Vasculopathy
Conditions
Keywords
Heart Transplant
Brief summary
The focus of this study is to test the safety and efficacy of the PCSK9 inhibitor, alirocumab when administered early after heart transplantation (HT).The main objective of this project is to test the safety and impact on cardiac allograft vasculopathy (CAV) of alirocumab when given early after HT.
Interventions
BIOLOGICALalirocumab
alirocumab 150mg Subcutaneous
BIOLOGICALplacebo
placebo to match alirocumab
Sponsors
Stanford University
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Heart Transplant recipient
Exclusion criteria
* impaired liver function
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plaque Volume | Baseline to one year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Low-Density Lipoprotein Cholesterol (LDL-C) Levels | Baseline and one year | 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). |
| Apolipoprotein B (ApoB) | Baseline and 1 year | 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. |
| Lipoprotein(a) | Baseline and 1 year | Lipoprotein(a) was measured at baseline and 1 year to assess the efficacy of alirocumab in lowering this specific lipid parameter. |
| Total Cholesterol | Baseline and one year | Total cholesterol was measured to assess the efficacy of alirocumab versus placebo on overall impact for this specific lipid parameter. |
| HDL Cholesterol | Baseline and one year | HDL cholesterol was measured to assess the efficacy of alirocumab versus placebo on overall impact for this specific lipid parameter. |
| Triglycerides | Baseline and one year | Triglycerides were measured to assess the efficacy of alirocumab versus placebo on overall impact for this specific lipid parameter. |
| High-sensitivity C-reactive Protein (Hs-CRP) | Baseline and one year | hs-CRP was measured to assess the efficacy of alirocumab versus placebo on overall impact for this specific lipid parameter |
| Fractional Flow Reserve (FFR) | baseline and one year | 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. |
| Coronary Flow Reserve (CFR) | Baseline and 1 year | 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. |
| Index of Microcirculatory Resistance (IMR) | Baseline and 1 year | 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. |
| Lipid Core Burden Index (LCBI) | Baseline and 1 year | 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. |
| Maximum Lipid Core Burden Index in 4 mm (maxLCBI 4mm) | Baseline and 1 year | 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). |
| Maximum Intimal Thickness (MIT) | Baseline and 1 year | Measured using intravascular ultrasound (IVUS), this represents the thickness of the innermost layer of the artery wall at its thickest point. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORWilliam F Fearon, MD
Stanford University
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 53.3 years STANDARD_DEVIATION 14 |
| Comorbidities CMV IgG positive | 70 Participants |
| Comorbidities Diabetes | 27 Participants |
| Comorbidities Hypercholesterolemia | 37 Participants |
| Comorbidities Hypertension | 45 Participants |
| Comorbidities Ischemic cardiomyopathy | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 47 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 13 Participants |
| Race (NIH/OMB) White | 31 Participants |
| Region of Enrollment United States | 114 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 57 | 0 / 57 |
| other Total, other adverse events | 0 / 57 | 0 / 57 |
| serious Total, serious adverse events | 17 / 57 | 24 / 57 |
Outcome results
None listed