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

Sponsor
National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
Overall Status
Recruiting
CT.gov ID
NCT00004317
Collaborator
University of Chicago (Other)
600
1
2
365
1.6

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 4

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
600 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Phase IV Randomized Study of Pyrimethamine, Sulfadiazine, and Leucovorin Calcium for Congenital Toxoplasmosis
Study Start Date :
Jul 1, 2000
Anticipated Primary Completion Date :
Dec 1, 2030
Anticipated Study Completion Date :
Dec 1, 2030

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: Leucovorin calcium
See arm descriptions

Drug: Pyrimethamine
See arm descriptions

Drug: Spiramycin
Spiramycin is administered before the fetal diagnosis is made.

Drug: Sulfadiazine
See arm descriptions

Experimental: 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.

Drug: Leucovorin calcium
See arm descriptions

Drug: Pyrimethamine
See arm descriptions

Drug: Spiramycin
Spiramycin is administered before the fetal diagnosis is made.

Drug: Sulfadiazine
See arm descriptions

Outcome Measures

Primary Outcome Measures

  1. Persistent motor abnormality [At pre-specified time points]

  2. Vision [At pre-specified time points]

  3. Hearing [At pre-specified time points]

  4. New chorioretinal lesion [At pre-specified time points]

  5. IQ less than 70 [At pre-specified time points]

  6. Decrease in IQ of greater than or equal to 15 points [At pre-specified time points]

Eligibility Criteria

Criteria

Ages Eligible for Study:
N/A and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 University of Chicago Chicago Illinois United States 60637

Sponsors and Collaborators

  • National Institute of Allergy and Infectious Diseases (NIAID)
  • University of Chicago

Investigators

  • Study Chair: Rima McLeod, University of Chicago

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
, ,
ClinicalTrials.gov Identifier:
NCT00004317
Other Study ID Numbers:
  • 199/11837
  • UCCRC-08796
  • MRH-850410
  • UCRCC-08796
  • NCT00170599
First Posted:
Oct 19, 1999
Last Update Posted:
May 14, 2009
Last Verified:
May 1, 2009

Study Results

No Results Posted as of May 14, 2009