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

NCT00004317 | Recruiting Phase 4 DMC

• 4 other identifiers: 199/11837UCCRC-08796MRH-850410UCRCC-08796
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 1

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.

Conditions

Toxoplasmosis

Keywords

immunologic disorders and infectious disorders; rare disease; toxoplasmosis

Outcome Measures

Primary Outcomes (6)

• Persistent motor abnormality

  At pre-specified time points

• Vision

  At pre-specified time points

• Hearing

  At pre-specified time points

• New chorioretinal lesion

  At pre-specified time points

• IQ less than 70

  At pre-specified time points

• Decrease in IQ of greater than or equal to 15 points

  At pre-specified time points

Study Arms (2)

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; Drug: Pyrimethamine; Drug: Spiramycin; Drug: Sulfadiazine

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; Drug: Pyrimethamine; Drug: Spiramycin; Drug: Sulfadiazine

Interventions

Leucovorin calcium DRUG

See arm descriptions

1; 2

Pyrimethamine DRUG

See arm descriptions

1; 2

Spiramycin DRUG

Spiramycin is administered before the fetal diagnosis is made.

1; 2

Sulfadiazine DRUG

See arm descriptions

1; 2

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

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

Study Sites (1)

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 22499837 DERIVED

MeSH Terms

Conditions

Toxoplasmosis; Immune System Diseases; Communicable Diseases; Rare Diseases

Interventions

Leucovorin; Pyrimethamine; Spiramycin; Sulfadiazine

Condition Hierarchy (Ancestors)

Coccidiosis; Protozoan Infections; Parasitic Diseases; Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Pyrimidines; Heterocyclic Compounds, 1-Ring; Leucomycins; Macrolides; Polyketides; Lactones; Organic Chemicals; Benzenesulfonamides; Sulfonamides; Amides; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds

Study Officials

• Rima McLeod

  University of Chicago

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: October 18, 1999
• First Posted: October 19, 1999
• Study Start: July 1, 2000
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: May 14, 2009

Record last verified: 2009-05

Locations

US (1)