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

Toxoplasmosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00004317
• Other study ID #: 199/11837
• Secondary ID: UCCRC-08796MRH-8
• Status: Recruiting
• Phase: Phase 4
• First received: October 18, 1999
• Last updated: May 13, 2009
• Start date: July 2000
• Est. completion date: December 2030

Study information

• Verified date: May 2009
• Source: Office of Rare Diseases (ORD)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Other known NCT identifiers

• NCT00170599

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: December 2030
• Est. primary completion date: December 2030
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Toxoplasmosis
• Toxoplasmosis, Congenital

Intervention

Drug:
• Leucovorin calcium
See arm descriptions
• Pyrimethamine
See arm descriptions
• Spiramycin
Spiramycin is administered before the fetal diagnosis is made.
• Sulfadiazine
See arm descriptions

Locations

Country	Name	City	State
United States	University of Chicago	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	University of Chicago

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Persistent motor abnormality		At pre-specified time points	Yes
Primary	Vision		At pre-specified time points	Yes
Primary	Hearing		At pre-specified time points	Yes
Primary	New chorioretinal lesion		At pre-specified time points	Yes
Primary	IQ less than 70		At pre-specified time points	Yes
Primary	Decrease in IQ of greater than or equal to 15 points		At pre-specified time points	Yes