Clinical trial NCT03944577: Impact of Evolocumab in Cardiac Transplant Patients With CAV
Official title: Impact of Evolocumab (Repatha) in Cardiac Transplant Patients With Coronary Allograft Vasculopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Transplant
Keywords: coronary allograft vasculopathy
lipid
heart transplant
low density lipoprotein
proprotein convertase subtilisin/kexin type 9
PCSK9
Lead sponsor: University of Nebraska
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2019-05-09
Enrollment: 26
Sex: ALL
Minimum age (years): 19
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percent Change in Serum LDL (mg/dL) After 12 Weeks of Evolocumab
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: Douglas A Stoller, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: