Trial record 19 of 289 for:    Open Studies | "Parasitic Diseases"

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
  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.


Condition Intervention Phase
Toxoplasmosis
Drug: Leucovorin calcium
Drug: Pyrimethamine
Drug: Spiramycin
Drug: Sulfadiazine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase IV Randomized Study of Pyrimethamine, Sulfadiazine, and Leucovorin Calcium for Congenital Toxoplasmosis

Resource links provided by NLM:


Further study details as provided by Office of Rare Diseases (ORD):

Primary Outcome Measures:
  • 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 ]

Estimated Enrollment: 600
Study Start Date: July 2000
Estimated Study Completion Date: December 2030
Estimated Primary Completion Date: December 2030 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004317

Locations
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Rima McLeod    773-834-4152      
Sponsors and Collaborators
University of Chicago
Investigators
Study Chair: Rima McLeod University of Chicago
  More Information

No publications provided by Office of Rare Diseases (ORD)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Rima McLeod, MD Professor, University of Chicago
ClinicalTrials.gov Identifier: NCT00004317     History of Changes
Obsolete Identifiers: NCT00170599
Other Study ID Numbers: 199/11837, UCCRC-08796, MRH-850410, UCRCC-08796
Study First Received: October 18, 1999
Last Updated: May 13, 2009
Health Authority: United States: Federal Government

Keywords provided by Office of Rare Diseases (ORD):
immunologic disorders and infectious disorders
rare disease
toxoplasmosis

Additional relevant MeSH terms:
Parasitic Diseases
Central Nervous System Parasitic Infections
Toxoplasmosis
Toxoplasmosis, Congenital
Coccidiosis
Protozoan Infections
Central Nervous System Protozoal Infections
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Infant, Newborn, Diseases
Calcium, Dietary
Leucovorin
Levoleucovorin
Pyrimethamine
Spiramycin
Sulfadiazine
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antidotes
Protective Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 28, 2014