A Pilot Study of Oral Clindamycin and Pyrimethamine for the Treatment of Toxoplasmic Encephalitis in Patients With AIDS
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Toxoplasmosis, Cerebral; HIV Infections
Intervention: Pyrimethamine (Drug); Leucovorin calcium (Drug); Clindamycin (Drug)
Phase: N/A
Status: Completed
Sponsored by: Upjohn Official(s) and/or principal investigator(s):
Remington JS, Study Chair
Luft B, Study Chair
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.
Clinical Details
Official title: A Pilot Study of Oral Clindamycin and Pyrimethamine for the Treatment of Toxoplasmic Encephalitis in Patients With AIDS
Study design: Treatment, Open Label
Detailed 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.
Eligibility
Minimum age: 13 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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.
Locations and Contacts
Univ of California / San Diego Treatment Ctr, San Diego, California 921036325, United States
Stanford at Kaiser / Kaiser Permanente Med Ctr, San Francisco, California 94115, United States
Stanford Univ Med Ctr, Stanford, California 943055107, United States
Palo Alto Veterans Adm Med Ctr / Stanford Univ, Palo Alto, California 94304, United States
Univ of Southern California / LA County USC Med Ctr, Los Angeles, California 900331079, United States
Univ of Miami School of Medicine, Miami, Florida 331361013, United States
Northwestern Univ Med School, Chicago, Illinois 60611, United States
Charity Hosp / Tulane Univ Med School, New Orleans, Louisiana 70112, United States
Louisiana State Univ Med Ctr / Tulane Med School, New Orleans, Louisiana 70112, United States
Tulane Univ School of Medicine, New Orleans, Louisiana 70112, United States
Johns Hopkins Hosp, Baltimore, Maryland 21287, United States
Baystate Med Ctr of Springfield, Springfield, Massachusetts 01199, United States
Univ of Massachusetts Med Ctr, Worcester, Massachusetts 01655, United States
SUNY - Stony Brook, Stony Brook, New York 117948153, United States
Mem Sloan - Kettering Cancer Ctr, New York, New York 10021, United States
Bellevue Hosp / New York Univ Med Ctr, New York, New York 10016, United States
Mount Sinai Med Ctr, New York, New York 10029, United States
Jack Weiler Hosp / Bronx Municipal Hosp, Bronx, New York 10465, United States
Cornell Univ Med Ctr, New York, New York 10021, United States
Saint Luke's - Roosevelt Hosp Ctr, New York, New York 10025, United States
Bronx Municipal Hosp Ctr/Jacobi Med Ctr, Bronx, New York 10461, United States
Montefiore Med Ctr / Bronx Municipal Hosp, Bronx, New York 10467, United States
Bronx Veterans Administration / Mount Sinai Hosp, Bronx, New York 10468, United States
SUNY / Erie County Med Ctr at Buffalo, Buffalo, New York 14215, United States
Beth Israel Med Ctr, New York, New York 10003, United States
City Hosp Ctr at Elmhurst / Mount Sinai Hosp, Elmhurst, New York 11373, United States
North Central Bronx Hosp / Bronx Municipal Hosp, Bronx, New York 10467, United States
Univ of North Carolina, Chapel Hill, North Carolina 275997215, United States
Duke Univ Med Ctr, Durham, North Carolina 27710, United States
Ohio State Univ Hosp Clinic, Columbus, Ohio 432101228, United States
Univ of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States
Presbyterian Univ Hosp / Univ of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States
Julio Arroyo, West Columbia, South Carolina 29169, United States
Additional Information
Related publications: 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.
Last updated: June 23, 2005
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