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

NCT ID: NCT00004317

Last Updated: 2009-05-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 600 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-07-31
• Study Completion Date: 2030-12-31

Brief 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.

Detailed 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.

Conditions

Toxoplasmosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

1

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.

Group Type: EXPERIMENTAL

Leucovorin calcium

Intervention Type: DRUG

See arm descriptions

Pyrimethamine

Intervention Type: DRUG

See arm descriptions

Spiramycin

Intervention Type: DRUG

Spiramycin is administered before the fetal diagnosis is made.

Sulfadiazine

Intervention Type: DRUG

See arm descriptions

2

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.

Group Type: EXPERIMENTAL

Leucovorin calcium

Intervention Type: DRUG

See arm descriptions

Pyrimethamine

Intervention Type: DRUG

See arm descriptions

Spiramycin

Intervention Type: DRUG

Spiramycin is administered before the fetal diagnosis is made.

Sulfadiazine

Intervention Type: DRUG

See arm descriptions

Interventions

Leucovorin calcium

See arm descriptions

Intervention Type: DRUG

Pyrimethamine

See arm descriptions

Intervention Type: DRUG

Spiramycin

Spiramycin is administered before the fetal diagnosis is made.

Intervention Type: DRUG

Sulfadiazine

See arm descriptions

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Chicago

OTHER

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

University of Chicago

Principal Investigators

Rima McLeod

Role: STUDY_CHAIR

University of Chicago

Locations

University of Chicago

Chicago, Illinois, United States

Site Status: RECRUITING

Countries

United States

Facility Contacts

Rima McLeod

Role: primary

773-834-4152

References

McLeod R, Boyer KM, Lee D, Mui E, Wroblewski K, Karrison T, Noble AG, Withers S, Swisher CN, Heydemann PT, Sautter M, Babiarz J, Rabiah P, Meier P, Grigg ME; Toxoplasmosis Study Group. Prematurity and severity are associated with Toxoplasma gondii alleles (NCCCTS, 1981-2009). Clin Infect Dis. 2012 Jun;54(11):1595-605. doi: 10.1093/cid/cis258. Epub 2012 Apr 11.

Reference Type: DERIVED

PMID: 22499837 (View on PubMed)

Other Identifiers

UCCRC-08796

Identifier Type: -

Identifier Source: secondary_id

MRH-850410

Identifier Type: -

Identifier Source: secondary_id

UCRCC-08796

Identifier Type: -

Identifier Source: secondary_id

199/11837

Identifier Type: -

Identifier Source: org_study_id

NCT00170599

Identifier Type: -

Identifier Source: nct_alias