Chicago, Illinois 60637


Purpose:

RATIONALE: Congenital toxoplasmosis is an infection caused by the parasitic organism Toxoplasma gondii, and it may be passed from an infected mother to her unborn child. The mother may have mild symptoms or no symptoms; the fetus, however, may experience damage to the eyes, nervous system, skin, and ears. The newborn may have a low birth weight, enlarged liver and spleen, jaundice, anemia, petechiae, and eye damage. Giving the antiparasitic drugs pyrimethamine and sulfadiazine is standard treatment for congenital toxoplasmosis, but it is not yet known which regimen of pyrimethamine is most effective for the disease. PURPOSE: Randomized phase IV trial to determine which regimen of pyrimethamine is most effective when combined with sulfadiazine and leucovorin in treating patients who have congenital toxoplasmosis.


Study summary:

PROTOCOL OUTLINE: Infants are randomly assigned to 1 of 2 treatment groups. Patients are stratified by disease severity, chorioretinitis, prenatal treatment, and certainty of diagnosis at birth. One group of infants is treated with a loading dose of oral pyrimethamine followed by a higher dose for the first two months then a lower dose for the remainder of the 12 months. Sulfadiazine and leucovorin calcium are also given orally for 12 months. The pyrimethamine loading dose is omitted if prior prenatal therapy was given. Another group of infants is treated with a higher dose of oral pyrimethamine for the first 6 months and then the lower dose for the remainder of the 12 months. Sulfadiazine and leucovorin calcium are administered concurrently. Infected fetuses of pregnant women are nonrandomly assigned to treatment with pyrimethamine, sulfadiazine, and leucovorin calcium after the first trimester. Spiramycin is administered before the fetal diagnosis is made. Concurrent prednisone for active retinal inflammation or elevated cerebrospinal fluid protein is allowed. Collaborating physicians will also refer historical controls, who have not been treated in the first year of life or who received one month or less therapy, and are older than one year. Absence of treatment in the first year of life will be due to parental preference, prior inadequate follow-up by the family physicians, or lack of detection or treatment of eye disease before the age of one year in otherwise asymptomatic children. These historical, untreated patients (who enter the study when they are older than one year) will be compared with treated children in the randomized study. These historical patients will not be randomized. Any abnormality requiring treatment (e.g., active chorioretinitis) in any child (including historical patients) will be treated. All infants are followed at birth, then at age 1, 3.5, 5, 7.5, 10, 15, and 20.


Criteria:

PROTOCOL ENTRY CRITERIA: - Infants with congenital toxoplasmosis Toxoplasma gondii confirmed prior to age 2.5 months - Pregnant women with evidence of toxoplasma infection by clinical observation and amniotic fluid sampling - Acute infection acquired during gestation with evidence of fetal infection - Untreated older children entered as controls - Asymptomatic congenital toxoplasmosis - Age more than 1 year - No treatment within the first year of life - No more than 1 month of prior therapy


Study is Available At:


Original ID:

199/11837


NCT ID:

NCT00004317


Secondary ID:

UCCRC-08796


Study Acronym:


Brief Title:

Pyrimethamine, Sulfadiazine, and Leucovorin in Treating Patients With Congenital Toxoplasmosis


Official Title:

Phase IV Randomized Study of Pyrimethamine, Sulfadiazine, and Leucovorin Calcium for Congenital Toxoplasmosis


Overall Status:

Recruiting


Study Phase:

Phase 4


Genders:

Both


Minimum Age:

N/A


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Office of Rare Diseases (ORD)


Oversight Authority:

United States: Federal Government


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Allocation: Randomized, Endpoint Classification:


Number of Arms:

2


Number of Groups:

0


Total Enrollment:

600


Enrollment Type:

Anticipated


Overall Contact Information

Official Name:Rima McLeod
Study Chair
University of Chicago

Study Dates

Start Date:July 2000
Completion Date:December 2030
Completion Type:Anticipated
Primary Completion Date:December 2030
Primary Completion Type:Anticipated
Verification Date:May 2009
Last Changed Date:May 13, 2009
First Received Date:October 18, 1999

Study Outcomes

Outcome Type:Primary Outcome
Measure:Persistent motor abnormality
Time Frame:At pre-specified time points
Safety Issues:True
Outcome Type:Primary Outcome
Measure:Vision
Time Frame:At pre-specified time points
Safety Issues:True
Outcome Type:Primary Outcome
Measure:Hearing
Time Frame:At pre-specified time points
Safety Issues:True
Outcome Type:Primary Outcome
Measure:New chorioretinal lesion
Time Frame:At pre-specified time points
Safety Issues:True
Outcome Type:Primary Outcome
Measure:IQ less than 70
Time Frame:At pre-specified time points
Safety Issues:True
Outcome Type:Primary Outcome
Measure:Decrease in IQ of greater than or equal to 15 points
Time Frame:At pre-specified time points
Safety Issues:True

Study Interventions

Intervention Type:Drug
Name:Leucovorin calcium
Description:See arm descriptions
Arm Name:1
Intervention Type:Drug
Name:Pyrimethamine
Description:See arm descriptions
Arm Name:1
Intervention Type:Drug
Name:Spiramycin
Description:Spiramycin is administered before the fetal diagnosis is made.
Arm Name:1
Intervention Type:Drug
Name:Sulfadiazine
Description:See arm descriptions
Arm Name:1

Study Arms

Study Arm Type:Experimental
Arm Name:1
Description:This group of infants is treated with a loading dose of oral pyrimethamine followed by a higher dose for the first two months then a lower dose for the remainder of the 12 months. Sulfadiazine and leucovorin calcium are also given orally for 12 months. The pyrimethamine loading dose is omitted if prior prenatal therapy was given.
Study Arm Type:Experimental
Arm Name:2
Description:This group of infants is treated with a higher dose of oral pyrimethamine for the first 6 months and then the lower dose for the remainder of the 12 months. Sulfadiazine and leucovorin calcium are administered concurrently.

Study Agencies

Agency Class:NIH
Agency Type:Lead Sponsor
Agency Name:National Institute of Allergy and Infectious Diseases (NIAID)
Agency Class:Other
Agency Type:Collaborator
Agency Name:University of Chicago

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: November 18, 2019

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