Trial Outcomes & Findings for Effect of Evolocumab on Coronary Atherosclerosis (NCT NCT03689946)

NCT ID: NCT03689946

Last Updated: 2024-07-17

Results Overview

Compare NCPV in mm\^3 measured on cardiac CT images as analyzed by quantitative software between the two assessments

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

55 participants

Primary outcome timeframe

baseline (pre-treatment) and 18 months after of treatment

Results posted on

2024-07-17

Participant Flow

Participant milestones

Participant milestones
Measure
Evolocumab, F18-NaF PET, CCTA
Evolocumab self-administration for 18 months. Baseline (pre-treatment) and follow-up 18F-NaF PET and CCTA (possible beta-blocker and nitroglycerin, if medically safe). Evolocumab: Evolocumab: In patients without homozygous familial hypercholesterolemia (FH), evolocumab will be self-injected as follows: 140mg every 2 weeks or 420mg once a month subcutaneously. Patients with homozygous FH will be instructed to administer 420mg subcutaneously once a month by giving 3 injections consecutively within 30 minutes using the single-use prefilled autoinjector. 18F-NaF PET: 18F-NaF PET: Baseline (pre-treatment) and follow-up dual cardiac and respiratory-gated PET- imaging of the thoracic aorta. Dose of 250 MBq 18F-NaF intravenously. CCTA: CCTA: Baseline (pre-treatment) and follow-up CCTA. Bolus injection of 80-100 ml contrast (Omnipaque or Visipaque). Possible beta blocker(metoprolol)administered to achieve a target heart ≤70 beats/min (bpm) and/or 0.4 or 0.8 mg of sublingual nitroglycerin administered, if medical safe. Omnipaque: contrast agent for CCTA Metoprolol: beta blocker to optimize heart rate during CCTA Nitroglycerin: premedication for CCTA
Overall Study
STARTED
55
Overall Study
COMPLETED
47
Overall Study
NOT COMPLETED
8

Reasons for withdrawal

Reasons for withdrawal
Measure
Evolocumab, F18-NaF PET, CCTA
Evolocumab self-administration for 18 months. Baseline (pre-treatment) and follow-up 18F-NaF PET and CCTA (possible beta-blocker and nitroglycerin, if medically safe). Evolocumab: Evolocumab: In patients without homozygous familial hypercholesterolemia (FH), evolocumab will be self-injected as follows: 140mg every 2 weeks or 420mg once a month subcutaneously. Patients with homozygous FH will be instructed to administer 420mg subcutaneously once a month by giving 3 injections consecutively within 30 minutes using the single-use prefilled autoinjector. 18F-NaF PET: 18F-NaF PET: Baseline (pre-treatment) and follow-up dual cardiac and respiratory-gated PET- imaging of the thoracic aorta. Dose of 250 MBq 18F-NaF intravenously. CCTA: CCTA: Baseline (pre-treatment) and follow-up CCTA. Bolus injection of 80-100 ml contrast (Omnipaque or Visipaque). Possible beta blocker(metoprolol)administered to achieve a target heart ≤70 beats/min (bpm) and/or 0.4 or 0.8 mg of sublingual nitroglycerin administered, if medical safe. Omnipaque: contrast agent for CCTA Metoprolol: beta blocker to optimize heart rate during CCTA Nitroglycerin: premedication for CCTA
Overall Study
Withdrawal by Subject
3
Overall Study
Lost to Follow-up
3
Overall Study
Data corruption
2

Baseline Characteristics

Effect of Evolocumab on Coronary Atherosclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Evolocumab, F18-NaF PET, CCTA
n=47 Participants
Evolocumab self-administration for 18 months. Baseline (pre-treatment) and follow-up 18F-NaF PET and CCTA (possible beta-blocker and nitroglycerin, if medically safe). Evolocumab: Evolocumab: In patients without homozygous familial hypercholesterolemia (FH), evolocumab will be self-injected as follows: 140mg every 2 weeks or 420mg once a month subcutaneously. Patients with homozygous FH will be instructed to administer 420mg subcutaneously once a month by giving 3 injections consecutively within 30 minutes using the single-use prefilled autoinjector. 18F-NaF PET: 18F-NaF PET: Baseline (pre-treatment) and follow-up dual cardiac and respiratory-gated PET- imaging of the thoracic aorta. Dose of 250 MBq 18F-NaF intravenously. CCTA: CCTA: Baseline (pre-treatment) and follow-up CCTA. Bolus injection of 80-100 ml contrast (Omnipaque or Visipaque). Possible beta blocker(metoprolol)administered to achieve a target heart ≤70 beats/min (bpm) and/or 0.4 or 0.8 mg of sublingual nitroglycerin administered, if medical safe. Omnipaque: contrast agent for CCTA Metoprolol: beta blocker to optimize heart rate during CCTA Nitroglycerin: premedication for CCTA
Age, Categorical
<=18 years
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
25 Participants
n=5 Participants
Age, Categorical
>=65 years
22 Participants
n=5 Participants
Age, Continuous
61.8 years
STANDARD_DEVIATION 10.1 • n=5 Participants
Sex: Female, Male
Female
6 Participants
n=5 Participants
Sex: Female, Male
Male
41 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
2 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
45 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 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
0 Participants
n=5 Participants
Race (NIH/OMB)
White
40 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
3 Participants
n=5 Participants
Region of Enrollment
United States
47 participants
n=5 Participants
BMI
26.8 kg/m^2
STANDARD_DEVIATION 4.4 • n=5 Participants
Risk factors
Hypertension
25 Participants
n=5 Participants
Risk factors
Diabetes
10 Participants
n=5 Participants
Risk factors
Hypercholesterolemia
42 Participants
n=5 Participants
Risk factors
Current smoker
1 Participants
n=5 Participants
Risk factors
Prior CAD history
4 Participants
n=5 Participants
Risk factors
Prior CVA history
1 Participants
n=5 Participants
Medication
Aspirin
29 Participants
n=5 Participants
Medication
Statin
38 Participants
n=5 Participants
Medication
ACEi or ARB
15 Participants
n=5 Participants
Medication
Beta blocker
17 Participants
n=5 Participants
Medication
Calcium channel blocker
7 Participants
n=5 Participants
Plaque volume
Total plaque volume
716 mm^3
STANDARD_DEVIATION 431 • n=5 Participants
Plaque volume
Non calcified plaque volume
607 mm^3
STANDARD_DEVIATION 347 • n=5 Participants
Plaque volume
Low density non calcified plaque volume
37 mm^3
STANDARD_DEVIATION 29 • n=5 Participants
Plaque volume
Calcified plaque volume
109 mm^3
STANDARD_DEVIATION 134 • n=5 Participants
Cholesterol level
Total choleseterol
155.8 mg/dL
STANDARD_DEVIATION 46.1 • n=5 Participants
Cholesterol level
LDL cholesterol
82.2 mg/dL
STANDARD_DEVIATION 38.9 • n=5 Participants
Cholesterol level
HDL cholesterol
47.9 mg/dL
STANDARD_DEVIATION 14.4 • n=5 Participants
Cholesterol level
Triglycerides
137.6 mg/dL
STANDARD_DEVIATION 81.5 • n=5 Participants

PRIMARY outcome

Timeframe: baseline (pre-treatment) and 18 months after of treatment

Compare NCPV in mm\^3 measured on cardiac CT images as analyzed by quantitative software between the two assessments

Outcome measures

Outcome measures
Measure
Evolocumab, F18-NaF PET, CCTA
n=47 Participants
Evolocumab self-administration for 18 months. Baseline (pre-treatment) and follow-up 18F-NaF PET and CCTA (possible beta-blocker and nitroglycerin, if medically safe). Evolocumab: Evolocumab: In patients without homozygous familial hypercholesterolemia (FH), evolocumab will be self-injected as follows: 140mg every 2 weeks or 420mg once a month subcutaneously. Patients with homozygous FH will be instructed to administer 420mg subcutaneously once a month by giving 3 injections consecutively within 30 minutes using the single-use prefilled autoinjector. 18F-NaF PET: 18F-NaF PET: Baseline (pre-treatment) and follow-up dual cardiac and respiratory-gated PET- imaging of the thoracic aorta. Dose of 250 MBq 18F-NaF intravenously. CCTA: CCTA: Baseline (pre-treatment) and follow-up CCTA. Bolus injection of 80-100 ml contrast (Omnipaque or Visipaque). Possible beta blocker(metoprolol)administered to achieve a target heart ≤70 beats/min (bpm) and/or 0.4 or 0.8 mg of sublingual nitroglycerin administered, if medical safe. Omnipaque: contrast agent for CCTA Metoprolol: beta blocker to optimize heart rate during CCTA Nitroglycerin: premedication for CCTA
Change in Noncalcified Coronary Artery Plaque Volume (NCPV)
-45 mm^3
Standard Deviation 64

SECONDARY outcome

Timeframe: baseline (pre-treatment) and 18 months after of treatment

Chances in volume of type of plaque (total, calcified, low density non calcified) on cardiac CT images as detected by quantitative software between the two assessments

Outcome measures

Outcome measures
Measure
Evolocumab, F18-NaF PET, CCTA
n=47 Participants
Evolocumab self-administration for 18 months. Baseline (pre-treatment) and follow-up 18F-NaF PET and CCTA (possible beta-blocker and nitroglycerin, if medically safe). Evolocumab: Evolocumab: In patients without homozygous familial hypercholesterolemia (FH), evolocumab will be self-injected as follows: 140mg every 2 weeks or 420mg once a month subcutaneously. Patients with homozygous FH will be instructed to administer 420mg subcutaneously once a month by giving 3 injections consecutively within 30 minutes using the single-use prefilled autoinjector. 18F-NaF PET: 18F-NaF PET: Baseline (pre-treatment) and follow-up dual cardiac and respiratory-gated PET- imaging of the thoracic aorta. Dose of 250 MBq 18F-NaF intravenously. CCTA: CCTA: Baseline (pre-treatment) and follow-up CCTA. Bolus injection of 80-100 ml contrast (Omnipaque or Visipaque). Possible beta blocker(metoprolol)administered to achieve a target heart ≤70 beats/min (bpm) and/or 0.4 or 0.8 mg of sublingual nitroglycerin administered, if medical safe. Omnipaque: contrast agent for CCTA Metoprolol: beta blocker to optimize heart rate during CCTA Nitroglycerin: premedication for CCTA
Change in Plaque Composition (Total, Calcified, Low Density Non Calcified)
Changes in total plaque volume
-5 mm^3
Standard Deviation 97
Change in Plaque Composition (Total, Calcified, Low Density Non Calcified)
Changes in calcified plaque volume
40 mm^3
Standard Deviation 56
Change in Plaque Composition (Total, Calcified, Low Density Non Calcified)
Changes in low density non calcified plaque volume
-17 mm^3
Standard Deviation 24

Adverse Events

Evolocumab, F18-NaF PET, CCTA

Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Evolocumab, F18-NaF PET, CCTA
n=55 participants at risk
Evolocumab self-administration for 18 months. Baseline (pre-treatment) and follow-up 18F-NaF PET and CCTA (possible beta-blocker and nitroglycerin, if medically safe). Evolocumab: Evolocumab: In patients without homozygous familial hypercholesterolemia (FH), evolocumab will be self-injected as follows: 140mg every 2 weeks or 420mg once a month subcutaneously. Patients with homozygous FH will be instructed to administer 420mg subcutaneously once a month by giving 3 injections consecutively within 30 minutes using the single-use prefilled autoinjector. 18F-NaF PET: 18F-NaF PET: Baseline (pre-treatment) and follow-up dual cardiac and respiratory-gated PET- imaging of the thoracic aorta. Dose of 250 MBq 18F-NaF intravenously. CCTA: CCTA: Baseline (pre-treatment) and follow-up CCTA. Bolus injection of 80-100 ml contrast (Omnipaque or Visipaque). Possible beta blocker(metoprolol)administered to achieve a target heart ≤70 beats/min (bpm) and/or 0.4 or 0.8 mg of sublingual nitroglycerin administered, if medical safe. Omnipaque: contrast agent for CCTA Metoprolol: beta blocker to optimize heart rate during CCTA Nitroglycerin: premedication for CCTA
Respiratory, thoracic and mediastinal disorders
runny nose
5.5%
3/55 • Number of events 3 • Duration of the study (18 months)
Only adverse events that occurred in at least 5% of the cohort were reported.

Additional Information

Daniel Berman

Cedars-Sinai Medical Center

Phone: 310-423-4224

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place