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

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

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.

Study Overview

• Status: Completed
• Conditions: Heart Defects, Congenital
• Intervention / Treatment: Drug: placebo; Drug: Clopidogrel

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil
    • Sanofi-Aventis Administrative Office
• France
  • Paris, France
    • Sanofi-Aventis Administrative Office
• Germany
  • Berlin, Germany
    • Sanofi-Aventis Administrative Office
• Hungary
  • Budapest, Hungary
    • Sanofi-Aventis Administrative Office
• India
  • Mumbai, India
    • Sanofi-Aventis Administrative Office
• Italy
  • Milano, Italy
    • Sanofi-Aventis Administrative Office
• Malaysia
  • Kuala Lumpur, Malaysia
    • Sanofi-Aventis Administrative Office
• Mexico
  • Mexico, Mexico
    • Sanofi-Aventis Administrative Office
• Poland
  • Warszawa, Poland
    • Sanofi-Aventis Administrative Office
• Portugal
  • Porto Salvo, Portugal
    • Sanofi-Aventis Administrative Office
• Russian Federation
  • Moscow, Russian Federation
    • Sanofi-Aventis Administrative Office
• Spain
  • Barcelona, Spain
    • Sanofi-Aventis Administrative Office
• Taiwan
  • Taipei, Taiwan
    • Sanofi-Aventis Administrative Office
• United Kingdom
  • Guildford Surrey, United Kingdom
    • Sanofi-Aventis Administrative Office
• United States
  • New Jersey
    • Bridgewater, New Jersey, United States, 08807
      • Sanofi-Aventis Administrative Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 0.2 mL/kg/day matching placebo solution once daily.	Drug: placebo; Form: reconstituted solution using matching placebo powder Route: oral or enteric Frequency: once daily Dose: daily dose adjusted for weight
Experimental: Clopidogrel 0.2 mg/kg/day; 0.2 mL/kg/day Clopidogrel reconstituted solution at 1mg/mL once daily.	Drug: Clopidogrel; Form: reconstituted solution using Clopidogrel powder Route: oral or enteric Frequency: once daily Dose: daily dose adjusted for weight; Other Names: Plavix; SR25990

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Avlonitis VS, Planas S, Hayes AM, Parry A. Occlusion of modified Blalock-Taussig shunt after clopidogrel cessation. Ann Thorac Surg. 2012 Feb;93(2):656-8. doi: 10.1016/j.athoracsur.2011.07.071.

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: January 29, 2009
• First Submitted That Met QC Criteria: January 30, 2009
• First Posted (Estimate): February 2, 2009

Study Record Updates

• Last Update Posted (Estimate): August 22, 2011
• Last Update Submitted That Met QC Criteria: August 18, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: clopidogrel; thrombosis; cyanotic congenital heart disease; shunt palliation
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Cardiovascular Abnormalities; Congenital Abnormalities; Heart Defects, Congenital; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel
• Other Study ID Numbers: LTS10916; 2008-004999-53 (EudraCT Number)