Toxoplasmosis, CerebralNCT00000674
A Pilot Study of Oral Clindamycin and Pyrimethamine for the Treatment of Toxoplasmic Encephalitis in Patients With AIDS
A study testing Pyrimethamine, Leucovorin calcium and Clindamycin in people with Toxoplasmosis, Cerebral and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 13 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 13 years and older
- Conditions the study is for
- Toxoplasmosis, Cerebral, HIV Infections
- What is being tested?
- Pyrimethamine, Leucovorin calcium and Clindamycin
- How many people
- 30 participants
- Where
- 13 sitesUnited States
- Study dates
- Start not givento Aug 1992
- Phase
- Interventional
- 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:
- Erythropoietin.
- Aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia (PCP).
- Immunoglobulin therapy.
- Alpha interferon.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, 21287
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, 14215
Unc Aids Crs
Chapel Hill, North Carolina, 27599
Duke Univ. Med. Ctr. Adult CRS
Durham, North Carolina, 27710
USC CRS
Los Angeles, California, 90033
Univ. of Miami AIDS CRS
Miami, Florida, 33136
NY Univ. HIV/AIDS CRS
New York, New York, 10016
Cornell University A2201
New York, New York, 10021
Memorial Sloan-Kettering Cancer Ctr.
New York, New York, 10021
Stanford CRS
Palo Alto, California, 94304
Pitt CRS
Pittsburgh, Pennsylvania, 15213
Ucsd, Avrc Crs
San Diego, California, 92103
Washington U CRS
St Louis, Missouri
About this study
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.
Read the 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.
- Conditions
- Toxoplasmosis, Cerebral, HIV Infections
- Being tested
- Pyrimethamine, Leucovorin calcium, Clindamycin
- Keywords
- Toxoplasmosis, AIDS-Related Opportunistic Infections, Pyrimethamine, Leucovorin, Drug Evaluation, Drug Therapy, Combination, Encephalitis, Acquired Immunodeficiency Syndrome, Clindamycin
- Medical subject headings
- Toxoplasmosis, Cerebral, HIV Infections, Toxoplasmosis, AIDS-Related Opportunistic Infections, Encephalitis, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PyrimethamineDrug
ClindamycinDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
- Study completionAug 1992
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Toxoplasmosis, CerebralStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Treatment
- Masking
- None (open label)
- Enrolment
- 30 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Upjohn, Glaxo Wellcome
- Responsible party
- Sponsor
- Investigators
- Remington JS, Study chairLuft B, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000674
- Sponsor's protocol ID
- ACTG 077P
- Other IDs
- 11052, ACTG 077 PILOT
- Status last verified
- May 2012
- First submitted
- 2 Nov 1999
- Last updated
- 18 May 2012
- Results posted
- No
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. doi: 10.1056/NEJM199309303291403.
PubMed 8366923
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Oral Clindamycin and Pyrimethamine for the Treatment of Toxoplasmic Encephalitis in Patients With AIDS
- ClinicalTrials.gov ID
- NCT00000674
- Acronym / sponsor ID
- ACTG 077P
- Conditions
- Toxoplasmosis, Cerebral, HIV Infections
- Keywords
- Toxoplasmosis, AIDS-Related Opportunistic Infections, Pyrimethamine, Leucovorin, Drug Evaluation, Drug Therapy, Combination, Encephalitis, Acquired Immunodeficiency Syndrome
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Upjohn, Glaxo Wellcome
- Study completion
- Aug 1992 (actual)
- First posted
- 31 Aug 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- 13 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (19 listed)
- Erythropoietin.
- Aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia (PCP).
- Immunoglobulin therapy.
- Alpha interferon.
- Patients entering study on isoniazid (INH) may continue INH therapy.
Key exclusion criteria (43 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pyrimethamine | Drug | – |
| Leucovorin calcium | Drug | – |
| Clindamycin | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2012.
- Background: PubMed 8366923Luft 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. doi: 10.1056/NEJM199309303291403.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Remington JS study chair
Luft B study chair
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pyrimethamine, Leucovorin calcium and Clindamycin in people with Toxoplasmosis, Cerebral and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 13 sites in United States.
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 19 inclusion and 43 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 18 May 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. 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.
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 NCT00000674, which also lists 1 linked publication.
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 18 May 2012.