Trial Outcomes & Findings for Cardiac Allograft Vasculopathy Inhibition With Alirocumab (NCT NCT03537742)

NCT ID: NCT03537742

Last Updated: 2026-08-18

Results Overview

Coronary artery plaque volume (mm³) was assessed using intravascular ultrasound (IVUS) during coronary angiography. Measurements were obtained at baseline (prior to study drug randomization) and at 1 year following treatment. The outcome measure represents the change in plaque volume from baseline to 1 year.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

114 participants

Primary outcome timeframe

Baseline to one year

Results posted on

2026-08-18

Participant Flow

Participants were recruited between 2019 and 2024 at Stanford University and Kaiser Permanente Santa Clara Medical Center. Eligible adult heart transplant recipients were screened soon after transplantation. A total of one hundred fourteen participants were enrolled and randomized in a 1:1 ratio to alirocumab or placebo following a baseline coronary catheterization procedure.

Eligible participants were adults ≥18 years old and had undergone heart transplantation. Before randomization, participants completed baseline coronary angiography, intravascular ultrasound, physiologic assessment, and lipid testing. All participants had rosuvastatin prescribed therapy prior to joining the study.

Participant milestones

Participant milestones
Measure
Alirocumab
Alirocumab 150 mg subcutaneously every 2 weeks for one year.
Placebo
placebo to match alirocumab, subcutaneous every 2 weeks for one year.
Overall Study
STARTED
57
57
Overall Study
COMPLETED
57
57
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Cardiac Allograft Vasculopathy Inhibition With Alirocumab

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Alirocumab
n=57 Participants
alirocumab 150mg subcutaneous every other week for one year following start of study drug
Placebo
n=57 Participants
placebo to match alirocumab every other week for one year following start of study drug
Total
n=114 Participants
Total of all reporting groups
Age, Continuous
51.4 years
STANDARD_DEVIATION 16.4 • n=298 Participants
55.2 years
STANDARD_DEVIATION 10.8 • n=102 Participants
53.3 years
STANDARD_DEVIATION 14.0 • n=400 Participants
Sex: Female, Male
Female
10 Participants
n=298 Participants
12 Participants
n=102 Participants
22 Participants
n=400 Participants
Sex: Female, Male
Male
47 Participants
n=298 Participants
45 Participants
n=102 Participants
92 Participants
n=400 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
15 Participants
n=298 Participants
10 Participants
n=102 Participants
25 Participants
n=400 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
42 Participants
n=298 Participants
47 Participants
n=102 Participants
89 Participants
n=400 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=298 Participants
0 Participants
n=102 Participants
0 Participants
n=400 Participants
Race (NIH/OMB)
American Indian or Alaska Native
1 Participants
n=298 Participants
0 Participants
n=102 Participants
1 Participants
n=400 Participants
Race (NIH/OMB)
Asian
7 Participants
n=298 Participants
9 Participants
n=102 Participants
16 Participants
n=400 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=298 Participants
2 Participants
n=102 Participants
2 Participants
n=400 Participants
Race (NIH/OMB)
Black or African American
4 Participants
n=298 Participants
8 Participants
n=102 Participants
12 Participants
n=400 Participants
Race (NIH/OMB)
White
32 Participants
n=298 Participants
31 Participants
n=102 Participants
63 Participants
n=400 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=298 Participants
0 Participants
n=102 Participants
0 Participants
n=400 Participants
Race (NIH/OMB)
Unknown or Not Reported
13 Participants
n=298 Participants
7 Participants
n=102 Participants
20 Participants
n=400 Participants
Region of Enrollment
United States
57 Participants
n=298 Participants
57 Participants
n=102 Participants
114 Participants
n=400 Participants
Comorbidities
CMV IgG positive
36 Participants
n=298 Participants
34 Participants
n=102 Participants
70 Participants
n=400 Participants
Comorbidities
Diabetes
25 Participants
n=298 Participants
27 Participants
n=102 Participants
52 Participants
n=400 Participants
Comorbidities
Hypertension
45 Participants
n=298 Participants
48 Participants
n=102 Participants
93 Participants
n=400 Participants
Comorbidities
Hypercholesterolemia
36 Participants
n=298 Participants
37 Participants
n=102 Participants
73 Participants
n=400 Participants
Comorbidities
Ischemic cardiomyopathy
13 Participants
n=298 Participants
6 Participants
n=102 Participants
19 Participants
n=400 Participants

PRIMARY outcome

Timeframe: Baseline to one year

Population: Intention-to-treat population.

Coronary artery plaque volume (mm³) was assessed using intravascular ultrasound (IVUS) during coronary angiography. Measurements were obtained at baseline (prior to study drug randomization) and at 1 year following treatment. The outcome measure represents the change in plaque volume from baseline to 1 year.

Outcome measures

Outcome measures
Measure
Alirocumab
n=57 Participants
Alirocumab 150 mg subcutaneously every 2 weeks for one year.
Placebo
n=57 Participants
placebo to match alirocumab, subcutaneous every 2 weeks for one year.
Plaque Volume
One year
184.5 mm^3
Standard Deviation 105.4
183.1 mm^3
Standard Deviation 109.8
Plaque Volume
Baseline
176.3 mm^3
Standard Deviation 95.2
173.7 mm^3
Standard Deviation 96.7

SECONDARY outcome

Timeframe: Baseline and one year

Population: The analysis was conducted according to the intention-to-treat (ITT) principle, utilizing a linear mixed-effects model to account for repeated measurements

Low-density lipoprotein cholesterol (LDL-C) levels were assessed at baseline and at 1 year post-randomization to compare the lipid-lowering effectiveness of adding alirocumab to standard rosuvastatin therapy versus placebo. Results are reported as mean +/- standard deviation (SD).

Outcome measures

Outcome measures
Measure
Alirocumab
n=57 Participants
Alirocumab 150 mg subcutaneously every 2 weeks for one year.
Placebo
n=57 Participants
placebo to match alirocumab, subcutaneous every 2 weeks for one year.
Low-Density Lipoprotein Cholesterol (LDL-C) Levels
Baseline
72.7 mg/dL
Standard Deviation 31.7
69.0 mg/dL
Standard Deviation 22.4
Low-Density Lipoprotein Cholesterol (LDL-C) Levels
One year
31.5 mg/dL
Standard Deviation 20.7
69.2 mg/dL
Standard Deviation 28.1

SECONDARY outcome

Timeframe: Baseline and 1 year

Population: Intention-to-treat population, analyzed using a linear mixed-effects model to account for repeated measurements.

Apolipoprotein B was measured in mg/dL at baseline and 1 year to evaluate the impact of alirocumab versus placebo on overall atherogenic particle burden.

Outcome measures

Outcome measures
Measure
Alirocumab
n=57 Participants
Alirocumab 150 mg subcutaneously every 2 weeks for one year.
Placebo
n=57 Participants
placebo to match alirocumab, subcutaneous every 2 weeks for one year.
Apolipoprotein B (ApoB)
Baseline
73.8 mg/dL
Standard Deviation 20.8
68.2 mg/dL
Standard Deviation 17.3
Apolipoprotein B (ApoB)
One year
39.6 mg/dL
Standard Deviation 17.4
70.1 mg/dL
Standard Deviation 25.3

SECONDARY outcome

Timeframe: Baseline and 1 year

Population: Intention-to-treat population, analyzed using a linear mixed-effects model to account for repeated measurements.

Lipoprotein(a) was measured at baseline and 1 year to assess the efficacy of alirocumab in lowering this specific lipid parameter.

Outcome measures

Outcome measures
Measure
Alirocumab
n=57 Participants
Alirocumab 150 mg subcutaneously every 2 weeks for one year.
Placebo
n=57 Participants
placebo to match alirocumab, subcutaneous every 2 weeks for one year.
Lipoprotein(a)
Baseline
43.5 mg/dL
Standard Deviation 52.3
54.4 mg/dL
Standard Deviation 64.6
Lipoprotein(a)
One year
27.9 mg/dL
Standard Deviation 39.9
49.2 mg/dL
Standard Deviation 56.2

SECONDARY outcome

Timeframe: Baseline and one year

Population: Intention-to-treat population, analyzed using a linear mixed-effects model to account for repeated measurements.

Total cholesterol was measured to assess the efficacy of alirocumab versus placebo on overall impact for this specific lipid parameter.

Outcome measures

Outcome measures
Measure
Alirocumab
n=57 Participants
Alirocumab 150 mg subcutaneously every 2 weeks for one year.
Placebo
n=57 Participants
placebo to match alirocumab, subcutaneous every 2 weeks for one year.
Total Cholesterol
Baseline
157.8 mg/dL
Standard Deviation 36.0
150.4 mg/dL
Standard Deviation 30.6
Total Cholesterol
One year
94.2 mg/dL
Standard Deviation 26.3
140.1 mg/dL
Standard Deviation 41.3

SECONDARY outcome

Timeframe: Baseline and one year

Population: Intention-to-treat population, analyzed using a linear mixed-effects model to account for repeated measurements.

HDL cholesterol was measured to assess the efficacy of alirocumab versus placebo on overall impact for this specific lipid parameter.

Outcome measures

Outcome measures
Measure
Alirocumab
n=57 Participants
Alirocumab 150 mg subcutaneously every 2 weeks for one year.
Placebo
n=57 Participants
placebo to match alirocumab, subcutaneous every 2 weeks for one year.
HDL Cholesterol
Baseline
64.6 mg/dL
Standard Deviation 20.7
59.8 mg/dL
Standard Deviation 17.5
HDL Cholesterol
One year
48.2 mg/dL
Standard Deviation 13.4
46.3 mg/dL
Standard Deviation 10.9

SECONDARY outcome

Timeframe: Baseline and one year

Population: Intention-to-treat population, analyzed using a linear mixed-effects model to account for repeated measurements.

Triglycerides were measured to assess the efficacy of alirocumab versus placebo on overall impact for this specific lipid parameter.

Outcome measures

Outcome measures
Measure
Alirocumab
n=57 Participants
Alirocumab 150 mg subcutaneously every 2 weeks for one year.
Placebo
n=57 Participants
placebo to match alirocumab, subcutaneous every 2 weeks for one year.
Triglycerides
One year
123.1 mg/dL
Standard Deviation 69.3
160.0 mg/dL
Standard Deviation 171.4
Triglycerides
Baseline
153.2 mg/dL
Standard Deviation 69.3
155.9 mg/dL
Standard Deviation 109.2

SECONDARY outcome

Timeframe: Baseline and one year

Population: Intention-to-treat population, analyzed using a linear mixed-effects model to account for repeated measurements.

hs-CRP was measured to assess the efficacy of alirocumab versus placebo on overall impact for this specific lipid parameter

Outcome measures

Outcome measures
Measure
Alirocumab
n=57 Participants
Alirocumab 150 mg subcutaneously every 2 weeks for one year.
Placebo
n=57 Participants
placebo to match alirocumab, subcutaneous every 2 weeks for one year.
High-sensitivity C-reactive Protein (Hs-CRP)
Baseline
5.8 mg/L
Standard Deviation 15.1
3.8 mg/L
Standard Deviation 7.6
High-sensitivity C-reactive Protein (Hs-CRP)
One year
8.3 mg/L
Standard Deviation 27.4
3.4 mg/L
Standard Deviation 3.1

SECONDARY outcome

Timeframe: baseline and one year

Population: Intention-to-treat population including all randomized participants with available physiological data.

FFR measures the exact severity of blood flow restriction in a narrowed coronary artery. It is calculated as the mean distal pressure divided by the mean proximal pressure during maximal hyperemia.

Outcome measures

Outcome measures
Measure
Alirocumab
n=57 Participants
Alirocumab 150 mg subcutaneously every 2 weeks for one year.
Placebo
n=57 Participants
placebo to match alirocumab, subcutaneous every 2 weeks for one year.
Fractional Flow Reserve (FFR)
Baseline
0.90 ratio
Standard Deviation 0.03
0.90 ratio
Standard Deviation 0.04
Fractional Flow Reserve (FFR)
One year
0.90 ratio
Standard Deviation 0.04
0.89 ratio
Standard Deviation 0.05

SECONDARY outcome

Timeframe: Baseline and 1 year

Population: Intention-to-treat population including all randomized participants with available physiological data.

CFR is the ratio of maximal coronary blood flow to resting blood flow. It was calculated as the resting mean transit time divided by the hyperemic mean transit time.

Outcome measures

Outcome measures
Measure
Alirocumab
n=57 Participants
Alirocumab 150 mg subcutaneously every 2 weeks for one year.
Placebo
n=57 Participants
placebo to match alirocumab, subcutaneous every 2 weeks for one year.
Coronary Flow Reserve (CFR)
Baseline
4.5 ratio
Standard Deviation 1.9
4.2 ratio
Standard Deviation 1.8
Coronary Flow Reserve (CFR)
One year
4.6 ratio
Standard Deviation 2.0
5.1 ratio
Standard Deviation 2.3

SECONDARY outcome

Timeframe: Baseline and 1 year

Population: Intention-to-treat population including all randomized participants with available physiological data.

IMR is used to assess the function of the coronary microvasculature. It is calculated as the hyperemic distal coronary pressure multiplied by the hyperemic mean transit time.

Outcome measures

Outcome measures
Measure
Alirocumab
n=57 Participants
Alirocumab 150 mg subcutaneously every 2 weeks for one year.
Placebo
n=57 Participants
placebo to match alirocumab, subcutaneous every 2 weeks for one year.
Index of Microcirculatory Resistance (IMR)
Baseline
15.6 mmHg·s
Standard Deviation 6.6
14.6 mmHg·s
Standard Deviation 5.9
Index of Microcirculatory Resistance (IMR)
One year
15.4 mmHg·s
Standard Deviation 8.9
15.4 mmHg·s
Standard Deviation 7.5

SECONDARY outcome

Timeframe: Baseline and 1 year

Population: Intention-to-treat population, analyzed using a linear mixed-effects model to account for repeated measurements.

LCBI is a measure of the lipid content within the coronary artery wall. It is calculated as the fraction of valid pixels with a yellow (high lipid probability) signal \>0.6, multiplied by 1000. Values range from 0 to 1000, where higher values indicate a greater lipid burden.

Outcome measures

Outcome measures
Measure
Alirocumab
n=57 Participants
Alirocumab 150 mg subcutaneously every 2 weeks for one year.
Placebo
n=57 Participants
placebo to match alirocumab, subcutaneous every 2 weeks for one year.
Lipid Core Burden Index (LCBI)
Baseline
2.3 Score on a scale
Standard Deviation 6.8
4.6 Score on a scale
Standard Deviation 15.8
Lipid Core Burden Index (LCBI)
One year
1.9 Score on a scale
Standard Deviation 6.5
1.7 Score on a scale
Standard Deviation 3.5

SECONDARY outcome

Timeframe: Baseline and 1 year

Population: Intention-to-treat (ITT) population, analyzed using a linear mixed-effects model to account for repeated measurements

The maxLCBI 4-mm represents the highest lipid core burden index (LCBI) value within any contiguous 4-mm segment of the scanned coronary region, indicating the most lipid-rich portion of the plaque. Scores range from 0 to 1000. Higher scores indicate greater lipid burden (worse outcome), while lower scores indicate less lipid-rich plaque (better outcome).

Outcome measures

Outcome measures
Measure
Alirocumab
n=57 Participants
Alirocumab 150 mg subcutaneously every 2 weeks for one year.
Placebo
n=57 Participants
placebo to match alirocumab, subcutaneous every 2 weeks for one year.
Maximum Lipid Core Burden Index in 4 mm (maxLCBI 4mm)
One year
19.3 Score on a scale
Standard Deviation 69.4
19.6 Score on a scale
Standard Deviation 40.0
Maximum Lipid Core Burden Index in 4 mm (maxLCBI 4mm)
Baseline
21.0 Score on a scale
Standard Deviation 64.2
36.1 Score on a scale
Standard Deviation 76.4

SECONDARY outcome

Timeframe: Baseline and 1 year

Population: Intention-to-treat population, analyzed using a linear mixed-effects model to account for repeated measurements.

Measured using intravascular ultrasound (IVUS), this represents the thickness of the innermost layer of the artery wall at its thickest point.

Outcome measures

Outcome measures
Measure
Alirocumab
n=57 Participants
Alirocumab 150 mg subcutaneously every 2 weeks for one year.
Placebo
n=57 Participants
placebo to match alirocumab, subcutaneous every 2 weeks for one year.
Maximum Intimal Thickness (MIT)
Baseline
0.90 mm (millimeters)
Standard Deviation 0.50
0.87 mm (millimeters)
Standard Deviation 0.49
Maximum Intimal Thickness (MIT)
One year
1.1 mm (millimeters)
Standard Deviation 0.53
1.1 mm (millimeters)
Standard Deviation 0.62

Adverse Events

Alirocumab

Serious events: 17 serious events
Other events: 0 other events
Deaths: 0 deaths

Placebo

Serious events: 24 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Alirocumab
n=57 participants at risk
alirocumab 150mg subcutaneous every other week for one year following start of study drug
Placebo
n=57 participants at risk
placebo to match alirocumab every other week for one year following start of study drug
Cardiac disorders
Elevated troponin
0.00%
0/57 • From randomization through 12 months follow-up
1.8%
1/57 • From randomization through 12 months follow-up
Cardiac disorders
Antibody mediated rejection
0.00%
0/57 • From randomization through 12 months follow-up
1.8%
1/57 • From randomization through 12 months follow-up
Respiratory, thoracic and mediastinal disorders
Hemoptysis
1.8%
1/57 • From randomization through 12 months follow-up
0.00%
0/57 • From randomization through 12 months follow-up
Infections and infestations
Coronavirus disease 2019
1.8%
1/57 • From randomization through 12 months follow-up
3.5%
2/57 • From randomization through 12 months follow-up
Nervous system disorders
Anxiety/panic attacks
0.00%
0/57 • From randomization through 12 months follow-up
1.8%
1/57 • From randomization through 12 months follow-up
Musculoskeletal and connective tissue disorders
Acute gout
1.8%
1/57 • From randomization through 12 months follow-up
0.00%
0/57 • From randomization through 12 months follow-up
Cardiac disorders
Intermittent supraventricular tachycardia
0.00%
0/57 • From randomization through 12 months follow-up
1.8%
1/57 • From randomization through 12 months follow-up
Cardiac disorders
Ventricular fibrillation cardiac arrest
1.8%
1/57 • From randomization through 12 months follow-up
0.00%
0/57 • From randomization through 12 months follow-up
Gastrointestinal disorders
Nausea, vomiting, and diarrhea
3.5%
2/57 • From randomization through 12 months follow-up
0.00%
0/57 • From randomization through 12 months follow-up
Immune system disorders
Tonsilitis
1.8%
1/57 • From randomization through 12 months follow-up
0.00%
0/57 • From randomization through 12 months follow-up
Immune system disorders
Neutropenic fever
1.8%
1/57 • From randomization through 12 months follow-up
0.00%
0/57 • From randomization through 12 months follow-up
Infections and infestations
Clostridioides difficile Gastroenteritis
1.8%
1/57 • From randomization through 12 months follow-up
0.00%
0/57 • From randomization through 12 months follow-up
Musculoskeletal and connective tissue disorders
Neck pain
0.00%
0/57 • From randomization through 12 months follow-up
1.8%
1/57 • From randomization through 12 months follow-up
Cardiac disorders
Atrial fibrillation
0.00%
0/57 • From randomization through 12 months follow-up
1.8%
1/57 • From randomization through 12 months follow-up
Respiratory, thoracic and mediastinal disorders
Shortness of breath
1.8%
1/57 • From randomization through 12 months follow-up
3.5%
2/57 • From randomization through 12 months follow-up
Cardiac disorders
Grade 2R moderate acute cellular rejection
0.00%
0/57 • From randomization through 12 months follow-up
1.8%
1/57 • From randomization through 12 months follow-up
Gastrointestinal disorders
Oropharyngeal ulcers
0.00%
0/57 • From randomization through 12 months follow-up
1.8%
1/57 • From randomization through 12 months follow-up
Infections and infestations
Pneumonia of right lower lobe due to infectious organism
0.00%
0/57 • From randomization through 12 months follow-up
1.8%
1/57 • From randomization through 12 months follow-up
Nervous system disorders
Hyponatremia
0.00%
0/57 • From randomization through 12 months follow-up
1.8%
1/57 • From randomization through 12 months follow-up
Infections and infestations
Toxoplasma gondii infection
0.00%
0/57 • From randomization through 12 months follow-up
1.8%
1/57 • From randomization through 12 months follow-up
Musculoskeletal and connective tissue disorders
Chest wall mass
1.8%
1/57 • From randomization through 12 months follow-up
0.00%
0/57 • From randomization through 12 months follow-up
Gastrointestinal disorders
Enteritis
1.8%
1/57 • From randomization through 12 months follow-up
0.00%
0/57 • From randomization through 12 months follow-up
Gastrointestinal disorders
Diverticulitis
0.00%
0/57 • From randomization through 12 months follow-up
1.8%
1/57 • From randomization through 12 months follow-up
Infections and infestations
Sternal incision infection
1.8%
1/57 • From randomization through 12 months follow-up
0.00%
0/57 • From randomization through 12 months follow-up
Surgical and medical procedures
Surgery: respiratory decompensation
0.00%
0/57 • From randomization through 12 months follow-up
1.8%
1/57 • From randomization through 12 months follow-up
Surgical and medical procedures
Percutaneous endoscopic gastrostomy
0.00%
0/57 • From randomization through 12 months follow-up
1.8%
1/57 • From randomization through 12 months follow-up
Infections and infestations
Sepsis
0.00%
0/57 • From randomization through 12 months follow-up
3.5%
2/57 • From randomization through 12 months follow-up
Immune system disorders
Post-Transplant Lymphoproliferative Disease
0.00%
0/57 • From randomization through 12 months follow-up
1.8%
1/57 • From randomization through 12 months follow-up
Infections and infestations
Community acquired pneumonia of left lower lobe of lung
1.8%
1/57 • From randomization through 12 months follow-up
0.00%
0/57 • From randomization through 12 months follow-up
Infections and infestations
Cytomegalovirus
3.5%
2/57 • From randomization through 12 months follow-up
0.00%
0/57 • From randomization through 12 months follow-up
Infections and infestations
Pneumonia
1.8%
1/57 • From randomization through 12 months follow-up
0.00%
0/57 • From randomization through 12 months follow-up
Infections and infestations
Norovirus
0.00%
0/57 • From randomization through 12 months follow-up
1.8%
1/57 • From randomization through 12 months follow-up
Nervous system disorders
Opioid withdrawal
0.00%
0/57 • From randomization through 12 months follow-up
1.8%
1/57 • From randomization through 12 months follow-up
Musculoskeletal and connective tissue disorders
Mechanical fall
0.00%
0/57 • From randomization through 12 months follow-up
1.8%
1/57 • From randomization through 12 months follow-up

Other adverse events

Adverse event data not reported

Additional Information

William Fearon, MD

Stanford University

Phone: (650) 725-2621

Results disclosure agreements

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