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

19:45 EDT 26th March 2015 | BioPortfolio


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.

Study Design

Allocation: Randomized, Control: Dose Comparison, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment




Leucovorin calcium, Pyrimethamine, Spiramycin, Sulfadiazine


University of Chicago
United States




Office of Rare Diseases (ORD)

Results (where available)

View Results


Clinical Trials [596 Associated Clinical Trials listed on BioPortfolio]

Primary Prophylaxis of Cerebral Toxoplasmosis in HIV-Infected Patients

To evaluate the effectiveness of pyrimethamine (given with leucovorin calcium versus placebo (an inactive substance) for the primary prophylaxis (prevention) of cerebral toxoplasmosis in H...

A Randomized Prospective Study of Pyrimethamine Therapy for Prevention of Toxoplasmic Encephalitis in HIV-Infected Individuals With Serologic Evidence of Latent Toxoplasma Gondii Infection

To evaluate pyrimethamine as a prophylactic agent against toxoplasmic encephalitis in individuals who are coinfected with HIV and latent Toxoplasma gondii. Toxoplasmic encephalitis is a m...

A Study of Azithromycin Plus Pyrimethamine in the Treatment of a Brain Infection in Patients With AIDS

To evaluate the effectiveness and toxicity of oral azithromycin and pyrimethamine as acute therapy for toxoplasmic encephalitis in AIDS patients. To assess the toxicity and effectiveness o...

Toxoplasmic Encephalitis in Patients With AIDS. Treatment and Prevention of Relapse

To compare pyrimethamine and intravenous (IV) clindamycin vs. pyrimethamine and sulfonamides in the treatment of AIDS patients with central nervous system (CNS) Toxoplasma gondii.

Open-Label "Compassionate" Use Study of Spiramycin for the Treatment of Diarrhea Due to Chronic Cryptosporidiosis in Immunocompromised Patients

This protocol provides for the availability of spiramycin under compassionate-use conditions for the treatment of chronic diarrhea due to cryptosporidium in patients with a compromised imm...

PubMed Articles [1893 Associated PubMed Articles listed on BioPortfolio]

Spiramycin/cotrimoxazole versus pyrimethamine/sulfonamide and spiramycin alone for the treatment of toxoplasmosis in pregnancy.

Objective:To compare the effectiviness of spiramycin/cotrimoxazole (Sp/C) versus pyrimethamine/sulfonamide (Pyr/Sul) and spiramycin alone (Spy) on mother-to-child transmission of toxoplasmosis infecti...

Multidisciplinary approach to congenital Toxoplasma infection: an Italian nationwide survey.

Italy provides a free voluntary serological screening for toxoplasmosis in pregnancy supported by public health system, as there is an estimated congenital toxoplasmosis rate of 1-2/10,000. The aim of...

Chemical oxidation of sulfadiazine by the Fenton process: Kinetics, pathways, toxicity evaluation.

This paper investigated sulfadiazine oxidation by the Fenton process under various reaction conditions. The reaction conditions tested in the experiments included the initial pH value of reaction solu...

Effects of latent toxoplasmosis on autoimmune thyroid diseases in pregnancy.

Toxoplasmosis, one of the most common zoonotic diseases worldwide, can induce various hormonal and behavioural alterations in infected hosts, and its most common form, latent toxoplasmosis, influences...

Diclazuril Protects against Maternal Gastrointestinal Syndrome and Congenital Toxoplasmosis.

Toxoplasmosis is a common cause of foodborne, gastrointestinal and congenital syndrome with particularly severe or unknown health consequences. There is no safe and effective preventive or therapeutic...

Medical and Biotech [MESH] Definitions

One of the short-acting SULFONAMIDES used in combination with PYRIMETHAMINE to treat toxoplasmosis in patients with acquired immunodeficiency syndrome and in newborns with congenital infections.

One of the FOLIC ACID ANTAGONISTS that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis.

The active metabolite of FOLIC ACID. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid.

Infection caused by the protozoan parasite TOXOPLASMA in which there is extensive connective tissue proliferation, the retina surrounding the lesions remains normal, and the ocular media remain clear. Chorioretinitis may be associated with all forms of toxoplasmosis, but is usually a late sequel of congenital toxoplasmosis. The severe ocular lesions in infants may lead to blindness.

Antibacterial used topically in burn therapy.

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