Long Term Safety of Clopidogrel in Neonates/Infants With Systemic to Pulmonary Artery Shunt Palliation

Study Overview
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Brief Summary
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This study is the extension of the CLARINET study [NCT00396877 -EFC5314] in neonates or infants with cyanotic congenital heart disease palliated with a systemic-to-pulmonary artery shunt. The primary objective was to assess the safety up to 18 months of age of the extended use of Clopidogrel 0.2 mg/kg/day in patients for whom the shunt was still in place at one year of age. The secondary objective was to assess the efficacy on the occurrence of shunt thrombosis requiring intervention or any death.

Detailed Description
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Patients remained in the treatment group to which they were originally allocated for the CLARINET study and continued blindly their treatment (0.2 mg/kg/day of clopidogrel or placebo) up to the occurrence of shunt thrombosis, next surgical procedure for correction of the congenital heart disease, death, or 18 months of age, whichever came first. The maximum treatment duration were 6 months.

Official Title
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Long Term Safety Study in Patients Included in the CLARINET Study With Cyanotic Congenital Heart Disease Palliated With a Systemic-to-pulmonary Artery Shunt and for Whom the Shunt is Still in Place at One Year of Age

Conditions
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Heart Defects, Congenital

Intervention / Treatment
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* Drug: Clopidogrel
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients randomized in the CLARINET study, Still receiving the study drug, Palliative systemic-to-pulmonary artery shunt still in place at 1 year of age, Investigator's decision to continue based on his/her judgment of the expected benefit / risk of continuing treatment with study drug, Signed informed consent to participate in the long-term safety study.

Ages Eligible for Study
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Minimum Age: 12 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>0.2 mL/kg/day matching placebo solution once daily. | Drug: placebo<br>* Form: reconstituted solution using matching placebo powder Route: oral or enteric Frequency: once daily Dose: daily dose adjusted for weight<br>|
| Experimental: Clopidogrel 0.2 mg/kg/day<br>0.2 mL/kg/day Clopidogrel reconstituted solution at 1mg/mL once daily. | Drug: Clopidogrel<br>* Form: reconstituted solution using Clopidogrel powder Route: oral or enteric Frequency: once daily Dose: daily dose adjusted for weight<br>* Other names: Plavix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Bleeding Events | All bleeding events experienced during the study period were collected as for any Adverse Event. The 'on-treatment' period was defined as the period from inclusion in the extension study up to 28 days after treatment discontinuation, and participants who experienced bleeding events during that period were counted. | Up to a maximum of 6 months | 
| Number of Participants According to Bleeding Type/Etiology | For all reported bleeding events, the type and the etiology of the bleeding event were collected. Participants who experienced bleeding events during the 'on-treatment period' were counted by bleeding type and etiology. | Up to a maximum of 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Shunt Thrombosis Requiring Intervention or Deaths | Outcome events, shunt thrombosis requiring intervention or death, experienced during the study period were recorded. Participants were counted excluding the events that occured after the participant's protocol study end (occurrence of shunt thrombosis, next surgical procedure for correction of the congenital heart disease, death, or 18 months of age, whichever came first). | Up to a maximum of 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cyanotic congenital heart disease, shunt palliation, thrombosis, clopidogrel