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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2009 by Office of Rare Diseases (ORD)
Sponsor:
Collaborator:
University of Chicago
Information provided by:
Office of Rare Diseases (ORD)
ClinicalTrials.gov Identifier:
NCT00004317
First received: October 18, 1999
Last updated: May 13, 2009
Last verified: May 2009

October 18, 1999
May 13, 2009
July 2000
December 2030   (final data collection date for primary outcome measure)
  • Persistent motor abnormality [ Time Frame: At pre-specified time points ] [ Designated as safety issue: Yes ]
  • Vision [ Time Frame: At pre-specified time points ] [ Designated as safety issue: Yes ]
  • Hearing [ Time Frame: At pre-specified time points ] [ Designated as safety issue: Yes ]
  • New chorioretinal lesion [ Time Frame: At pre-specified time points ] [ Designated as safety issue: Yes ]
  • IQ less than 70 [ Time Frame: At pre-specified time points ] [ Designated as safety issue: Yes ]
  • Decrease in IQ of greater than or equal to 15 points [ Time Frame: At pre-specified time points ] [ Designated as safety issue: Yes ]
Not Provided
Complete list of historical versions of study NCT00004317 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Pyrimethamine, Sulfadiazine, and Leucovorin in Treating Patients With Congenital Toxoplasmosis
Phase IV Randomized Study of Pyrimethamine, Sulfadiazine, and Leucovorin Calcium for Congenital Toxoplasmosis

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Toxoplasmosis
  • 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: 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.
    Interventions:
    • Drug: Leucovorin calcium
    • Drug: Pyrimethamine
    • Drug: Spiramycin
    • Drug: Sulfadiazine
  • 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.
    Interventions:
    • Drug: Leucovorin calcium
    • Drug: Pyrimethamine
    • Drug: Spiramycin
    • Drug: Sulfadiazine
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
600
December 2030
December 2030   (final data collection date for primary outcome measure)

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
Both
Not Provided
No
United States
 
NCT00004317
199/11837, UCCRC-08796, MRH-850410, UCRCC-08796
Yes
Rima McLeod, MD Professor, University of Chicago
National Institute of Allergy and Infectious Diseases (NIAID)
University of Chicago
Study Chair: Rima McLeod University of Chicago
Office of Rare Diseases (ORD)
May 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP