Toxoplasmosis, CerebralPhase 1NCT00000966
A Study of Azithromycin Plus Pyrimethamine in the Treatment of a Brain Infection in Patients With AIDS
A Phase 1 study testing Azithromycin, Pyrimethamine and Leucovorin calcium in people with Toxoplasmosis, Cerebral and HIV Infections, run by Pfizer at 11 sites in United States.
Trial summary
To evaluate the effectiveness and toxicity of oral azithromycin and pyrimethamine as acute therapy for toxoplasmic encephalitis in AIDS patients. To assess the toxicity and effectiveness of azithromycin alone as maintenance therapy. 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?
- Azithromycin, Pyrimethamine and Leucovorin calcium
- How many people
- 45 participants
- Where
- 11 sitesUnited States
- Study dates
- Start not givento not given
- Phase
- Phase 1
- 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:
- Aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia (PCP).
- Allowed during maintenance period (weeks 7 - 24):
- Zidovudine and other antiretrovirals available through treatment IND mechanisms, ganciclovir, and maintenance doses of amphotericin (other investigational therapies require permission from the study chair), steroids for the treatment of acute PCP.
- Isoniazid (INH) only for patients already on INH.
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- Patients must have the following:
- HIV infection or belong to high-risk group. Presumptive or definite diagnosis of toxoplasmic encephalitis.
- Each patient, or his/her appropriate family member, or legal designee must be able to understand and sign a written informed consent, in accordance with the local practices at each site.
Who cannot join
- Co-existing Condition:
- Patients with the following conditions or symptoms are excluded:
- History of cerebral toxoplasmosis or toxoplasmosis infection in any other organ or tissue.
- Coma.
- More than 72 hours of treatment for current episode of toxoplasmic encephalitis prior to study entry.
- Central nervous system (CNS) lymphoma.
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- Cerebral Kaposi's sarcoma.
- Active hepatitis or clinical jaundice.
- History of serious hypersensitivity or intolerance to any of the study drugs.
- Serum or cerebrospinal fluid (CSF) positive for cryptococcus antigen or culture.
- Malignancies requiring use of cytotoxic chemotherapy.
- Inability to take oral therapy reliably.
- Malabsorption syndrome.
- Concurrent Medication:
- Excluded:
- Opportunistic infection requiring either acute treatment or maintenance therapy with azithromycin, erythromycin or other macrolides, sulfonamides, amphotericin, dapsone, ganciclovir, antifolates, and other investigational agents except erythropoietin. For first 6 weeks of treatment, patients may not receive treatment with erythromycin (or other macrolides), sulfonamides, immunomodulators with the exception of alpha interferon, lymphocyte replacement, cytotoxic chemotherapy, dapsone, ganciclovir, rifampicin, coumadin, antiretrovirals, and investigational agents other than erythropoietin.
- Patients with the following are excluded:
- Negative HIV antibodies by a federally licensed ELISA, unless there is documentation of a previously positive HIV culture or p24 antigen.
- Infections of the central nervous system.
- Malignancies requiring the use of cytotoxic chemotherapy.
- Any medical or social condition that, in the opinion of the investigator, would adversely affect participation and/or compliance in this study.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Nassau County Med Ctr
East Meadow, New York, 11554
Los Angeles County - USC Med Ctr
Los Angeles, California, 90033
Univ of Miami School of Medicine
Miami, Florida, 331361013
Bellevue Hosp / New York Univ Med Ctr
New York, New York, 10016
Cornell Univ Med Ctr
New York, New York, 10021
SUNY - Stony Brook
Stony Brook, New York, 117948153
Bronx Municipal Hosp Ctr/Jacobi Med Ctr
The Bronx, New York, 10461
Montefiore Med Ctr / Bronx Municipal Hosp
The Bronx, New York, 10467
Bronx Veterans Administration / Mount Sinai Hosp
The Bronx, New York, 10468
Julio Arroyo
West Columbia, South Carolina, 29169
Univ of Massachusetts Med Ctr
Worcester, Massachusetts, 01655
About this study
Official title: A Dose-Escalation, Phase I/II Study of Oral Azithromycin and Pyrimethamine for the Treatment of Toxoplasmic Encephalitis in Patients With AIDS
To evaluate the effectiveness and toxicity of oral azithromycin and pyrimethamine as acute therapy for toxoplasmic encephalitis in AIDS patients. To assess the toxicity and effectiveness of azithromycin alone as maintenance therapy.
Encephalitis caused by Toxoplasma gondii is the most frequent cause of focal central nervous system infection in patients with AIDS. Untreated, the encephalitis is fatal. Standard treatment for toxoplasmic encephalitis is associated with serious adverse effects. Thus, alternative treatments are needed.
Read the detailed description
Encephalitis caused by Toxoplasma gondii is the most frequent cause of focal central nervous system infection in patients with AIDS. Untreated, the encephalitis is fatal. Standard treatment for toxoplasmic encephalitis is associated with serious adverse effects. Thus, alternative treatments are needed.
Patients with toxoplasmosis are given azithromycin at doses starting at the lowest dose for the first cohort, an intermediate dose for the second cohort, and a higher dose for the third cohort. Subsequent cohorts may receive azithromycin in increased dosage, if needed to determine the MTD. All patients also receive pyrimethamine. Folinic acid is also provided for as long as patients receive pyrimethamine. Patients are evaluated for clinical response to treatment at days 3, 7, and 14, and weekly for 6 weeks. Maintenance treatment with azithromycin continues for an additional 24 weeks. Patients who complete the study period without relapse or significant toxicity are offered continued therapy by the drug company and are followed for survival and relapse on a monthly basis for 1 year. After the MTD is determined, a subsequent cohort may be added for special studies.
- Conditions
- Toxoplasmosis, Cerebral, HIV Infections
- Being tested
- Azithromycin, Pyrimethamine, Leucovorin calcium
- Keywords
- Toxoplasmosis, Toxoplasma, Pyrimethamine, Leucovorin, Drug Evaluation, Drug Therapy, Combination, Encephalitis, Administration, Oral, Acquired Immunodeficiency Syndrome, Azithromycin
- Medical subject headings
- Toxoplasmosis, Cerebral, HIV Infections, Toxoplasmosis, Encephalitis, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzithromycinDrug
PyrimethamineDrug
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)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)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 PfizerThe 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 1
- Primary purpose
- Treatment
- Enrolment
- 45 participants
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Luft B, Study chairRemington J, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000966
- Sponsor's protocol ID
- ACTG 156
- Status last verified
- Oct 1994
- First submitted
- 2 Nov 1999
- Last updated
- 26 Aug 2008
- Results posted
- No
Publications
Saba J, Morlat P, Raffi F, Hazebroucq V, Joly V, Leport C, Vilde JL. Pyrimethamine plus azithromycin for treatment of acute toxoplasmic encephalitis in patients with AIDS. Eur J Clin Microbiol Infect Dis. 1993 Nov;12(11):853-6. doi: 10.1007/BF02000407.
PubMed 8112357. Kamarulzaman A, Hoy J. Effect of folinic acid on haematological toxicity during treatment of cerebral toxoplasmosis in patients with AIDS. Annu Conf Australas Soc HIV Med. 1995 Nov 16-19;7:68 (abstract no 68)
Jacobson JM, Hafner R, Remington J, Farthing C, Holden-Wiltse J, Bosler EM, Harris C, Jayaweera DT, Roque C, Luft BJ; ACTG 156 Study Team. Dose-escalation, phase I/II study of azithromycin and pyrimethamine for the treatment of toxoplasmic encephalitis in AIDS. AIDS. 2001 Mar 30;15(5):583-9. doi: 10.1097/00002030-200103300-00007.
PubMed 11316995
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dose-Escalation, Phase I/II Study of Oral Azithromycin and Pyrimethamine for the Treatment of Toxoplasmic Encephalitis in Patients With AIDS
- ClinicalTrials.gov ID
- NCT00000966
- Acronym / sponsor ID
- ACTG 156
- Conditions
- Toxoplasmosis, Cerebral, HIV Infections
- Keywords
- Toxoplasmosis, Toxoplasma, Pyrimethamine, Leucovorin, Drug Evaluation, Drug Therapy, Combination, Encephalitis, Administration, Oral
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- 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 evaluate the effectiveness and toxicity of oral azithromycin and pyrimethamine as acute therapy for toxoplasmic encephalitis in AIDS patients. To assess the toxicity and effectiveness of azithromycin alone as maintenance therapy.
Encephalitis caused by Toxoplasma gondii is the most frequent cause of focal central nervous system infection in patients with AIDS. Untreated, the encephalitis is fatal. Standard treatment for toxoplasmic encephalitis is associated with serious adverse effects. Thus, alternative treatments are needed.
Detailed description
Encephalitis caused by Toxoplasma gondii is the most frequent cause of focal central nervous system infection in patients with AIDS. Untreated, the encephalitis is fatal. Standard treatment for toxoplasmic encephalitis is associated with serious adverse effects. Thus, alternative treatments are needed.
Patients with toxoplasmosis are given azithromycin at doses starting at the lowest dose for the first cohort, an intermediate dose for the second cohort, and a higher dose for the third cohort. Subsequent cohorts may receive azithromycin in increased dosage, if needed to determine the MTD. All patients also receive pyrimethamine. Folinic acid is also provided for as long as patients receive pyrimethamine. Patients are evaluated for clinical response to treatment at days 3, 7, and 14, and weekly for 6 weeks. Maintenance treatment with azithromycin continues for an additional 24 weeks. Patients who complete the study period without relapse or significant toxicity are offered continued therapy by the drug company and are followed for survival and relapse on a monthly basis for 1 year. After the MTD is determined, a subsequent cohort may be added for special studies.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 13 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia (PCP).
- Allowed during maintenance period (weeks 7 - 24):
- Zidovudine and other antiretrovirals available through treatment IND mechanisms, ganciclovir, and maintenance doses of amphotericin (other investigational therapies require permission from the study chair), steroids for the treatment of acute PCP.
- Isoniazid (INH) only for patients already on INH.
- HIV infection or belong to high-risk group. Presumptive or definite diagnosis of toxoplasmic encephalitis.
Key exclusion criteria (21 listed)
- History of cerebral toxoplasmosis or toxoplasmosis infection in any other organ or tissue.
- Coma.
- More than 72 hours of treatment for current episode of toxoplasmic encephalitis prior to study entry.
- Central nervous system (CNS) lymphoma.
- Cerebral Kaposi's sarcoma.
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 |
|---|---|---|
| Azithromycin | Drug | – |
| Pyrimethamine | Drug | – |
| Leucovorin calcium | 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 26 Aug 2008.
- Background: PubMed 8112357Saba J, Morlat P, Raffi F, Hazebroucq V, Joly V, Leport C, Vilde JL. Pyrimethamine plus azithromycin for treatment of acute toxoplasmic encephalitis in patients with AIDS. Eur J Clin Microbiol Infect Dis. 1993 Nov;12(11):853-6. doi: 10.1007/BF02000407.
- Background. Kamarulzaman A, Hoy J. Effect of folinic acid on haematological toxicity during treatment of cerebral toxoplasmosis in patients with AIDS. Annu Conf Australas Soc HIV Med. 1995 Nov 16-19;7:68 (abstract no 68)
- Background: PubMed 11316995Jacobson JM, Hafner R, Remington J, Farthing C, Holden-Wiltse J, Bosler EM, Harris C, Jayaweera DT, Roque C, Luft BJ; ACTG 156 Study Team. Dose-escalation, phase I/II study of azithromycin and pyrimethamine for the treatment of toxoplasmic encephalitis in AIDS. AIDS. 2001 Mar 30;15(5):583-9. doi: 10.1097/00002030-200103300-00007.
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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.
Luft B study chair
Remington J study chair
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Azithromycin, Pyrimethamine and Leucovorin calcium in people with Toxoplasmosis, Cerebral and HIV Infections, run by Pfizer at 11 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 9 inclusion and 21 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 26 Aug 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 NCT00000966, which also lists 3 linked publications.
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 26 Aug 2008.