Heart Transplant
Conditions
Keywords
coronary allograft vasculopathy, lipid, heart transplant, low density lipoprotein, proprotein convertase subtilisin/kexin type 9, PCSK9
Brief summary
Coronary allograft vasculopathy (CAV) is diffusely accelerated atherosclerosis of a transplanted heart. Evolocumab (Repatha) is an FDA-approved drug for lowering low density lipoprotein (LDL) in patients who have not received a heart transplant. This drug works as a PCSK9-inhibitor. The primary objective of this study is to measure the impact of PCSK9-inhibitors on serum LDL in heart transplant patients with CAV after 12 weeks compared to baseline.
Detailed description
Heart transplant remains the treatment of choice for patients with advanced heart failure. Coronary allograft vasculopathy (CAV) is diffusely accelerated atherosclerosis of the donor heart, and limits long term survival after transplant. The pathophysiology of CAV is complex and involves smooth muscle proliferation, inflammatory infiltrates, and lipid deposition. To date, only statin therapy has reduced CAV-related mortality. PCSK9 inhibitors are a new lipid lowering therapy shown to reduce cardiovascular clinical events in patients with coronary artery disease. We hypothesize that PCSK9 inhibition via evolocumab will significantly lower low density lipoprotein (LDL) and be well-tolerated in transplant patients with CAV. This phase II, open label, single center trial with enroll up to 40 heart transplant patients with CAV for treatment with evolocumab for one year. The primary outcome will be percent change in LDL at 12 weeks. Secondary outcomes will include change in CAV progression, impact of evolocumab on immunosuppression regimens and transplant rejection, and change in serum lipids after 52 weeks. Results of this study are intended to provide safety data in heart transplant patients with CAV and assess secondary outcomes including CAV progression and impact on immunosuppression and transplant rejection.
Interventions
DRUGEvolocumab
Enrolled study participants will be treated with evolocumab (Repatha) 140 mg injected subcutaneously every 2 weeks for 52 weeks. All study participants will receive instruction on correct self-administration by research pharmacists. Study drug will be mailed to patients on a monthly basis for self-administration by patients. The evolocumab dose (140 mg every 2 weeks) will remain constant for the duration of the study. Side effects will be assessed on a quarterly basis. Serious adverse events considered related to treatment, death, and pregnancy will all result in immediate discontinuation of the study drug.
Sponsors
Amgen
University of Nebraska
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Heart transplant patients 19-80 years of age * Coronary allograft vasculopathy grade 1 or 2 documented by left heart cardiac catheterization * Able to provide signed informed consent
Exclusion criteria
* Cardiac allograft vasculopathy (CAV) grade 3 * Rejection requiring IV therapy in the prior 3 months * Infection requiring IV therapy in the prior 3 months * Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3 times the upper limit of normal * Current or recent use of a PCSK9 inhibitor within the past 12 weeks * Organ transplant recipient other than heart * Renal dysfunction defined as glomerular filtration rate (GFR) \< 20 ml/min * Known allergy to evolocumab or its components
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Serum LDL (mg/dL) After 12 Weeks of Evolocumab | 12 weeks | The primary outcome measure for this study was percent change in LDL from baseline after 12 weeks of evolocumab therapy. Serum LDL was measured at baseline and after 12 weeks of evolocumab therapy. This primary endpoint was used in prior phase 2 trials investigating evolocumab in other patient populations. Wilcoxon matched-pairs signed rank test was used for statistical assessment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Evolocumab Heart transplant participants with CAV who received the study drug. Enrolled study participants will be treated with evolocumab (Repatha) 140 mg injected subcutaneously every 2 weeks for 52 weeks. | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
Baseline characteristics
| Characteristic | Evolocumab |
|---|---|
| Age, Continuous | 63 years |
| Low density lipoprotein (LDL) | 100 mg/dL |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 26 |
| other Total, other adverse events | 16 / 26 |
| serious Total, serious adverse events | 11 / 26 |
Outcome results
Primary
Percent Change in Serum LDL (mg/dL) After 12 Weeks of Evolocumab
The primary outcome measure for this study was percent change in LDL from baseline after 12 weeks of evolocumab therapy. Serum LDL was measured at baseline and after 12 weeks of evolocumab therapy. This primary endpoint was used in prior phase 2 trials investigating evolocumab in other patient populations. Wilcoxon matched-pairs signed rank test was used for statistical assessment.
Time frame: 12 weeks
Population: This single arm study investigated the impact of PCSK9 inhibition via evolocumab on serum LDL in heart transplant patients with CAV after 12 weeks compared to baseline. Percent Change in serum LDL will serve as the primary endpoint for comparison.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Evolocumab | Percent Change in Serum LDL (mg/dL) After 12 Weeks of Evolocumab | 68 percent change |