Diabetes Mellitus, Type 2, Dyslipidemia Associated With Type II Diabetes Mellitus, Percutaneous Coronary Intervention
Conditions
Brief summary
Prospective, single center, double-blind, randomized pharmacodynamic experimental study. The study will enroll 150 subjects with ASCVD on optimal statin therapy as per physician and Diabetes Mellitus (DM) undergoing elective Percutaneous Coronary Intervention (PCI). Eligible patients will be randomized for 30 day treatment to either 1) evolocumab 420 mg ; or 2) placebo.
Detailed description
This is a double-blind randomized clinical trial of evolocumab versus placebo in patients with ASCVD and DM on clopidogrel and aspirin undergoing PCI. The study is aimed to assess 1. the effect of evolocumab therapy on platelet activation and reactivity; 2. the effect of evolocumab on biomarkers of platelet activation and inflammation. Eligible patients will be randomized prior to start the PCI equally to either: 1. 420 mg evolocumab ; or 2. placebo. The randomized treatment will be administered in subcutaneous injections. The laboratory assessments will be performed before (baseline), and 16-24 hours and 30-days after randomization. Subject participation will be 30 days from the randomization.
Interventions
DRUGEvolocumab
Patients will receive evolocumab 420 mg administered subcutaneously
DRUGPlacebo
Patients will receive placebo administered subcutaneously
Sponsors
Inova Health Care Services
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Diabetes Mellitus * Dyslipidemia * Undergoing elective PCI
Exclusion criteria
* Patients with recent Acute Coronary Syndrome (≤1 month) * Patients on dual antiplatelet treatment (DAPT) with ticagrelor or prasugrel * Patients undergoing urgent/emergent PCI for stent thrombosis * Severe acute or chronic medical or psychiatric condition * Pregnancy * Participation in another experimental clinical trial, without formal approval * Unwillingness or inability to comply with the requirements of this protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Adenosine Diphosphate (ADP) Stimulated P-selectin Expression | Baseline and after 30 days of treatment | Change from baseline in ADP-stimulated P-selectin expression (% Positive Cells) as measured by flow cytometry between treatment groups (420 mg evolocumab treatment and placebo). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in ADP-unstimulated P-selectin Expression | Baseline and after 30 days of treatment | Change in ADP-unstimulated P-selectin expression (% Positive Cells) between treatment groups (420 mg evolocumab treatment and placebo) |
| Change in ADP-stimulated Lectin-like oxLDL [Oxidized Low-density Lipoprotein] Receptor-1 Mean Fluorescence Intensity (MFI) | Baseline and after 30 days of treatment | Change in ADP-stimulated LOX-1 (MFI) as measured by flow cytometry between treatment groups (420 mg evolocumab treatment and placebo) |
| Change in ADP-stimulated Cluster of Differentiation (CD)-147 MFI | Baseline and after 30 days of treatment | Change in ADP-stimulated CD-147 mean fluorescence intensity (MFI) as measured by flow cytometry between treatment groups (420 mg evolocumab treatment and placebo) |
Countries
United States
Participant flow
Pre-assignment details
A total of 31 participants were screened, 4 met eligibility and were randomized to the study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Evolocumab 420mg Participants on optimal statin therapy undergoing elective PCI will receive evolocumab 420mg.
Evolocumab: Participants will receive evolocumab 420 mg administered subcutaneously | 3 |
| Placebo Participants on optimal statin therapy undergoing elective PCI will receive placebo
Placebo: Participants will receive placebo administered subcutaneously | 1 |
| Total | 4 |
Baseline characteristics
| Characteristic | Evolocumab 420mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 70 years STANDARD_DEVIATION 8 | 67 years STANDARD_DEVIATION 0 | 69 years STANDARD_DEVIATION 7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 1 |
| other Total, other adverse events | 1 / 3 | 0 / 1 |
| serious Total, serious adverse events | 1 / 3 | 0 / 1 |
Outcome results
Primary
Change From Baseline in Adenosine Diphosphate (ADP) Stimulated P-selectin Expression
Change from baseline in ADP-stimulated P-selectin expression (% Positive Cells) as measured by flow cytometry between treatment groups (420 mg evolocumab treatment and placebo).
Time frame: Baseline and after 30 days of treatment
Population: Instrument malfunction with flow cytometer. Unable to collect data from subject (n=1) in placebo group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab 420mg | Change From Baseline in Adenosine Diphosphate (ADP) Stimulated P-selectin Expression | Baseline | 45.2 % Positive Cells | Standard Deviation 17.1 |
| Evolocumab 420mg | Change From Baseline in Adenosine Diphosphate (ADP) Stimulated P-selectin Expression | 30 Days | 47.8 % Positive Cells | Standard Deviation 18.8 |
Secondary
Change in ADP-stimulated Cluster of Differentiation (CD)-147 MFI
Change in ADP-stimulated CD-147 mean fluorescence intensity (MFI) as measured by flow cytometry between treatment groups (420 mg evolocumab treatment and placebo)
Time frame: Baseline and after 30 days of treatment
Population: Instrument malfunction with flow cytometer. Unable to collect data from subject (n=1) in placebo group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab 420mg | Change in ADP-stimulated Cluster of Differentiation (CD)-147 MFI | Baseline | 1459 MFI | Standard Deviation 1220 |
| Evolocumab 420mg | Change in ADP-stimulated Cluster of Differentiation (CD)-147 MFI | 30 Days | 678 MFI | Standard Deviation 148 |
Secondary
Change in ADP-stimulated Lectin-like oxLDL [Oxidized Low-density Lipoprotein] Receptor-1 Mean Fluorescence Intensity (MFI)
Change in ADP-stimulated LOX-1 (MFI) as measured by flow cytometry between treatment groups (420 mg evolocumab treatment and placebo)
Time frame: Baseline and after 30 days of treatment
Population: Instrument malfunction with flow cytometer. Unable to collect data from subject (n=1) in placebo group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab 420mg | Change in ADP-stimulated Lectin-like oxLDL [Oxidized Low-density Lipoprotein] Receptor-1 Mean Fluorescence Intensity (MFI) | Baseline | 1186 MFI | Standard Deviation 1017 |
| Evolocumab 420mg | Change in ADP-stimulated Lectin-like oxLDL [Oxidized Low-density Lipoprotein] Receptor-1 Mean Fluorescence Intensity (MFI) | 30 Days | 721 MFI | Standard Deviation 82 |
Secondary
Change in ADP-unstimulated P-selectin Expression
Change in ADP-unstimulated P-selectin expression (% Positive Cells) between treatment groups (420 mg evolocumab treatment and placebo)
Time frame: Baseline and after 30 days of treatment
Population: Instrument malfunction with flow cytometer. Unable to collect data from subject (n=1) in placebo group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab 420mg | Change in ADP-unstimulated P-selectin Expression | Baseline | 5.4 % Positive Cells | Standard Deviation 2.7 |
| Evolocumab 420mg | Change in ADP-unstimulated P-selectin Expression | 30 Days | 8.8 % Positive Cells | Standard Deviation 2.9 |