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

This study has been completed.
Sponsor:
Collaborators:
Upjohn
Glaxo Wellcome
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000674
First received: November 2, 1999
Last updated: May 17, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention
Toxoplasmosis, Cerebral
HIV Infections
Drug: Pyrimethamine
Drug: Leucovorin calcium
Drug: Clindamycin

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Oral Clindamycin and Pyrimethamine for the Treatment of Toxoplasmic Encephalitis 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: 30
Study Completion Date: August 1992
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

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT00000674

Locations
United States, California
USC CRS
Los Angeles, California, United States, 90033
Stanford CRS
Palo Alto, California, United States, 94304
Ucsd, Avrc Crs
San Diego, California, United States, 92103
United States, Florida
Univ. of Miami AIDS CRS
Miami, Florida, United States, 33136
United States, Maryland
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, United States, 21287
United States, Missouri
Washington U CRS
St. Louis, Missouri, United States
United States, New York
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, United States, 14215
Memorial Sloan-Kettering Cancer Ctr.
New York, New York, United States, 10021
NY Univ. HIV/AIDS CRS
New York, New York, United States, 10016
Cornell University A2201
New York, New York, United States, 10021
United States, North Carolina
Unc Aids Crs
Chapel Hill, North Carolina, United States, 27599
Duke Univ. Med. Ctr. Adult CRS
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Pitt CRS
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Upjohn
Glaxo Wellcome
Investigators
Study Chair: Remington JS
Study Chair: Luft B
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000674     History of Changes
Other Study ID Numbers: ACTG 077P, 11052, ACTG 077 PILOT
Study First Received: November 2, 1999
Last Updated: May 17, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Toxoplasmosis
AIDS-Related Opportunistic Infections
Pyrimethamine
Leucovorin
Drug Evaluation
Drug Therapy, Combination
Encephalitis
Acquired Immunodeficiency Syndrome
Clindamycin

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Encephalitis
Toxoplasmosis
Toxoplasmosis, Cerebral
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
Central Nervous System Viral Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Central Nervous System Infections
Coccidiosis
Protozoan Infections
Parasitic Diseases
Brain Abscess
Abscess
Suppuration
Infection
Central Nervous System Protozoal Infections
Central Nervous System Parasitic Infections
Clindamycin
Clindamycin-2-phosphate

ClinicalTrials.gov processed this record on July 24, 2014