Pyrimethamine, Sulfadiazine, and Leucovorin in Treating Patients With Congenital Toxoplasmosis - Full Text View

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 II 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 IV

MedlinePlus related topics:

Toxoplasmosis

Drug Information available for:

Leucovorin Calcium Citrovorum factor Folinic acid calcium salt pentahydrate Leucovorin Pyrimethamine Calcium gluconate Spiramycin Sulfadiazine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Single Blind (Outcomes Assessor), Dose Comparison, Parallel Assignment, Safety/Efficacy Study

Official Title:	Phase II Randomized Study of Pyrimethamine, Sulfadiazine, and Leucovorin Calcium for Congenital Toxoplasmosis

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

Primary Outcome Measures:

Persistent motor abnormality [ Time Frame: Throughout life ] [ Designated as safety issue: Yes ]
Vision [ Time Frame: Throughout life ] [ Designated as safety issue: Yes ]
Hearing [ Time Frame: Throughout life ] [ Designated as safety issue: Yes ]
New chorioretinal lesion [ Time Frame: Throughout life ] [ Designated as safety issue: Yes ]
IQ less than 70 [ Time Frame: Throughout life ] [ Designated as safety issue: Yes ]
Decrease in IQ of greater than or equal to 15 points [ Time Frame: Throughout life ] [ 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
1: Experimental 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
2: Experimental 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 treated prenatally are randomized separately. 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.

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:

--Disease Characteristics-- 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

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

National Institute of Allergy and Infectious Diseases (NIAID)

University of Chicago

Investigators


Study Chair:	Rima McLeod	University of Chicago

More Information

Responsible Party:	University of Chicago ( Rima McLeod, MD Professor )
Study ID Numbers:	199/11837, UCCRC-08796, MRH-850410, UCRCC-08796
First Received:	October 18, 1999
Last Updated:	September 2, 2008
ClinicalTrials.gov Identifier:	NCT00004317
Health Authority:	United States: Federal Government

Keywords provided by Office of Rare Diseases (ORD):

immunologic disorders and infectious disorders

rare disease

toxoplasmosis

Study placed in the following topic categories:

Pyrimethamine

Protozoan Infections

Rare Diseases

Central Nervous System Diseases

Leucovorin

Toxoplasmosis, Congenital

Spiramycin

Toxoplasmosis

Folic Acid

Central Nervous System Infections

Infant, Newborn, Diseases

Parasitic Diseases

Sulfadiazine

Additional relevant MeSH terms:

Anti-Infective Agents

Antiprotozoal Agents

Vitamin B Complex

Molecular Mechanisms of Pharmacological Action

Coccidiosis

Growth Substances

Nervous System Diseases

Physiological Effects of Drugs

Enzyme Inhibitors

Folic Acid Antagonists

Central Nervous System Parasitic Infections

Pharmacologic Actions

Anti-Bacterial Agents

Antimalarials

Central Nervous System Protozoal Infections

Antiparasitic Agents

Therapeutic Uses

Vitamins

Micronutrients

Coccidiostats

ClinicalTrials.gov processed this record on November 20, 2008

Sponsors and Collaborators:	National Institute of Allergy and Infectious Diseases (NIAID) University of Chicago
Information provided by:	Office of Rare Diseases (ORD)
ClinicalTrials.gov Identifier:	NCT00004317