Efficacy and Safety Of Alirocumab to Prevent Early Cardiac Allograft Vasculopathy in Recent Heart Transplant Recipients

• Status: Recruiting
• Trial end date: 2023-02-01
• Target enrollment: 0
• Participant gender: All

Summary

Cardiac allograft vasculopathy (CAV) represents the leading cause of late morbidity and mortality in heart transplant recipients as the second most frequent cause of all deaths at 3 years. In distinction from general coronary atherosclerosis, CAV affects diffusely the entire coronary vasculature with marked intimal proliferation and concentric vascular thickening and fibrosis. It was demonstrated that most of the intimal thickening due to CAV occurs during the first year after transplantation. Furthermore, the severity of the CAV appears to correlate with lipid abnormalities and elevated low-density lipoprotein cholesterol (LDL-C) is very common after transplantation with nadir of LDL levels occurring at 6 months.

Because of drug-drug interactions, heart transplant recipients cannot be treated with adequate doses of statins to achieve desirable reduction of LDL-C levels (reduction ˂ 60% of LDL-C). The use of alternative lipid-lowering drugs including bile acid sequestrates, fibrates, nicotinic acid or ezetimibe is not recommended in post-transplant scenario. Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) increase availability has emerged as a novel drug tool for LDL-C lowering, capable to lower LDL-C by more than 60% even in statin-treated patients with very good safety profile.

Although heart transplant recipients fulfill approved indication and standard clinical guidelines of a PCSK9 inhibitor, alirocumab, there are no available data on use of PCSK9 inhibitor in post-transplant situation.

The purpose of the ACAV study is to clarify efficacy and safety of alirocumab compared to placebo administered during the first year after transplantation in heart transplant recipients in addition to background atorvastatin therapy. Except lipid profile, optical coherence tomography (OCT) will be performed as the objective efficacy endpoint to examine thickness and lumen of coronary vessels. It is expected that inhibition of PCSK9 in heart transplant recipient will dramatically improve post-transplant lipoprotein levels and perhaps slow down development of CAV in the most critical period of the first year after transplantation.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Institute for Clinical and Experimental Medicine
• Collaborators: Centre of Cardiovascular and Transplantation Surgery, Czech Republic; St. Anne's University Hospital Brno, Czech Republic
• Treatments: Antibodies, Monoclonal

Criteria

Inclusion Criteria:

1. New cardiac transplant recipient ≥ 18 years of age willing to participate in the study.

2. Ability to understand study procedures and to comply with them for the entire length of the study.

3. Written informed consent obtained from subject or subject's legal representative.

4. Heart transplantation surgery performed 3 - 8 weeks before the baseline visit.

Exclusion Criteria:

1. Known hypersensitivity/allergy reaction to study medication.

2. Complicated post-transplant outcome with poor neurological status, multiorgan failure or graft dysfunction.

3. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.

4. Lipoprotein apheresis is planned of performed.

5. Level of LDL-C ≥ 8 mmol/L at screening.

6. Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.

7. Participation in any other interventional study.

Known hypersensitivity/allergy to contrast agent or severe renal insufficiency (eGFR ˂ 30 mL/min/1.75 m2) exclude patient from OCT imaging only, not from the whole study.