Platelet Dysfunction Due to Drugs
Conditions
Brief summary
The mechanistic effects of empagliflozin on platelet function profiles have not yet been ascertained.
Detailed description
Sodium GLucose Transport 2 inhibitors (SGLT2I), including empagliflozin, reduce the likelihood of hospitalization for heart failure and death in persons with type 2 diabetes, of which the mechanism has not been fully elucidated. The mechanistic effects of empagliflozin on platelet function profiles have not yet been ascertained. It remains unclear if this reduction in cardiovascular death is mediated by decreased platelet reactivity.
Interventions
DRUGSGLT2 inhibitor
Sodium-Glucose Like Transporter 2 Inhibitor
Sponsors
The University of The West Indies
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Masking description
Open-Label
Intervention model description
The study will be of a prospective, single-arm, crossover trial design over a 2-year period. Patients at the Eric Williams Medical Sciences Complex (EWMSC), Mt. Hope, Trinidad and Tobago.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. between 18 and 74 years of age, 2. have stable coronary artery disease and diabetes mellitus, already on DAPT with aspirin and clopidogrel for at least 6 months,
Exclusion criteria
1. presence of active internal bleeding or history of bleeding diathesis or clinical findings associated with an increased risk of bleeding, 2. history of ischemic or hemorrhagic stroke, transient ischemic attack, intracranial neoplasm, arteriovenous malformation, or aneurysm, 3. history of clinical and/or hemodynamic instability, 4. within 1 month of placement of a bare metal stent, 5. within 30 days of coronary artery bypass graft surgery or PCI without a stent placed, 6. planned coronary revascularization, 7. treatment with fibrin-specific fibrinolytic therapy \<24 h or non-fibrin-specific fibrinolytic therapy \<48 h, 8. use of an oral anticoagulation agent or international normalized ratio \>1.5, 9. body weight \<60 kg, 10. age \>75 years, 11. hemoglobin \<10 g/dL, 12. platelet count \<100×106/μL, 13. creatinine \>2 mg/dL, 14. hepatic enzymes \>2.5 times the upper limit of normal, 15. pregnancy and/or lactation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| P2Y12 Reaction Units | 14 days | P2Y12 Reaction Units post-Empagliflozin. Citrated blood samples are processed by CRAs and study investigators. The platelet function assay to be utilized is the VerifyNow P2Y12 (VN-P2Y12) assay (Accriva, San Diego, California). In brief, the VN-P2Y12 assay is a rapid whole blood point-of-care device that reports results as P2Y12 reaction units (PRU) and percent inhibition of platelet aggregation (%IPA). Assays will be performed as per the instructions of the manufacturer previously described. |
Countries
Trinidad and Tobago
Participant flow
Recruitment details
All participants provided written informed consent to participate in this prospective, open-label study that aimed to assess the effect of empagliflozin 25 mg once daily for 10 days. Patients were screened and enrolled between January 2020 and August 2020 at the cardiology outpatient clinic at our institution (Eric Williams Medical Sciences Complex, Trinidad and Tobago).
Pre-assignment details
No enrolled patients were excluded from the study before assignment to empagliflozin.
Participants by arm
| Arm | Count |
|---|---|
| SGLT2i Empagliflozin 25 mg per oral once daily
SGLT2 inhibitor: Sodium-Glucose Like Transporter 2 Inhibitor | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Declined | 4 |
| Overall Study | Not meeeting selection criteria | 1 |
Baseline characteristics
| Characteristic | SGLT2i |
|---|---|
| Age, Continuous | 64.2 years STANDARD_DEVIATION 1 |
| P2Y12 Reaction Units (PRU) | 187.35 P2Y12 Reaction Units (PRU) STANDARD_DEVIATION 1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 19 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Trinidad and Tobago | 100 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
P2Y12 Reaction Units
P2Y12 Reaction Units post-Empagliflozin. Citrated blood samples are processed by CRAs and study investigators. The platelet function assay to be utilized is the VerifyNow P2Y12 (VN-P2Y12) assay (Accriva, San Diego, California). In brief, the VN-P2Y12 assay is a rapid whole blood point-of-care device that reports results as P2Y12 reaction units (PRU) and percent inhibition of platelet aggregation (%IPA). Assays will be performed as per the instructions of the manufacturer previously described.
Time frame: 14 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| SGLT2i | P2Y12 Reaction Units | 187.35 P2Y12 Reaction Units |