Antiplatelet Aggregation
Conditions
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
Interventions
PROCEDUREBlood Collection
4 weeks
Sponsors
Sanofi
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
France, Germany, Netherlands, United Kingdom
Participant flow
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| Clopidogrel Withdrawal Population All enrolled participants in whom clopidogrel treatment was discontinued. | 98 |
| Total | 98 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Logistical issue at site | 1 |
Baseline characteristics
| Characteristic | Clopidogrel Withdrawal Population |
|---|---|
| Age Continuous | 63.3 years STANDARD_DEVIATION 8.5 |
| Mean Baseline High Sensitivity C-Reactive Protein (hs-CRP) | 1.70 mg/L STANDARD_DEVIATION 2.052 |
| Mean Baseline Plasma Soluble P-Selectin | 44.59 ng/mL STANDARD_DEVIATION 14.898 |
| Mean Baseline Soluble CD40 Ligand | 223.76 ng/L STANDARD_DEVIATION 186.513 |
| Race/Ethnicity, Customized Asian Oriental | 5 participants |
| Race/Ethnicity, Customized Caucasian | 93 participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 98 |
| serious Total, serious adverse events | 2 / 98 |
Outcome results
Primary
Adjusted Mean Percent Changes From Baseline in Soluble CD40 Ligand (sCD40L)
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Biomarker Analysis Population | Adjusted Mean Percent Changes From Baseline in Soluble CD40 Ligand (sCD40L) | Baseline value (units=ng/L) (n=95) | 223.76 percent change | Standard Error 19.14 |
| Biomarker Analysis Population | Adjusted Mean Percent Changes From Baseline in Soluble CD40 Ligand (sCD40L) | Mean Percent Change from Baseline at Week 1 (n=92) | 35.04 percent change | Standard Error 10.37 |
| Biomarker Analysis Population | Adjusted Mean Percent Changes From Baseline in Soluble CD40 Ligand (sCD40L) | Mean Percent Change from Baseline at Week 2 (n=91) | 38.88 percent change | Standard Error 10.76 |
| Biomarker Analysis Population | Adjusted Mean Percent Changes From Baseline in Soluble CD40 Ligand (sCD40L) | Mean Percent Change from Baseline at Week 3 (n=91) | 32.74 percent change | Standard Error 9.68 |
| Biomarker Analysis Population | Adjusted Mean Percent Changes From Baseline in Soluble CD40 Ligand (sCD40L) | Mean Percent Change from Baseline at Week 4 (n=89) | 39.42 percent change | Standard Error 11.07 |
Secondary
Adjusted Mean Percent Changes From Baseline in Hs-CRP
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Biomarker Analysis Population | Adjusted Mean Percent Changes From Baseline in Hs-CRP | Baseline Value (units=mg/L) (n=98) | 1.70 percent change | Standard Error 0.21 |
| Biomarker Analysis Population | Adjusted Mean Percent Changes From Baseline in Hs-CRP | Mean Percent Change from Baseline at Week 1 (n=97) | -20.59 percent change | Standard Error 6.76 |
| Biomarker Analysis Population | Adjusted Mean Percent Changes From Baseline in Hs-CRP | Mean Percent Change from Baseline at Week 2 (n=95) | -22.89 percent change | Standard Error 6.78 |
| Biomarker Analysis Population | Adjusted Mean Percent Changes From Baseline in Hs-CRP | Mean Percent Change from Baseline at Week 3 (n=96) | -19.32 percent change | Standard Error 8.22 |
| Biomarker Analysis Population | Adjusted Mean Percent Changes From Baseline in Hs-CRP | Mean Percent Change from Baseline at Week 4 (n=96) | -17.70 percent change | Standard Error 8.48 |
Secondary
Adjusted Mean Percent Changes From Baseline in Plasma Soluble P-Selectin
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Biomarker Analysis Population | Adjusted Mean Percent Changes From Baseline in Plasma Soluble P-Selectin | Baseline Value (units=ng/mL) (n=95) | 44.59 percent change | Standard Error 1.53 |
| Biomarker Analysis Population | Adjusted Mean Percent Changes From Baseline in Plasma Soluble P-Selectin | Mean Percent Change from Baseline at Week 1 (n=92) | 9.00 percent change | Standard Error 2.38 |
| Biomarker Analysis Population | Adjusted Mean Percent Changes From Baseline in Plasma Soluble P-Selectin | Mean Percent Change from Baseline at Week 2 (n=91) | 11.10 percent change | Standard Error 2.11 |
| Biomarker Analysis Population | Adjusted Mean Percent Changes From Baseline in Plasma Soluble P-Selectin | Mean Percent Change from Baseline at Week 3 (n=91) | 3.63 percent change | Standard Error 2.69 |
| Biomarker Analysis Population | Adjusted Mean Percent Changes From Baseline in Plasma Soluble P-Selectin | Mean Percent Change from Baseline at Week 4 (n=89) | 1.90 percent change | Standard Error 2.76 |
Secondary
Adverse Events (AE) / Serious Adverse Events (SAE)Deaths, and AEs Leading to Discontinuation of Follow-up
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
Population: All enrolled patients in whom clopidogrel treatment was discontinued.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Biomarker Analysis Population | Adverse Events (AE) / Serious Adverse Events (SAE)Deaths, and AEs Leading to Discontinuation of Follow-up | Deaths | 0 Participants |
| Biomarker Analysis Population | Adverse Events (AE) / Serious Adverse Events (SAE)Deaths, and AEs Leading to Discontinuation of Follow-up | Any AE | 20 Participants |
| Biomarker Analysis Population | Adverse Events (AE) / Serious Adverse Events (SAE)Deaths, and AEs Leading to Discontinuation of Follow-up | AEs leading up to Discontinuation | 0 Participants |
| Biomarker Analysis Population | Adverse Events (AE) / Serious Adverse Events (SAE)Deaths, and AEs Leading to Discontinuation of Follow-up | SAEs | 2 Participants |