Assessment of Two Therapeutic Strategies in the Treatment of Children With Congenital Toxoplasmosis (TOSCANE)

Multicentre, Randomised Study to Determine the Relative Efficacy of Two Therapeutic Strategies in the Treatment of Children With Congenital Toxoplasmosis

Toxoplasmosis is a benign disease in healthy adults, but can be serious in the case of contamination during pregnancy: the parasite can pass through the placental barrier and infect the foetus. The severity of congenital infection varies, but in France, where maternal seroconversions during pregnancy are treated, the manifestations of the disease are often infraclinical at birth and only appear during the first years of life in the form of retinochoroiditis. In order to prevent long-term sequellae, children with confirmed congenital toxoplasmosis (TC) are treated with pyrimethamine combined with either sulfadiazine or sulfadoxine (Fansidar®). The relative efficacy of these two combinations has not yet been evaluated. Moreover, there is no consensus about the duration of the treatment, which varies, in France, from 12 to 24 months depending on the centre. Compared with the duration of parasitaemia in non-treated children, which can persist for up to 4 weeks, these treatments are very long. They are also far longer than the 3 months of treatment, which is in accordance with the World Health Organization (WHO) recommendations, given in Denmark to infants identified as being infected with the parasite during neonatal screening. A one-year treatment was developed in the United States, but it mainly concerns only symptomatic children, given the absence of generalised screening in the United States of America (USA). We have no arguments to justify the use of treatments lasting one year or more in children with asymptomatic or mildly-symptomatic TC. As these treatments carry certain risks, which may be severe, notably with regard to haematological or skin conditions, they have to be supervised closely with biological tests, which adds further constraints for both the children and their parents and increases the cost to health care systems.

Study Overview

• Status: Terminated
• Conditions: Congenital Toxoplasmosis
• Intervention / Treatment: Procedure: registered length of treatment; Procedure: reducing treatment to 3 months

• Study Type: Interventional
• Enrollment (Actual): 302
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Valérie JAVERLIAC; Phone Number: 33 04 27 85 77 24; Email: valerie.javerliac@chu-lyon.fr

Study Locations

• France
  • Paris, France, 75015
    • Hôpital d'Enfants Armand Trousseau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 6 months (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Children meeting the following criteria can be included:

• Non-severe congenital toxoplasmosis diagnosed in utero or in the first 3 months of life, whether or not in utero treatment was given
• Treated for 3 months with pyrimethamine combined with sulfamides.
• age from 3 to 6 months (> 2 months and < 7 months)

Diagnostic criteria for congenital toxoplasmosis:

• antenatal period: positive Polymerase Chain Reaction (PCR) on the amniotic fluid or positive mouse inoculation for the amniotic fluid
• postnatal period: presence of specific Immunoglobuline M (IgM) and/or Immunoglobuline A (IgA), positive Western Blot Chemistry (WBC), increase in Immunoglobuline G (IgG).

Severe congenital toxoplasmosis is defined by the presence at birth of at least one of the following signs: > or egal 3 cerebral calcifications, hydrocephaly, microcephaly, convulsions, microphtalmy.

Informed consent must be provided by both parents.

Exclusion Criteria:

Children with the following cannot be included:

• a severe form of congenital toxoplasmosis
• inflammatory retinal disease at inclusion or in whom the treatment is contra-indicated (history of hypersensitivity to one of the components, severe renal or hepatic insufficiency, a history of hepatitis linked to treatment with Fansidar®).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 12 months	Procedure: registered length of treatment; The treatment procedure will follow the actual recommandation
Experimental: 3 months	Procedure: reducing treatment to 3 months; The treatment will be stopped after 3 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
episode of retinochoroiditis	Time to the onset of a first episode of retinochoroiditis in the two years of the study (or the onset of a new episode in a child known to already have had at least one lesion), evaluated on a fundus examination using RetCam®.	2 years

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Dijon
• Investigators: Study Director: Christine BINQUET, MD, CHU Dijon

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2010
• Primary Completion (Actual): January 26, 2017
• Study Completion (Actual): April 7, 2022

Study Registration Dates

• First Submitted: September 15, 2010
• First Submitted That Met QC Criteria: September 15, 2010
• First Posted (Estimated): September 16, 2010

Study Record Updates

• Last Update Posted (Estimated): February 22, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Infections; Infant, Newborn, Diseases; Central Nervous System Infections; Parasitic Diseases; Coccidiosis; Protozoan Infections; Central Nervous System Parasitic Infections; Central Nervous System Protozoal Infections; Toxoplasmosis; Toxoplasmosis, Congenital
• Other Study ID Numbers: 2009-016528-30