Trial Outcomes & Findings for Antiplatelet Effects of Evolocumab in Patients With Peripheral Arterial Disease (NCT NCT03247972)
NCT ID: NCT03247972
Last Updated: 2024-02-16
Results Overview
Mean difference between 5uM ADP-induced % maximum platelet aggregation between V2 \[after run-in period / 8 weeks of HD statin therapy\] and V5 \[end of study/ 8 weeks o\]f continued HD statin therapy + evolocumab\]
Recruitment status
TERMINATED
Target enrollment
30 participants
Primary outcome timeframe
Change from week 8 (V2) to week 16 (V5)
Results posted on
2024-02-16
Participant Flow
Participant milestones
| Measure |
Patients With Peripheral Artery Disease Receiving Evolocumab + High Dose Statins
Adult patients with a history of Peripheral Artery Disease (PAD) defined as one or more of the following:
* Documented history of PAD
* Previous limb or foot amputation for arterial vascular disease (i.e., excludes trauma),
* Carotid artery disease (defined as \>50% stenosis or prior revascularization )
Evolocumab: Participants will be treated with high dose statins for 8 weeks followed by 8 weeks of high dose statin + evolocumab (420mg/4 wk) therapy.
|
|---|---|
|
High Dose Statin Run-In Period (8 Weeks)
STARTED
|
30
|
|
High Dose Statin Run-In Period (8 Weeks)
COMPLETED
|
26
|
|
High Dose Statin Run-In Period (8 Weeks)
NOT COMPLETED
|
4
|
|
High Dose Statins + Evolocumab (8 Weeks)
STARTED
|
26
|
|
High Dose Statins + Evolocumab (8 Weeks)
COMPLETED
|
24
|
|
High Dose Statins + Evolocumab (8 Weeks)
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Patients With Peripheral Artery Disease Receiving Evolocumab + High Dose Statins
Adult patients with a history of Peripheral Artery Disease (PAD) defined as one or more of the following:
* Documented history of PAD
* Previous limb or foot amputation for arterial vascular disease (i.e., excludes trauma),
* Carotid artery disease (defined as \>50% stenosis or prior revascularization )
Evolocumab: Participants will be treated with high dose statins for 8 weeks followed by 8 weeks of high dose statin + evolocumab (420mg/4 wk) therapy.
|
|---|---|
|
High Dose Statin Run-In Period (8 Weeks)
Withdrawal by Subject
|
4
|
|
High Dose Statins + Evolocumab (8 Weeks)
Withdrawal by Subject
|
2
|
Baseline Characteristics
Antiplatelet Effects of Evolocumab in Patients With Peripheral Arterial Disease
Baseline characteristics by cohort
| Measure |
Patients With Peripheral Artery Disease Receiving Evolocumab + High Dose Statins
n=30 Participants
Adult patients with a history of Peripheral Artery Disease (PAD) defined as one or more of the following:
* Documented history of PAD
* Previous limb or foot amputation for arterial vascular disease (i.e., excludes trauma),
* Carotid artery disease (defined as \>50% stenosis or prior revascularization )
Evolocumab: Sixty subjects will be treated with high dose statins for 8 weeks followed by 8 weeks of high dose statin + evolocumab (420mg/4 wk) therapy.
|
|---|---|
|
Age, Continuous
|
68.0 years
STANDARD_DEVIATION 8.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
23 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Change from week 8 (V2) to week 16 (V5)Mean difference between 5uM ADP-induced % maximum platelet aggregation between V2 \[after run-in period / 8 weeks of HD statin therapy\] and V5 \[end of study/ 8 weeks o\]f continued HD statin therapy + evolocumab\]
Outcome measures
| Measure |
Patients With Peripheral Artery Disease Receiving Evolocumab + High Dose Statins
n=24 Participants
Adult patients with a history of Peripheral Artery Disease (PAD) defined as one or more of the following:
* Documented history of PAD
* Previous limb or foot amputation for arterial vascular disease (i.e., excludes trauma),
* Carotid artery disease (defined as \>50% stenosis or prior revascularization )
Patients treated with high dose statins for 8 weeks followed by 8 weeks of high dose statin + evolocumab (420mg/4 wk) therapy.
|
|---|---|
|
Difference Between ADP-induced % Maximum Platelet Aggregation Between V2 (After 8 Weeks of HD Statin Therapy) and V5 (8 Weeks of Continued HD Statin Therapy + Evolocumab)
|
0.71 % maximum aggregation
Standard Deviation 10.8
|
SECONDARY outcome
Timeframe: Change from week 8 (v2) to week 16 (v5)Mean difference between 4ug Collagen-induced platelet aggregation (%) between V2 \[after run-in period / 8 weeks of HD statin therapy\] and V5 \[end of study/ 8 weeks of continued HD statin therapy + evolocumab\]
Outcome measures
| Measure |
Patients With Peripheral Artery Disease Receiving Evolocumab + High Dose Statins
n=24 Participants
Adult patients with a history of Peripheral Artery Disease (PAD) defined as one or more of the following:
* Documented history of PAD
* Previous limb or foot amputation for arterial vascular disease (i.e., excludes trauma),
* Carotid artery disease (defined as \>50% stenosis or prior revascularization )
Patients treated with high dose statins for 8 weeks followed by 8 weeks of high dose statin + evolocumab (420mg/4 wk) therapy.
|
|---|---|
|
Difference Between Collagen-induced Platelet Aggregation Between V2 (After 8 Weeks of HD Statin Therapy) and V5 (8 Weeks of Continued HD Statin Therapy + Evolocumab)
|
1.4 % maximum aggregation
Standard Deviation 17.7
|
SECONDARY outcome
Timeframe: Change from week 8 (v2) to week 16 (v5)Mean difference between SFFLRN-induced maximum platelet aggregation (%) between V2 \[after run-in period / 8 weeks of HD statin therapy\] and V5 \[end of study/ 8 weeks of continued HD statin therapy + evolocumab\]
Outcome measures
| Measure |
Patients With Peripheral Artery Disease Receiving Evolocumab + High Dose Statins
n=24 Participants
Adult patients with a history of Peripheral Artery Disease (PAD) defined as one or more of the following:
* Documented history of PAD
* Previous limb or foot amputation for arterial vascular disease (i.e., excludes trauma),
* Carotid artery disease (defined as \>50% stenosis or prior revascularization )
Patients treated with high dose statins for 8 weeks followed by 8 weeks of high dose statin + evolocumab (420mg/4 wk) therapy.
|
|---|---|
|
Difference Between SFFLRN-induced Platelet Aggregation Between V2 (After 8 Weeks of HD Statin Therapy) and V5 (8 Weeks of Continued HD Statin Therapy + Evolocumab)
|
6.8 % maximum aggregation
Standard Deviation 23.4
|
SECONDARY outcome
Timeframe: Change from week 8 (v2) to week 16 (v5)Population: Data not available from 3 participants due to laboratory equipment malfunction
Mean difference in activated % P-selectin positive platelets between V2 \[after run-in period / 8 weeks of HD statin therapy\] and V5 \[end of study/ 8 weeks o\]f continued HD statin therapy + evolocumab\]
Outcome measures
| Measure |
Patients With Peripheral Artery Disease Receiving Evolocumab + High Dose Statins
n=22 Participants
Adult patients with a history of Peripheral Artery Disease (PAD) defined as one or more of the following:
* Documented history of PAD
* Previous limb or foot amputation for arterial vascular disease (i.e., excludes trauma),
* Carotid artery disease (defined as \>50% stenosis or prior revascularization )
Patients treated with high dose statins for 8 weeks followed by 8 weeks of high dose statin + evolocumab (420mg/4 wk) therapy.
|
|---|---|
|
Difference Between Activated % P-selectin Positive Platelets Between V2 (After 8 Weeks of HD Statin Therapy) and V5 (8 Weeks of Continued HD Statin Therapy + Evolocumab)
|
126 % P-Selectin Positive Platelets
Standard Deviation 150
|
SECONDARY outcome
Timeframe: Change from week 8 (v2) to week 16 (v5)Mean difference TEG MAKH (platelet-fibrin clot strength) between V2 \[after run-in period / 8 weeks of HD statin therapy\] and V5 \[end of study/ 8 weeks of continued HD statin therapy + evolocumab\] Thromboelastography (TEG) is a viscoelastic hemostatic assay that measures the global viscoelastic properties of whole blood clot formation under low shear stress. TEG shows the interaction of platelets with the coagulation cascade (aggregation, clot strengthening, and fibrin cross-linking). MAKH is a measure of maximum platelet-fibrin clot strength. The normal range for MAKH is 53-68mm.
Outcome measures
| Measure |
Patients With Peripheral Artery Disease Receiving Evolocumab + High Dose Statins
n=24 Participants
Adult patients with a history of Peripheral Artery Disease (PAD) defined as one or more of the following:
* Documented history of PAD
* Previous limb or foot amputation for arterial vascular disease (i.e., excludes trauma),
* Carotid artery disease (defined as \>50% stenosis or prior revascularization )
Patients treated with high dose statins for 8 weeks followed by 8 weeks of high dose statin + evolocumab (420mg/4 wk) therapy.
|
|---|---|
|
Difference in TEG MAKH Between V2 (After 8 Weeks of HD Statin Therapy) and V5 (8 Weeks of Continued HD Statin Therapy + Evolocumab)
|
1.2 mm
Standard Deviation 3.2
|
Adverse Events
High Dose Statins (8 Weeks)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
High Dose Statins + Evolocumab (8 Weeks)
Serious events: 3 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
High Dose Statins (8 Weeks)
n=30 participants at risk
Participants treated with high dose statins for 8 weeks
|
High Dose Statins + Evolocumab (8 Weeks)
n=26 participants at risk
Participants treated with high dose statins + evolocumab (420mg/4 wk.) for the next 8 weeks.
|
|---|---|---|
|
Cardiac disorders
Cardiac intervention
|
0.00%
0/30 • 16 weeks
|
11.5%
3/26 • Number of events 6 • 16 weeks
|
Other adverse events
| Measure |
High Dose Statins (8 Weeks)
n=30 participants at risk
Participants treated with high dose statins for 8 weeks
|
High Dose Statins + Evolocumab (8 Weeks)
n=26 participants at risk
Participants treated with high dose statins + evolocumab (420mg/4 wk.) for the next 8 weeks.
|
|---|---|---|
|
Blood and lymphatic system disorders
Hyperglycemia
|
3.3%
1/30 • Number of events 1 • 16 weeks
|
7.7%
2/26 • Number of events 2 • 16 weeks
|
|
Immune system disorders
Allergic Rhinitis
|
0.00%
0/30 • 16 weeks
|
3.8%
1/26 • Number of events 1 • 16 weeks
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/30 • 16 weeks
|
3.8%
1/26 • Number of events 1 • 16 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis
|
0.00%
0/30 • 16 weeks
|
3.8%
1/26 • Number of events 1 • 16 weeks
|
|
Hepatobiliary disorders
Elevated Liver Enzymes
|
0.00%
0/30 • 16 weeks
|
3.8%
1/26 • Number of events 1 • 16 weeks
|
Additional Information
Director of Clinical Trials
Sinai Center for Thrombosis Research
Phone: 443-244-1497
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60