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

This study is currently recruiting participants.
Verified November 2013 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01189448
First received: August 25, 2010
Last updated: November 7, 2013
Last verified: November 2013
  Purpose

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 Intervention Phase
Congenital Toxoplasmosis
Drug: Pyrimethamine/Sulfadiazine
Drug: Spiramycine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Rate of mother-to-child transmission [ Time Frame: Up to six months after birth ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to six months after birth ] [ Designated as safety issue: No ]
    • 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)


Estimated Enrollment: 330
Study Start Date: November 2010
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Spiramycine = Rovamycine®

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01189448

Contacts
Contact: Laurent Mandelbrot, MD +33 (0) 1 47 60 63 39 laurent.mandelbrot@lmr.aphp.fr

Locations
France
Hôpital Louis Mourier Recruiting
Colombes, Hauts-de-Saine, France, 92700
Contact: Laurent Mandelbrot, MD    +33 (0) 1 47 60 63 39    laurent.mandelbrot@lmr.aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Laurent Mandelbrot, MD Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01189448     History of Changes
Other Study ID Numbers: P081234, 2010-019972-65
Study First Received: August 25, 2010
Last Updated: November 7, 2013
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Congenital Toxoplasmosis,
Pregnancy,
prenatal diagnosis,
mother-to-child transmission,
prevention,
spiramycine,
pyrimethamine-sulfadiazine

Additional relevant MeSH terms:
Toxoplasmosis
Toxoplasmosis, Congenital
Coccidiosis
Protozoan Infections
Parasitic Diseases
Central Nervous System Protozoal Infections
Central Nervous System Parasitic Infections
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Infant, Newborn, Diseases
Pyrimethamine
Spiramycin
Sulfadiazine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents
Coccidiostats

ClinicalTrials.gov processed this record on April 16, 2014