citation