Trial Outcomes & Findings for Impact of Evolocumab on the Effects of Clopidogrel in Patients With High On-Treatment Platelet Reactivity (NCT NCT03096288)
NCT ID: NCT03096288
Last Updated: 2022-02-17
Results Overview
The primary end point of our study is the comparison of P2Y12 reaction units (PRU) measured by VerifyNow between evolocumab and placebo at 30 days after randomization. PRU is a well-established measure of platelet reactivity and aggregation in response to antiplatelet medications. The higher is the PRU the lower is the effect of the antiplatelet medication. HPR is defined as PRU\>208 and NPR as PRU 85-208.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
259 participants
Primary outcome timeframe
30 days
Results posted on
2022-02-17
Participant Flow
Patients were recruited between October 2017 and May 2020 at the University of Florida Health Science Center at UF Health Jacksonville - Division of Cardiology
259 patients were consented to participate in the study. Of these, 165 were screen failures and 10 withdrew consent before randomization. Thus, 84 patients were randomized and received study treatment.
Participant milestones
| Measure |
HPR - Evolocumab
Patients with high platelet reactivity (HPR) will be randomly assigned to receive a single dose of either evolocumab 420 mg s.c. or placebo (0.9% sodium chloride s.c. injection).
|
HPR - Placebo
Patients with high platelet reactivity (HPR) will be randomly assigned to receive a single dose of either evolocumab 420 mg s.c. or placebo (0.9% sodium chloride s.c. injection).
|
NPR - Evolocumab
Patients with normal platelet reactivity (NPR) will be randomly assigned to receive a single dose of either evolocumab 420 mg s.c. or placebo (0.9% sodium chloride s.c. injection).
|
NPR - Placebo
Patients with normal platelet reactivity (NPR) will be randomly assigned to receive a single dose of either evolocumab 420 mg s.c. or placebo (0.9% sodium chloride s.c. injection).
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
19
|
18
|
22
|
25
|
|
Overall Study
COMPLETED
|
19
|
17
|
22
|
24
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
1
|
Reasons for withdrawal
| Measure |
HPR - Evolocumab
Patients with high platelet reactivity (HPR) will be randomly assigned to receive a single dose of either evolocumab 420 mg s.c. or placebo (0.9% sodium chloride s.c. injection).
|
HPR - Placebo
Patients with high platelet reactivity (HPR) will be randomly assigned to receive a single dose of either evolocumab 420 mg s.c. or placebo (0.9% sodium chloride s.c. injection).
|
NPR - Evolocumab
Patients with normal platelet reactivity (NPR) will be randomly assigned to receive a single dose of either evolocumab 420 mg s.c. or placebo (0.9% sodium chloride s.c. injection).
|
NPR - Placebo
Patients with normal platelet reactivity (NPR) will be randomly assigned to receive a single dose of either evolocumab 420 mg s.c. or placebo (0.9% sodium chloride s.c. injection).
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
0
|
1
|
Baseline Characteristics
Impact of Evolocumab on the Effects of Clopidogrel in Patients With High On-Treatment Platelet Reactivity
Baseline characteristics by cohort
| Measure |
HPR - Evolocumab
n=19 Participants
Patients with high platelet reactivity (HPR) will be randomly assigned to receive a single dose of either evolocumab 420 mg s.c. or placebo (0.9% sodium chloride s.c. injection).
|
HPR - Placebo
n=18 Participants
Patients with high platelet reactivity (HPR) will be randomly assigned to receive a single dose of either evolocumab 420 mg s.c. or placebo (0.9% sodium chloride s.c. injection).
|
NPR - Evolocumab
n=22 Participants
Patients with normal platelet reactivity (NPR) will be randomly assigned to receive a single dose of either evolocumab 420 mg s.c. or placebo (0.9% sodium chloride s.c. injection).
|
NPR - Placebo
n=25 Participants
Patients with normal platelet reactivity (NPR) will be randomly assigned to receive a single dose of either evolocumab 420 mg s.c. or placebo (0.9% sodium chloride s.c. injection).
|
Total
n=84 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
63 years
STANDARD_DEVIATION 8 • n=99 Participants
|
62 years
STANDARD_DEVIATION 8 • n=107 Participants
|
63 years
STANDARD_DEVIATION 8 • n=206 Participants
|
58 years
STANDARD_DEVIATION 8 • n=7 Participants
|
62 years
STANDARD_DEVIATION 8 • n=31 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
8 Participants
n=7 Participants
|
32 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
17 Participants
n=7 Participants
|
52 Participants
n=31 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Black or African American
|
15 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
10 Participants
n=7 Participants
|
46 Participants
n=31 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
14 Participants
n=7 Participants
|
36 Participants
n=31 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=31 Participants
|
|
LDL cholesterol
|
107 mg/dL
STANDARD_DEVIATION 29 • n=99 Participants
|
109 mg/dL
STANDARD_DEVIATION 42 • n=107 Participants
|
91 mg/dL
STANDARD_DEVIATION 30 • n=206 Participants
|
99 mg/dL
STANDARD_DEVIATION 31 • n=7 Participants
|
101 mg/dL
STANDARD_DEVIATION 33 • n=31 Participants
|
PRIMARY outcome
Timeframe: 30 daysPopulation: Patient with valid data at 30 days were analyzed
The primary end point of our study is the comparison of P2Y12 reaction units (PRU) measured by VerifyNow between evolocumab and placebo at 30 days after randomization. PRU is a well-established measure of platelet reactivity and aggregation in response to antiplatelet medications. The higher is the PRU the lower is the effect of the antiplatelet medication. HPR is defined as PRU\>208 and NPR as PRU 85-208.
Outcome measures
| Measure |
NPR - Evolocumab
n=22 Participants
Patients with normal platelet reactivity (NPR) will be randomly assigned to receive a single dose of either evolocumab 420 mg s.c. or placebo (0.9% sodium chloride s.c. injection).
|
NPR - Placebo
n=24 Participants
Patients with normal platelet reactivity (NPR) will be randomly assigned to receive a single dose of either evolocumab 420 mg s.c. or placebo (0.9% sodium chloride s.c. injection).
|
HPR - Evolocumab
n=19 Participants
Patients with high platelet reactivity (HPR) will be randomly assigned to receive a single dose of either evolocumab 420 mg s.c. or placebo (0.9% sodium chloride s.c. injection).
|
HPR - Placebo
n=17 Participants
Patients with high platelet reactivity (HPR) will be randomly assigned to receive a single dose of either evolocumab 420 mg s.c. or placebo (0.9% sodium chloride s.c. injection).
|
|---|---|---|---|---|
|
Platelet Reactivity Defined by VerifyNow PRU in HPR and NPR Patients
|
141 PRU
Standard Deviation 54
|
159 PRU
Standard Deviation 41
|
219 PRU
Standard Deviation 38
|
241 PRU
Standard Deviation 52
|
Adverse Events
HPR - Evolocumab
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
HPR - Placebo
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
NPR - Evolocumab
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
NPR - Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
HPR - Evolocumab
n=19 participants at risk
Evolocumab (Repatha) 420 mg s.c. single injection
Evolocumab: Patients will be randomly assigned to receive a single dose of either evolocumab 420 mg s.c. or placebo (0.9% sodium chloride s.c. injection).
|
HPR - Placebo
n=18 participants at risk
0.9% sodium chloride s.c. single injection
Placebo: Patients will be randomly assigned to receive a single dose of either evolocumab 420 mg s.c. or placebo (0.9% sodium chloride s.c. injection).
|
NPR - Evolocumab
n=22 participants at risk
Evolocumab (Repatha) 420 mg s.c. single injection
Evolocumab: Patients will be randomly assigned to receive a single dose of either evolocumab 420 mg s.c. or placebo (0.9% sodium chloride s.c. injection).
|
NPR - Placebo
n=25 participants at risk
0.9% sodium chloride s.c. single injection
Placebo: Patients will be randomly assigned to receive a single dose of either evolocumab 420 mg s.c. or placebo (0.9% sodium chloride s.c. injection).
|
|---|---|---|---|---|
|
Cardiac disorders
myocardial infarction
|
0.00%
0/19 • 30 days
Non serious adverse events are reported only if frequency \>5%.
|
5.6%
1/18 • Number of events 1 • 30 days
Non serious adverse events are reported only if frequency \>5%.
|
0.00%
0/22 • 30 days
Non serious adverse events are reported only if frequency \>5%.
|
0.00%
0/25 • 30 days
Non serious adverse events are reported only if frequency \>5%.
|
|
Cardiac disorders
chest pain
|
5.3%
1/19 • Number of events 1 • 30 days
Non serious adverse events are reported only if frequency \>5%.
|
0.00%
0/18 • 30 days
Non serious adverse events are reported only if frequency \>5%.
|
0.00%
0/22 • 30 days
Non serious adverse events are reported only if frequency \>5%.
|
0.00%
0/25 • 30 days
Non serious adverse events are reported only if frequency \>5%.
|
|
Gastrointestinal disorders
gastrointestinal bleeding
|
5.3%
1/19 • Number of events 1 • 30 days
Non serious adverse events are reported only if frequency \>5%.
|
0.00%
0/18 • 30 days
Non serious adverse events are reported only if frequency \>5%.
|
4.5%
1/22 • Number of events 1 • 30 days
Non serious adverse events are reported only if frequency \>5%.
|
0.00%
0/25 • 30 days
Non serious adverse events are reported only if frequency \>5%.
|
Other adverse events
Adverse event data not reported
Additional Information
Dominick J. Angiolillo, MD, PhD
University of Florida College of Medicine - Jacksonville
Phone: +1-904-244-3378
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place