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Impact of Evolocumab in Cardiac Transplant Patients With CAV

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ClinicalTrials.gov Identifier: NCT03944577
Recruitment Status : Recruiting
First Posted : May 9, 2019
Last Update Posted : November 4, 2020
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Douglas Stoller, University of Nebraska

Brief Summary:
Coronary allograft vasculopathy (CAV) is diffusely accelerated atherosclerosis of a transplanted heart. Evolocumab (repatha) is an FDA-approved drug for lowering 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.

Condition or disease Intervention/treatment Phase
Heart Transplant Drug: Evolocumab (Repatha) Phase 2

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 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Impact of Evolocumab (Repatha) in Cardiac Transplant Patients With Coronary Allograft Vasculopathy
Actual Study Start Date : July 15, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : March 1, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Evolocumab

Arm Intervention/treatment
Experimental: Treatment Arm
Patients who will receive the study drug.
Drug: Evolocumab (Repatha)
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.




Primary Outcome Measures :
  1. To measure the effect of evolocumab on serum LDL as measured in mL/dL after 12 weeks of therapy in heart transplant patients. [ Time Frame: 12 weeks ]
    The primary objective of this study is to measure in the impact of PCSK9 inhibition via evolocumab on serum LDL in heart transplant patients with CAV after 12 weeks compared to baseline. Change in serum LDL will serve as the primary endpoint for comparison.



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Ages Eligible for Study:   19 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

  • 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 GFR < 20 ml/min
  • Known allergy to evolocumab or its components

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03944577


Locations
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United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
Contact: Douglas Stoller, MD, PhD    402-559-1350    douglas.stoller@unmc.edu   
Sponsors and Collaborators
University of Nebraska
Amgen
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Responsible Party: Douglas Stoller, Principal Investigator, University of Nebraska
ClinicalTrials.gov Identifier: NCT03944577    
Other Study ID Numbers: 20177584
First Posted: May 9, 2019    Key Record Dates
Last Update Posted: November 4, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is not a plan to make individual participant data (IPD) available) to other researchers.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Douglas Stoller, University of Nebraska:
coronary allograft vasculopathy
lipid
heart transplant
Additional relevant MeSH terms:
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Evolocumab
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents