Prevention of Congenital Toxoplasmosis With Pyrimethamine + Sulfadiazine Versus Spiramycine During Pregnancy (TOXOGEST)
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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 |
- Rate of mother-to-child transmission [ Time Frame: Up to one year 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 Measure [ Time Frame: Up to one year 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: | September 2010 |
| Estimated Study Completion Date: | March 2015 |
| Estimated Primary Completion Date: | March 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:
|
|
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 |
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 7 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
Contacts and Locations| Contact: Laurent Mandelbrot, MD | +33 (0) 1 47 60 63 39 | laurent.mandelbrot@lmr.aphp.fr |
| 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 | |
| Contact: Laurence Salomon +33 (0)1 47 60 67 27 laurence.salomon@lmr.aphp.fr | |
| 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: | July 26, 2012 |
| 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:
|
Parasitic Diseases Central Nervous System Parasitic Infections Toxoplasmosis Toxoplasmosis, Congenital Coccidiosis Protozoan Infections Central Nervous System Protozoal 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 May 19, 2013