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

Primary Purpose

Congenital Toxoplasmosis

Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Pyrimethamine/Sulfadiazine
Spiramycine
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Congenital Toxoplasmosis focused on measuring Congenital Toxoplasmosis,, Pregnancy,, prenatal diagnosis,, mother-to-child transmission,, prevention,, spiramycine,, pyrimethamine-sulfadiazine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept 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

Sites / Locations

  • Hôpital Louis Mourier

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Pyrimethamine/Sulfadiazine

Spiramycine

Arm 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.

Spiramycin group : spiramycin 1g tid orally

Outcomes

Primary Outcome Measures

Rate of mother-to-child transmission
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
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)

Full Information

First Posted
August 25, 2010
Last Updated
September 28, 2016
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT01189448
Brief Title
Prevention of Congenital Toxoplasmosis With Pyrimethamine + Sulfadiazine Versus Spiramycine During Pregnancy
Acronym
TOXOGEST
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 Type
Interventional

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
November 2010 (undefined)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
April 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congenital Toxoplasmosis
Keywords
Congenital Toxoplasmosis,, Pregnancy,, prenatal diagnosis,, mother-to-child transmission,, prevention,, spiramycine,, pyrimethamine-sulfadiazine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
149 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pyrimethamine/Sulfadiazine
Arm Type
Active Comparator
Arm 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.
Arm Title
Spiramycine
Arm Type
Active Comparator
Arm Description
Spiramycin group : spiramycin 1g tid orally
Intervention Type
Drug
Intervention Name(s)
Pyrimethamine/Sulfadiazine
Other Intervention Name(s)
Pyrimethamine = Malocide®, Sulfadiazine = Adiazine®
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Spiramycine
Other Intervention Name(s)
Spiramycine = Rovamycine®
Intervention Description
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
Primary Outcome Measure Information:
Title
Rate of mother-to-child transmission
Description
Rate of mother-to-child transmission of toxoplasma gondii, determined by PCR on amniocentesis and/or synthesis of specific antibodies by the neonate
Time Frame
Up to six months after birth
Secondary Outcome Measure Information:
Title
Secondary Outcome Measure
Description
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)
Time Frame
Up to six months after birth

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Laurent Mandelbrot, MD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Louis Mourier
City
Colombes
State/Province
Hauts-de-Saine
ZIP/Postal Code
92700
Country
France

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

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

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