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

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Completed

CT.gov ID

NCT01189448

Collaborator

(none)

149

Enrollment

Location

Arms

Duration (Months)

2.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Congenital Toxoplasmosis	Drug: Pyrimethamine/Sulfadiazine Drug: Spiramycine	Phase 3

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

149 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Multicenter, Randomized Clinical Trial to Compare the Efficacy and Tolerance of Prenatal Therapy With Pyrimethamine + Sulfadiazine vs Spiramycine to Reduce Vertical Transmission of Toxoplasma Gondii Following Primary Infection in Pregnancy

Study Start Date :

Nov 1, 2010

Actual Primary Completion Date :

Jul 1, 2014

Actual Study Completion Date :

Apr 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Pyrimethamine/Sulfadiazine 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.	Drug: Pyrimethamine/Sulfadiazine Pyrimethamine + sulfadiazine group : Pyrimethamine 50 mg once daily orally and sulfadiazine 1g tid. orally, with supplemental folinic acid 50 mg once a week. Follow-up includes clinical and biological tolerance, according to usual recommendations. Monthly fetal ultrasound is performed. Prenatal diagnosis with amniocentesis is offered after 18 weeks gestation, usually 4 weeks after the maternal infection. Treatment is be stopped or changed in case of toxicity. If prenatal diagnosis shows fetal infection with T. gondii, management is to be determined by the clinicians with the patient. If the prenatal diagnosis is negative the treatment can be stopped in order to reduce the risk of intolerance, providing that the mother receives at least 4 weeks of therapy. Other Names: Pyrimethamine = Malocide® Sulfadiazine = Adiazine®
Active Comparator: Spiramycine Spiramycin group : spiramycin 1g tid orally	Drug: Spiramycine Spiramycin group : spiramycin 1g tid orally Follow-up includes clinical and biological tolerance, according to usual recommendations. Monthly fetal ultrasound is performed. Prenatal diagnosis with amniocentesis is offered after 18 weeks gestation, usually 4 weeks after the maternal infection. Treatment is be stopped or changed in case of toxicity. If prenatal diagnosis shows fetal infection with T. gondii, management is to be determined by the clinicians with the patient. If the prenatal diagnosis is negative the treatment is continued according to usual procedures Other Names: Spiramycine = Rovamycine®

Arm

Intervention/Treatment

Active Comparator: Pyrimethamine/Sulfadiazine

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.

Drug: Pyrimethamine/Sulfadiazine

Pyrimethamine + sulfadiazine group : Pyrimethamine 50 mg once daily orally and sulfadiazine 1g tid. orally, with supplemental folinic acid 50 mg once a week. Follow-up includes clinical and biological tolerance, according to usual recommendations. Monthly fetal ultrasound is performed. Prenatal diagnosis with amniocentesis is offered after 18 weeks gestation, usually 4 weeks after the maternal infection. Treatment is be stopped or changed in case of toxicity. If prenatal diagnosis shows fetal infection with T. gondii, management is to be determined by the clinicians with the patient. If the prenatal diagnosis is negative the treatment can be stopped in order to reduce the risk of intolerance, providing that the mother receives at least 4 weeks of therapy.

Other Names:

Pyrimethamine = Malocide®

Sulfadiazine = Adiazine®

Active Comparator: Spiramycine

Spiramycin group : spiramycin 1g tid orally

Drug: Spiramycine

Spiramycin group : spiramycin 1g tid orally Follow-up includes clinical and biological tolerance, according to usual recommendations. Monthly fetal ultrasound is performed. Prenatal diagnosis with amniocentesis is offered after 18 weeks gestation, usually 4 weeks after the maternal infection. Treatment is be stopped or changed in case of toxicity. If prenatal diagnosis shows fetal infection with T. gondii, management is to be determined by the clinicians with the patient. If the prenatal diagnosis is negative the treatment is continued according to usual procedures

Other Names:

Spiramycine = Rovamycine®

Outcome Measures

Primary Outcome Measures

Rate of mother-to-child transmission [Up to six months after birth]
Rate of mother-to-child transmission of toxoplasma gondii, determined by PCR on amniocentesis and/or synthesis of specific antibodies by the neonate

Secondary Outcome Measures

Secondary Outcome Measure [Up to six months after birth]
Mother-to-child transmission rate according to the time between primary infection and start of therapy Tolerance in mothers and neonates (grade 3-4 toxicities) Severity of infection at birth in case of congenital toxoplasmosis (parasite load in amniotic fluid, clinical and biological signs)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts 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