Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00833703
Recruitment Status : Completed
First Posted : February 2, 2009
Results First Posted : August 16, 2011
Last Update Posted : August 22, 2011
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Heart Defects, Congenital
Interventions Drug: Clopidogrel
Drug: placebo
Enrollment 49
Recruitment Details 49 participants were enrolled between January 2009 and January 2010 in 25 sites in 15 countries (7 countries involved in CLARINET study were not selected as the delay in obtaining IRB/IEC and Health Authorities approvals would prevent recruitment and/or no patient would be recruited as the second surgery is always performed before 1 year of age).
Pre-assignment Details  
Arm/Group Title Placebo Clopidogrel 0.2 mg/kg/Day
Hide Arm/Group Description 0.2 mL/kg/day matching placebo solution once daily 0.2 mL/kg/day Clopidogrel reconstituted solution at 1mg/mL once daily
Period Title: Overall Study
Started 23 [1] 26 [1]
Treated 23 26
Completed Treatment 22 24
Completed 23 [2] 25 [2]
Not Completed 0 1
Reason Not Completed
Parent(s)/guardian(s)'s request             0             1
[1]
Included
[2]
Completed follow-up
Arm/Group Title Placebo Clopidogrel 0.2 mg/kg/Day Total
Hide Arm/Group Description 0.2 mL/kg/day matching placebo solution once daily 0.2 mL/kg/day Clopidogrel reconstituted solution at 1mg/mL once daily Total of all reporting groups
Overall Number of Baseline Participants 23 26 49
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 23 participants 26 participants 49 participants
at randomization in CLARINET study 45.2  (26.1) 33.1  (20.5) 38.8  (23.8)
at inclusion 368.1  (4.2) 368.0  (2.7) 368.0  (3.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 26 participants 49 participants
Female
10
  43.5%
14
  53.8%
24
  49.0%
Male
13
  56.5%
12
  46.2%
25
  51.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 23 participants 26 participants 49 participants
United States 0 1 1
Portugal 3 1 4
Taiwan 4 5 9
Spain 0 2 2
Russian Federation 1 0 1
United Kingdom 1 2 3
Italy 0 1 1
India 0 1 1
France 0 1 1
Hungary 2 1 3
Mexico 6 4 10
Brazil 4 2 6
Malaysia 1 1 2
Poland 1 1 2
Germany 0 3 3
Weight at inclusion  
Mean (Standard Deviation)
Unit of measure:  Kilograms (kg)
Number Analyzed 23 participants 26 participants 49 participants
7.9  (1.1) 8.1  (1.2) 8.0  (1.2)
Height at inclusion  
Mean (Standard Deviation)
Unit of measure:  Centimeters (cm)
Number Analyzed 23 participants 26 participants 49 participants
71.8  (2.8) 70.0  (10.4) 70.8  (7.8)
Type of initial shunt palliation  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 23 participants 26 participants 49 participants
Modified Blalock Taussig Shunt with Norwood 0 1 1
Modified Blalock Taussig Shunt without Norwood 18 20 38
Sano procedure with Norwood 0 0 0
Sano procedure without Norwood 1 1 2
Central shunt 1 3 4
Stent of ductus arteriosus 3 1 4
Shunt on cardiopulmonary bypass  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 23 participants 26 participants 49 participants
Yes 2 5 7
No 21 21 42
Age at shunt palliation  
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 23 participants 26 participants 49 participants
25.7  (28.7) 13.7  (12.7) 19.4  (22.3)
1.Primary Outcome
Title Number of Participants With Bleeding Events
Hide Description

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.

Time Frame Up to a maximum of 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Intent-to-treat (ITT) population that consisted of all included participants. Participants were analyzed in the treatment arm allocated at randomization into the CLARINET study.
Arm/Group Title Placebo Clopidogrel 0.2 mg/kg/Day
Hide Arm/Group Description:
0.2 mL/kg/day matching placebo solution once daily
0.2 mL/kg/day Clopidogrel reconstituted solution at 1mg/mL once daily
Overall Number of Participants Analyzed 23 26
Measure Type: Number
Unit of Measure: participants
Any bleeding event 0 2
- Serious 0 0
- Serious with an outcome of death 0 0
- Leading to permanent treatment discontinuation 0 0
2.Primary Outcome
Title Number of Participants According to Bleeding Type/Etiology
Hide 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.
Time Frame Up to a maximum of 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the same population as previously (i.e. ITT population).
Arm/Group Title Placebo Clopidogrel 0.2 mg/kg/Day
Hide Arm/Group Description:
0.2 mL/kg/day matching placebo solution once daily
0.2 mL/kg/day Clopidogrel reconstituted solution at 1mg/mL once daily
Overall Number of Participants Analyzed 23 26
Measure Type: Number
Unit of Measure: participants
Spontaneous 0 1
Puncture (vascular access site) 0 1
3.Secondary Outcome
Title Number of Participants With Shunt Thrombosis Requiring Intervention or Deaths
Hide Description

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).

Time Frame Up to a maximum of 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Intent-to-treat (ITT) population that consisted of all included participants. Participants were analyzed in the treatment arm allocated at randomization into the CLARINET study.
Arm/Group Title Placebo Clopidogrel 0.2 mg/kg/Day
Hide Arm/Group Description:
0.2 mL/kg/day matching placebo solution once daily
0.2 mL/kg/day Clopidogrel reconstituted solution at 1mg/mL once daily
Overall Number of Participants Analyzed 23 26
Measure Type: Number
Unit of Measure: participants
shunt thrombosis requiring intervention 0 0
death 1 0
Time Frame Up to a maximum of 6 months. All Adverse Events (AE) experienced during the study period were collected regardless of seriousness or relationship to the drug .
Adverse Event Reporting Description The analysis was performed on the intent-to-treat population and included all AE that developed/worsened during the 'on-treatment period' (i.e. from inclusion in the extension study up to 28 days after treatment discontinuation).
 
Arm/Group Title Placebo Clopidogrel 0.2 mg/kg/Day
Hide Arm/Group Description 0.2 mL/kg/day matching placebo solution once daily 0.2 mL/kg/day Clopidogrel reconstituted solution at 1mg/mL once daily
All-Cause Mortality
Placebo Clopidogrel 0.2 mg/kg/Day
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Clopidogrel 0.2 mg/kg/Day
Affected / at Risk (%) Affected / at Risk (%)
Total   3/23 (13.04%)   6/26 (23.08%) 
Cardiac disorders     
Low cardiac output syndrome * 1  0/23 (0.00%)  1/26 (3.85%) 
Nodal arrhythmia * 1  0/23 (0.00%)  1/26 (3.85%) 
General disorders     
Pyrexia * 1  0/23 (0.00%)  1/26 (3.85%) 
Infections and infestations     
Bronchiolitis * 1  0/23 (0.00%)  1/26 (3.85%) 
Croup infectious * 1  0/23 (0.00%)  1/26 (3.85%) 
Gastroenteritis * 1  0/23 (0.00%)  1/26 (3.85%) 
Urinary tract infection * 1  0/23 (0.00%)  1/26 (3.85%) 
Viral infection * 1  0/23 (0.00%)  1/26 (3.85%) 
Nervous system disorders     
Ischaemic stroke * 1  1/23 (4.35%)  0/26 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Diaphragmatic paralysis * 1  1/23 (4.35%)  0/26 (0.00%) 
Pulmonary artery stenosis * 1  1/23 (4.35%)  0/26 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Clopidogrel 0.2 mg/kg/Day
Affected / at Risk (%) Affected / at Risk (%)
Total   7/23 (30.43%)   17/26 (65.38%) 
Cardiac disorders     
Any cardiac disorders * 1  0/23 (0.00%)  2/26 (7.69%) 
Gastrointestinal disorders     
Any gastrointestinal disorders * 1  2/23 (8.70%)  6/26 (23.08%) 
Diarrhoea * 1  1/23 (4.35%)  3/26 (11.54%) 
General disorders     
Any general disorders and administration site conditions * 1  1/23 (4.35%)  6/26 (23.08%) 
Pyrexia * 1  0/23 (0.00%)  4/26 (15.38%) 
Infections and infestations     
Any infections and infestations * 1  6/23 (26.09%)  14/26 (53.85%) 
Upper respiratory tract infection * 1  0/23 (0.00%)  6/26 (23.08%) 
Gastroenteritis * 1  2/23 (8.70%)  2/26 (7.69%) 
Ear infection * 1  0/23 (0.00%)  2/26 (7.69%) 
Lower respiratory tract infection * 1  0/23 (0.00%)  2/26 (7.69%) 
Viral infection * 1  0/23 (0.00%)  2/26 (7.69%) 
Pharyngitis * 1  3/23 (13.04%)  1/26 (3.85%) 
Nasopharyngitis * 1  2/23 (8.70%)  1/26 (3.85%) 
Injury, poisoning and procedural complications     
Any injury, poisoning and procedural complications * 1  1/23 (4.35%)  3/26 (11.54%) 
Respiratory, thoracic and mediastinal disorders     
Any respiratory, thoracic and mediastinal disorders * 1  1/23 (4.35%)  4/26 (15.38%) 
Cough * 1  0/23 (0.00%)  3/26 (11.54%) 
Skin and subcutaneous tissue disorders     
Any skin and subcutaneous tissue disorders * 1  1/23 (4.35%)  2/26 (7.69%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If no publication has occurred within 12 months after trial completion, the Investigator can publish the results. Prior to publication, the sponsor shall review the manuscript and can request changes, provided they do not jeopardize the accuracy and/or the scientific value of the publication. The approval is given in writing by the sponsor, not exceeding 90 days.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Trial Transparency Team
Organization: sanofi-aventis
EMail: Contact_US@sanofi-aventis.com
Layout table for additonal information
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00833703     History of Changes
Other Study ID Numbers: LTS10916
2008-004999-53 ( EudraCT Number )
First Submitted: January 29, 2009
First Posted: February 2, 2009
Results First Submitted: July 20, 2011
Results First Posted: August 16, 2011
Last Update Posted: August 22, 2011