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

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

This study has been completed.

Study NCT00396877 Information provided by Sanofi-Aventis

First Received on November 7, 2006. Last Updated on March 24, 2011 History of Changes

Results First Received: February 15, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition:	Heart Defects, Congenital
Interventions:	Drug: Clopidogrel (SR25990) Drug: placebo

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Recruitment was initially planned with a minimum of 490 participants anticipating that it would continue until a total of 172 participants reaching primary endpoint criteria is achieved. Finally 906 participants were enrolled and randomized between November 2006 and October 2009 in 134 sites in 31 countries. Actual median follow-up was 5.8 months.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A participant was considered randomized when informed consent had been obtained and there was confirmation of successful allocation of a randomization number through the study treatment allocation system (Interactive Voice Response System).

Reporting Groups

	Description
Placebo	Reconstituted solution using Clopidogrel matching placebo powder administered once daily with a graduated syringe in the mouth or via a feeding tube.
Clopidogrel 0.2 mg/kg/Day	Reconstituted solution using Clopidogrel powder administered once daily with a graduated syringe in the mouth or via a feeding tube. Route: oral or enteric Frequency: once daily Dose: daily dose adjusted for weight

Description

Placebo

Reconstituted solution using Clopidogrel matching placebo powder administered once daily with a graduated syringe in the mouth or via a feeding tube.

Clopidogrel 0.2 mg/kg/Day

Reconstituted solution using Clopidogrel powder administered once daily with a graduated syringe in the mouth or via a feeding tube.

Route: oral or enteric

Frequency: once daily

Dose: daily dose adjusted for weight

Participant Flow: Overall Study

	Placebo	Clopidogrel 0.2 mg/kg/Day
STARTED	439 ^[1]	467 ^[1]
Treated	436	464
Completed Treatment	356	352
COMPLETED	433 ^[2]	459 ^[2]
NOT COMPLETED	6	8
Lost to Follow-up	2	1
Parent(s)/guardian(s)'s request	4	7

[1]	Randomized
[2]	Completed follow-up

Baseline Characteristics

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Reporting Groups

	Description
Placebo	No text entered.
Clopidogrel 0.2 mg/kg/Day	No text entered.

Baseline Measures

	Placebo	Clopidogrel 0.2 mg/kg/Day	Total
Number of Participants [units: participants]	439	467	906
Age [units: days] Mean ± Standard Deviation	36.0 ± 22.5	36.1 ± 22.3	36.1 ± 22.4
Age, Customized [units: participants]
≤ 30 days	223	238	461
30 (<) - 92 days	216	229	445
Gender [units: participants]
Female	185	198	383
Male	254	269	523
Region of Enrollment [units: participants]
United States	90	88	178
Portugal	10	10	20
Taiwan	12	10	22
Hong Kong	1	0	1
Thailand	2	3	5
Spain	16	14	30
Israel	3	4	7
Russian Federation	13	15	28
Italy	20	19	39
India	20	27	47
France	11	10	21
Malaysia	5	4	9
Denmark	3	3	6
South Africa	13	13	26
Netherlands	2	4	6
China	10	11	21
Korea, Republic of	3	2	5
Finland	2	1	3
United Kingdom	16	16	32
Egypt	4	6	10
Hungary	9	9	18
Mexico	32	37	69
Canada	5	6	11
Argentina	24	28	52
Brazil	31	34	65
Belgium	9	12	21
Poland	3	7	10
Singapore	2	2	4
Germany	54	59	113
Norway	8	8	16
Sweden	6	5	11
Weight [units: kilograms (kg)] Mean ± Standard Deviation	3.5 ± 0.7	3.4 ± 0.7	3.5 ± 0.7
Height [units: Centimeters (cm)] Mean ± Standard Deviation	51.8 ± 4.6	51.4 ± 4.4	51.6 ± 4.5
Type of systemic-to-pulmonary artery shunt palliation ^[1] [units: participants]
Modified Blalock Taussig Shunt with Norwood	51	62	113
Modified Blalock Taussig Shunt without Norwood	252	257	509
Sano procedure with Norwood	54	60	114
Sano procedure without Norwood	2	5	7
Central shunt	38	40	78
Stent of ductus arteriosus	42	42	84
Not applicable	0	1	1
Shunt on cardiopulmonary bypass [units: participants]
Yes	177	194	371
No	262	273	535
Age at shunt palliation [units: days] Mean ± Standard Deviation	16.0 ± 18.7	16.2 ± 18.6	16.1 ± 18.7
Time from shunt palliation to randomization [units: participants]
≤ 1 week	116	113	229
1 (<) to 2 weeks	105	126	231
2 (<) to 4 weeks	117	119	236
> 4 weeks	101	109	210

[1]	One participant didn't have a systemic-to-pulmonary artery shunt but underwent stenting of the right ventricular outflow track.

Outcome Measures

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1. Primary:

Number of Participants Reaching Primary Endpoint Criteria (First Occurrence of Death / Shunt Thrombosis / Cardiac Procedure < 120 Days Considered of Thrombotic Nature) [ Time Frame: Median follow-up of 5.8 months (up to a maximum of 12 months after randomization) ]

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2. Secondary:

Number of Participants With Bleeding Events [ Time Frame: From randomization up to 28 days after treatment discontinuation or final follow-up visit, whichever comes first ]

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3. Secondary:

Number of Participants According to Bleeding Type/Etiology [ Time Frame: From randomization up to 28 days after treatment discontinuation or final follow-up visit, whichever comes first ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Trial Transparency Team
Organization: sanofi-aventis
e-mail: Contact-US@sanofi-aventis.com

No publications provided

Responsible Party:	International Clinical Development Study Director, sanofi-aventis
ClinicalTrials.gov Identifier:	NCT00396877 History of Changes
Other Study ID Numbers:	EFC5314, 2006-000946-38
Study First Received:	November 7, 2006
Results First Received:	February 15, 2011
Last Updated:	March 24, 2011
Health Authority:	United States: Food and Drug Administration