Prevention of Congenital Toxoplasmosis With Pyrimethamine + Sulfadiazine Versus Spiramycine During Pregnancy (TOXOGEST)

Assistance Publique - Hôpitaux de Paris

Status and phase: Completed; Phase 3

Conditions: Congenital Toxoplasmosis

Treatments: Drug: Spiramycine; Drug: Pyrimethamine/Sulfadiazine

Study type: Interventional

Funder types: Other

Identifiers

NCT01189448

2010-019972-65 (EudraCT Number)

P081234

Details and patient eligibility

About

Background : When a mother contracts toxoplasmosis during pregnancy, the parasite may be transmitted from to her unborn child. This results in congenital toxoplasmosis, which may cause damage to the eyes and nervous system of the child. To date, no method has been proved effective to prevent this transmission. In France, spiramycin is usually prescribed to women who have toxoplasma seroconversion in pregnancy, however its efficacy has not been determined. The standard treatment for toxoplasmosis is the combination of the antiparasitic drugs pyrimethamine and sulfadiazine, but this strategy has not been evaluated for the prevention of mother-to-child transmission.

Purpose : Randomized phase 3 trial to determine whether pyrimethamine + sulfadiazine is more effective than spiramycin to prevent congenital toxoplasmosis.

Full description

The protocol is a comparison of 2 strategies to prevent mother-to-child transmission of T. gondii following maternal seroconversion.

Screening for toxoplasmosis is mandatory in France. Patients with confirmed seroconversion will be eligible for the trial, after 14 weeks gestational age.

Participants will be randomly allocated to one of the treatment groups, and will receive open-label pyrimethamine + sulfadiazine or spiramycin.

The protocol will not change the usual procedures for prenatal diagnosis, nor will it change the management of infected fetuses and neonates.

Enrollment: 149 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• > 18 years old
• Toxoplasmosis infection acquired during the pregnancy documented by at least one negative serology in the first trimester and seroconversion with presence of specific IgG antibodies
• Gestational age > 14 weeks from last menstrual period
• Signature of informed consent

Exclusion criteria

• Lack of a documented negative serology during the pregnancy
• Antiparasitic therapy with spiramycin, pyrimethamine or sulfa drugs for more than 10 days after seroconversion and before randomization,
• Known allergy to any of the study drugs, serious allergic conditions or G6PD deficiency,
• Known hepatic or renal insufficiency,
• Other ongoing severe conditions in mother or fetus
• Lack of public health insurance

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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149 participants in 2 patient groups

Pyrimethamine/Sulfadiazine

Active Comparator group

Description:

Women who are enrolled and randomised in Pyrimethamine + sulfadiazine group : Pyrimethamine 50 mg once daily orally and sulfadiazine 1g tid. orally, with supplemental folinic acid 50 mg once a week.

Treatment:

Drug: Pyrimethamine/Sulfadiazine

Spiramycine

Active Comparator group

Description:

Spiramycin group : spiramycin 1g tid orally

Treatment:

Drug: Spiramycine