Efficacy And Safety Of Clopidogrel In Neonates /Infants With Systemic To Pulmonary Artery Shunt Palliation (CLARINET)
Primary Purpose
Heart Defects, Congenital
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Clopidogrel (SR25990)
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Heart Defects, Congenital focused on measuring cyanotic congenital heart disease, shunt palliation, thrombosis, clopidogrel
Eligibility Criteria
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.
Sites / Locations
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administraive Office
- Sanofi-Aventis Admnistrative Office
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
Clopidogrel 0.2 mg/kg/day
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Full Information
NCT ID
NCT00396877
First Posted
November 7, 2006
Last Updated
October 14, 2014
Sponsor
Sanofi
Collaborators
Bristol-Myers Squibb
1. Study Identification
Unique Protocol Identification Number
NCT00396877
Brief Title
Efficacy And Safety Of Clopidogrel In Neonates /Infants With Systemic To Pulmonary Artery Shunt Palliation
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2014
Overall Recruitment Status
Completed
Study Start Date
November 2006 (undefined)
Primary Completion Date
February 2010 (Actual)
Study Completion Date
February 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
Collaborators
Bristol-Myers Squibb
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Defects, Congenital
Keywords
cyanotic congenital heart disease, shunt palliation, thrombosis, clopidogrel
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
906 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
Clopidogrel 0.2 mg/kg/day
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Clopidogrel (SR25990)
Other Intervention Name(s)
Plavix
Intervention Description
Form: reconstituted solution using Clopidogrel powder
Route: oral or enteric
Frequency: once daily
Dose: daily dose adjusted for weight
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
Form: reconstituted solution using matching placebo powder
Route: oral or enteric
Frequency: once daily
Dose: daily dose adjusted for weight
Primary Outcome Measure Information:
Title
Number of Participants Reaching Primary Endpoint Criteria (First Occurrence of Death / Shunt Thrombosis / Cardiac Procedure < 120 Days Considered of Thrombotic Nature)
Description
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.
Time Frame
Median follow-up of 5.8 months (up to a maximum of 12 months after randomization)
Secondary Outcome Measure Information:
Title
Number of Participants With Bleeding Events
Description
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.
Time Frame
From randomization up to 28 days after treatment discontinuation or final follow-up visit, whichever comes first
Title
Number of Participants According to Bleeding Type/Etiology
Description
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.
Time Frame
From randomization up to 28 days after treatment discontinuation or final follow-up visit, whichever comes first
10. Eligibility
Sex
All
Maximum Age & Unit of Time
92 Days
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
International Clinical Development Clinical Study Director
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Sanofi-Aventis Administrative Office
City
Bridgewater
State/Province
New Jersey
ZIP/Postal Code
94609
Country
United States
Facility Name
Sanofi-Aventis Administrative Office
City
Buenos Aires
Country
Argentina
Facility Name
Sanofi-Aventis Administrative Office
City
Diegem
Country
Belgium
Facility Name
Sanofi-Aventis Administrative Office
City
Sao Paulo
Country
Brazil
Facility Name
Sanofi-Aventis Administrative Office
City
Laval
Country
Canada
Facility Name
Sanofi-Aventis Administrative Office
City
Shangaï
Country
China
Facility Name
Sanofi-Aventis Administrative Office
City
Horsholm
Country
Denmark
Facility Name
Sanofi-Aventis Administrative Office
City
Cairo
Country
Egypt
Facility Name
Sanofi-Aventis Administrative Office
City
Helsinki
Country
Finland
Facility Name
Sanofi-Aventis Administrative Office
City
Paris
Country
France
Facility Name
Sanofi-Aventis Administrative Office
City
Berlin
Country
Germany
Facility Name
Sanofi-Aventis Administrative Office
City
Causeway Bay
Country
Hong Kong
Facility Name
Sanofi-Aventis Administrative Office
City
Budapest
Country
Hungary
Facility Name
Sanofi-Aventis Administrative Office
City
Mumbai
Country
India
Facility Name
Sanofi-Aventis Administrative Office
City
Natanya
Country
Israel
Facility Name
Sanofi-Aventis Administrative Office
City
Milano
Country
Italy
Facility Name
Sanofi-Aventis Administrative Office
City
Seoul
Country
Korea, Republic of
Facility Name
Sanofi-Aventis Administrative Office
City
Kuala Lumpur
Country
Malaysia
Facility Name
Sanofi-Aventis Administrative Office
City
Mexico
Country
Mexico
Facility Name
Sanofi-Aventis Administrative Office
City
Gouda
Country
Netherlands
Facility Name
Sanofi-Aventis Administrative Office
City
Lysaker
Country
Norway
Facility Name
Sanofi-Aventis Administrative Office
City
Warszawa
Country
Poland
Facility Name
Sanofi-Aventis Administrative Office
City
Porto Salvo
Country
Portugal
Facility Name
Sanofi-Aventis Administrative Office
City
Moscow
Country
Russian Federation
Facility Name
Sanofi-Aventis Administrative Office
City
Singapore
Country
Singapore
Facility Name
Sanofi-Aventis Administrative Office
City
Midrand
Country
South Africa
Facility Name
Sanofi-Aventis Administrative Office
City
Barcelona
Country
Spain
Facility Name
Sanofi-Aventis Administrative Office
City
Bromma
Country
Sweden
Facility Name
Sanofi-Aventis Administrative Office
City
Taipei
Country
Taiwan
Facility Name
Sanofi-Aventis Administraive Office
City
Bangkok
Country
Thailand
Facility Name
Sanofi-Aventis Admnistrative Office
City
Guildford Surrey
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
23782178
Citation
Wessel DL, Berger F, Li JS, Dahnert I, Rakhit A, Fontecave S, Newburger JW; CLARINET Investigators. Clopidogrel in infants with systemic-to-pulmonary-artery shunts. N Engl J Med. 2013 Jun 20;368(25):2377-84. doi: 10.1056/NEJMoa1114588.
Results Reference
derived
Learn more about this trial
Efficacy And Safety Of Clopidogrel In Neonates /Infants With Systemic To Pulmonary Artery Shunt Palliation
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