DECADES: A Study to Evaluate the Discontinuation Effect of Clopidogrel After Drug Eluting Stent Implantation in Non-diabetic Patients

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00493779
• Collaborator: Sanofi (Industry)
• Enrollment: 103
• Locations: 6
• Arm: 1
• Duration (Months): 8
• Patients Per Site: 17.2
• Patients Per Site Per Month: 2.1

Study Details

Study Description

Brief Summary

The purpose of the study is to look at the biomarkers of inflammation and platelet activation in patients with drug eluting stents implanted approximately 12 months ago on aspirin and statin, for a 4-week period after the routine discontinuation of clopidogrel

Condition or Disease	Intervention/Treatment	Phase
Antiplatelet Aggregation	Procedure: Blood Collection	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 103 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Official Title: An Exploratory, Multi-Center, Open-Label, Single-Arm Study to Evaluate the Discontinuation Effect of Clopidogrel After Drug Eluting Stent (DECADES) on Inflammatory and Platelet Activation Markers in Subjects Who Are Receiving Low Dose Acetylsalicylic Acid (ASA)
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Jun 1, 2008
• Actual Study Completion Date: Jun 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: 1 Effect of Clopidogrel withdrawal on biomarkers will be assessed via blood draws	Procedure: Blood Collection; 4 weeks

Outcome Measures

Primary Outcome Measures

1. Adjusted Mean Percent Changes From Baseline in Soluble CD40 Ligand (sCD40L) [Week 1, Week 2, Week 3, Week 4 (primary timepoint)]

   Based on ANCOVA models performed on log scale controlling for site & natural logarithm of baseline soluble CD40 Ligand value. Percent changes from baseline can be interpreted as the difference of biomarker timepoint value minus baseline value divided by baseline value. Positive percent change might indicate possible enhanced platelet activation.

Secondary Outcome Measures

1. Adjusted Mean Percent Changes From Baseline in Plasma Soluble P-Selectin [Week 1, Week 2, Week 3, Week 4]

   Based on ANCOVA models performed on log scale controlling for site and natural logarithm of baseline Plasma Soluble P-selectin value. Percent changes from baseline can be interpreted as difference of biomarker timepoint value minus baseline value divided by baseline value. Positive percent change is known to be mediated by increases in sCD40L.

2. Adjusted Mean Percent Changes From Baseline in Hs-CRP [Week 1, Week 2, Week 3, Week 4]

   ANCOVA models performed on log scale controlling for site & natural logarithm of baseline hs-CRP. Back-transformed mean percent changes are presented. Percent changes from baseline can be interpreted as difference of biomarker timepoint value - baseline value ÷ baseline value. Since there is no measure of platelet inhibition or overall thrombogenicity assay presented here, a negative percent change for this measure can not be judged on its own as indicating improvement.

3. Adverse Events (AE) / Serious Adverse Events (SAE)Deaths, and AEs Leading to Discontinuation of Follow-up [Throughout 4-week follow-up period]

   An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a patient or clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects with one or more drug-eluting stents of any type who are coming to the end of their 12 months of clopidogrel (75 mg daily) treatment

• Subjects receiving low dose ASA

• Subjects receiving a statin

• Current medication regimen (including ASA and statins) must have been stable for three (3) months. i.e. no initiation of new prescription medication or change in dosage of any previously initiated medication within three (3) months of entering this study

• Subjects with no clinical history of diabetes mellitis

• Men and women, ages 18 years or older

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Local Institution	Paris		France	75013
2	Local Institution	Mainz		Germany	55101
3	Local Institution	Nieuwegein		Netherlands	3435 CM
4	Local Institution	Rotterdam		Netherlands	3015 GD
5	Local Institution	Glasgow	Central	United Kingdom	G11 6NT
6	Local Institution	Southampton	Hampshire	United Kingdom	SO16 6YD

Sponsors and Collaborators

• Bristol-Myers Squibb
• Sanofi

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

• Wykrzykowska JJ, Warnholtz A, de Jaeger P, Curzen N, Oldroyd KG, Collet JP, Ten Berg JM, Rademaker T, Goedhart D, Lissens J, Kint PP, Serruys PW. Effect of clopidogrel discontinuation at 1 year after drug eluting stent placement on soluble CD40L, P-selectin and C-reactive protein levels: DECADES (Discontinuation Effect of Clopidogrel After Drug Eluting Stent): a multicenter, open-label study. J Thromb Thrombolysis. 2009 Nov;28(4):410-7. doi: 10.1007/s11239-009-0354-y.

• ClinicalTrials.gov Identifier: NCT00493779
• Other Study ID Numbers: CV149-208; Eudract number: 2007-000713-11
• First Posted: Jun 28, 2007
• Last Update Posted: Aug 10, 2010
• Last Verified: Jun 1, 2010

Study Results

Participant Flow

Pre-assignment Detail	103 subjects who were enrolled and treated with clopidogrel, were enrolled, of which 98 subjects had discontinued clopidogrel treatment and entered follow-up phase (study phase).

Arm/Group Title	Clopidogrel Withdrawal Population
Arm/Group Description	All enrolled participants in whom clopidogrel treatment was discontinued.
Period Title: Overall Study
STARTED	98
COMPLETED	97
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Clopidogrel Withdrawal Population
Arm/Group Description	All enrolled participants in whom clopidogrel treatment was discontinued.
Overall Participants	98
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.3 (8.5)
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63
Sex: Female, Male (Count of Participants)
Female	20 20.4%
Male	78 79.6%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	93 94.9%
Asian Oriental	5 5.1%
Mean Baseline High Sensitivity C-Reactive Protein (hs-CRP) (mg/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/L]	1.70 (2.052)
Mean Baseline Plasma Soluble P-Selectin (ng/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/mL]	44.59 (14.898)
Mean Baseline Soluble CD40 Ligand (ng/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/L]	223.76 (186.513)

Outcome Measures

1. Secondary Outcome

Title	Adjusted Mean Percent Changes From Baseline in Plasma Soluble P-Selectin
Description	Based on ANCOVA models performed on log scale controlling for site and natural logarithm of baseline Plasma Soluble P-selectin value. Percent changes from baseline can be interpreted as difference of biomarker timepoint value minus baseline value divided by baseline value. Positive percent change is known to be mediated by increases in sCD40L.
Time Frame	Week 1, Week 2, Week 3, Week 4

Outcome Measure Data

Analysis Population Description

Number of patients in the biomarker analysis population having baseline Plasma Soluble P-selectin value (n=95) and at least one post-clopidogrel withdrawal measurement for Plasma Soluble P-selectin value. No imputation technique for missing values was applied.

Arm/Group Title	Biomarker Analysis Population
Arm/Group Description	All participants in the Clopidogrel Withdrawal Population having a baseline and at least one post clopidogrel withdrawal measurement for any of the 3 biomarkers collected.
Measure Participants	95
Baseline Value (units=ng/mL) (n=95)	44.59 (1.53)
Mean Percent Change from Baseline at Week 1 (n=92)	9.00 (2.38)
Mean Percent Change from Baseline at Week 2 (n=91)	11.10 (2.11)
Mean Percent Change from Baseline at Week 3 (n=91)	3.63 (2.69)
Mean Percent Change from Baseline at Week 4 (n=89)	1.90 (2.76)

2. Primary Outcome

Title	Adjusted Mean Percent Changes From Baseline in Soluble CD40 Ligand (sCD40L)
Description	Based on ANCOVA models performed on log scale controlling for site & natural logarithm of baseline soluble CD40 Ligand value. Percent changes from baseline can be interpreted as the difference of biomarker timepoint value minus baseline value divided by baseline value. Positive percent change might indicate possible enhanced platelet activation.
Time Frame	Week 1, Week 2, Week 3, Week 4 (primary timepoint)

Outcome Measure Data

Analysis Population Description

Number of participants in the biomarker analysis population having a baseline soluble CD40 Ligand value (n=95) and at least one post-clopidogrel withdrawal measurement for soluble CD40 Ligand value. No imputation technique for missing values was applied.

Arm/Group Title	Biomarker Analysis Population
Arm/Group Description	All participants in the Clopidogrel Withdrawal Population having a baseline and at least one post clopidogrel withdrawal measurement for any of the 3 biomarkers collected.
Measure Participants	95
Baseline value (units=ng/L) (n=95)	223.76 (19.14)
Mean Percent Change from Baseline at Week 1 (n=92)	35.04 (10.37)
Mean Percent Change from Baseline at Week 2 (n=91)	38.88 (10.76)
Mean Percent Change from Baseline at Week 3 (n=91)	32.74 (9.68)
Mean Percent Change from Baseline at Week 4 (n=89)	39.42 (11.07)

3. Secondary Outcome

Title	Adjusted Mean Percent Changes From Baseline in Hs-CRP
Description	ANCOVA models performed on log scale controlling for site & natural logarithm of baseline hs-CRP. Back-transformed mean percent changes are presented. Percent changes from baseline can be interpreted as difference of biomarker timepoint value - baseline value ÷ baseline value. Since there is no measure of platelet inhibition or overall thrombogenicity assay presented here, a negative percent change for this measure can not be judged on its own as indicating improvement.
Time Frame	Week 1, Week 2, Week 3, Week 4

Outcome Measure Data

Analysis Population Description

Number of patients in the biomarker analysis population having baseline hs-CRP value and at least one post clopidogrel withdrawal measurement for hs-CRP value. No imputation technique for missing values was applied.

Arm/Group Title	Biomarker Analysis Population
Arm/Group Description	All participants in the Clopidogrel Withdrawal Population having a baseline and at least one post clopidogrel withdrawal measurement for any of the 3 biomarkers collected.
Measure Participants	98
Baseline Value (units=mg/L) (n=98)	1.70 (0.21)
Mean Percent Change from Baseline at Week 1 (n=97)	-20.59 (6.76)
Mean Percent Change from Baseline at Week 2 (n=95)	-22.89 (6.78)
Mean Percent Change from Baseline at Week 3 (n=96)	-19.32 (8.22)
Mean Percent Change from Baseline at Week 4 (n=96)	-17.70 (8.48)

4. Secondary Outcome

Title	Adverse Events (AE) / Serious Adverse Events (SAE)Deaths, and AEs Leading to Discontinuation of Follow-up
Description	An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a patient or clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
Time Frame	Throughout 4-week follow-up period

Outcome Measure Data

Analysis Population Description

All enrolled patients in whom clopidogrel treatment was discontinued.

Arm/Group Title	Clopidogrel Withdrawal Population
Arm/Group Description	All enrolled participants in whom clopidogrel treatment was discontinued.
Measure Participants	98
Deaths	0 0%
Any AE	20 20.4%
AEs leading up to Discontinuation	0 0%
SAEs	2 2%

Adverse Events

Arm/Group Title	Clopidogrel Withdrawal Population
Arm/Group Description	All enrolled participants in whom clopidogrel treatment was discontinued.
All Cause Mortality
	Clopidogrel Withdrawal Population
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Clopidogrel Withdrawal Population
	Affected / at Risk (%)	# Events
Total	2/98 (2%)
Cardiac disorders
Angina unstable	1/98 (1%)
General disorders
Non-cardiac chest pain	1/98 (1%)
Other (Not Including Serious) Adverse Events
	Clopidogrel Withdrawal Population
	Affected / at Risk (%)	# Events
Total	0/98 (0%)

Limitations/Caveats

The open-label and exploratory nature of this small study and the absence of control group inherently limit the interpretability of the results.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.