Efficacy And Safety Of Clopidogrel In Neonates /Infants With Systemic To Pulmonary Artery Shunt Palliation

Heart Defects, Congenital Clinical Trial

— CLARINET  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00396877
• Other study ID #: EFC5314
• Secondary ID: 2006-000946-38
• Status: Completed
• Phase: Phase 3
• First received: November 7, 2006
• Last updated: October 14, 2014
• Start date: November 2006
• Est. completion date: February 2010

Study information

• Verified date: October 2014
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 906
• Est. completion date: February 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 92 Days

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Congenital Abnormalities
• Heart Defects, Congenital

Intervention

Drug:
• Clopidogrel (SR25990)
Form: reconstituted solution using Clopidogrel powder Route: oral or enteric Frequency: once daily Dose: daily dose adjusted for weight
• placebo
Form: reconstituted solution using matching placebo powder Route: oral or enteric Frequency: once daily Dose: daily dose adjusted for weight

Locations

Country	Name	City	State
Argentina	Sanofi-Aventis Administrative Office	Buenos Aires
Belgium	Sanofi-Aventis Administrative Office	Diegem
Brazil	Sanofi-Aventis Administrative Office	Sao Paulo
Canada	Sanofi-Aventis Administrative Office	Laval
China	Sanofi-Aventis Administrative Office	Shangaï
Denmark	Sanofi-Aventis Administrative Office	Horsholm
Egypt	Sanofi-Aventis Administrative Office	Cairo
Finland	Sanofi-Aventis Administrative Office	Helsinki
France	Sanofi-Aventis Administrative Office	Paris
Germany	Sanofi-Aventis Administrative Office	Berlin
Hong Kong	Sanofi-Aventis Administrative Office	Causeway Bay
Hungary	Sanofi-Aventis Administrative Office	Budapest
India	Sanofi-Aventis Administrative Office	Mumbai
Israel	Sanofi-Aventis Administrative Office	Natanya
Italy	Sanofi-Aventis Administrative Office	Milano
Korea, Republic of	Sanofi-Aventis Administrative Office	Seoul
Malaysia	Sanofi-Aventis Administrative Office	Kuala Lumpur
Mexico	Sanofi-Aventis Administrative Office	Mexico
Netherlands	Sanofi-Aventis Administrative Office	Gouda
Norway	Sanofi-Aventis Administrative Office	Lysaker
Poland	Sanofi-Aventis Administrative Office	Warszawa
Portugal	Sanofi-Aventis Administrative Office	Porto Salvo
Russian Federation	Sanofi-Aventis Administrative Office	Moscow
Singapore	Sanofi-Aventis Administrative Office	Singapore
South Africa	Sanofi-Aventis Administrative Office	Midrand
Spain	Sanofi-Aventis Administrative Office	Barcelona
Sweden	Sanofi-Aventis Administrative Office	Bromma
Taiwan	Sanofi-Aventis Administrative Office	Taipei
Thailand	Sanofi-Aventis Administraive Office	Bangkok
United Kingdom	Sanofi-Aventis Admnistrative Office	Guildford Surrey
United States	Sanofi-Aventis Administrative Office	Bridgewater	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  China,  Denmark,  Egypt,  Finland,  France,  Germany,  Hong Kong,  Hungary,  India,  Israel,  Italy,  Korea, Republic of,  Malaysia,  Mexico,  Netherlands,  Norway,  Poland,  Portugal,  Russian Federation,  Singapore,  South Africa,  Spain,  Sweden,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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	Yes
Secondary	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	Yes