Efficacy And 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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Contemporary management of cyanotic congenital heart disease includes three stages of surgery. Incidence of shunt thrombosis and death between the two first stages of palliation remains important. The primary objective of the study is to evaluate the efficacy of Clopidogrel 0.2 mg/kg/day for the reduction of all cause mortality and shunt related morbidity in neonates or infants with cyanotic congenital heart disease palliated with a systemic-to-pulmonary artery shunt (e.g. modified Blalock Taussig Shunt [BTS]). The secondary objective was to assess the safety of Clopidogrel in the study population.

Detailed Description
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In this event-driven study, participants were to be randomized and treated as soon as possible after shunt placement. They were then to be treated and followed until the primary endpoint criteria was reached i.e. (shunt thrombosis, the next surgical procedure for correction of the congenital heart disease or death) or one year of age or the common study-end-date, which ever came first. The common study-en-date was defined as the date when it was projected that 172 participants would have reached the primary endpoint criteria.

Official Title
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International Randomized Double Blind Study Evaluating the Efficacy and the Safety of Clopidogrel 0.2 mg/kg Once Daily Versus Placebo in Neonates and Infants With Cyanotic Congenital Heart Disease Palliated With Systemic to Pulmonary Artery Shunt

Conditions
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Heart Defects, Congenital

Intervention / Treatment
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* Drug: Clopidogrel (SR25990)
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cyanotic congenital heart disease treated by any palliative systemic-to-pulmonary artery shunt. Exclusion Criteria: Active bleeding or increase risk of bleeding, Allergy to 2 or more classes of drug, Unable to receive drug orally or enterically, Current clinically significant or persistent thrombocytopenia, neutropenia, severe hepatic or renal failure.

Ages Eligible for Study
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Maximum Age: 92 Days

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | 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> | Drug: Clopidogrel (SR25990)<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 Reaching Primary Endpoint Criteria (First Occurrence of Death / Shunt Thrombosis / Cardiac Procedure < 120 Days Considered of Thrombotic Nature) | The primary endpoint was the first occurence of any of the following events: Death (including heart transplant); Shunt thrombosis requiring intervention; Hospitalization for bi-directional Glenn procedure or any cardiac related intervention prior to 120 days of age following an event or a shunt narrowing considered to be of thrombotic nature by the blinded adjudication committee. Only the first event was counted. | Median follow-up of 5.8 months (up to a maximum of 12 months after randomization) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Bleeding Events | Bleeding events spanning from signature of the Informed Consent Form up to the last visit were collected as for any Adverse Event. The 'on-treatment' period was defined as the period from randomization up until 28 days after treatment discontinuation or final follow-up visit, whichever came first, and participants who experienced bleeding events during that period were counted. | From randomization up to 28 days after treatment discontinuation or final follow-up visit, whichever comes first | 
| 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. Participants who had multiple bleedings could be counted several times. | From randomization up to 28 days after treatment discontinuation or final follow-up visit, whichever comes first | 

 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