A Phase 4 interventional study of Alirocumab and Placebo in Cardiac Allograft Vasculopathy, sponsored by Institute for Clinical and Experimental Medicine. Recruiting at 1 site in Czechia. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-10-03.
Sponsored by Institute for Clinical and Experimental Medicine · Phase 4, Interventional, and Treatment
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.
This is a double-blind, placebo-controlled, randomized, prospective, phase IV trial with parallel design. 126 of new cardiac transplant recipients are planned to be enrolled in two sites: 1) Transplant Centre at Institute for Clinical and Experimental Medicine, Prague, Czech Republic, and 2) St Anne's University Hospital (FNUSA) - Centre of Cardiovascular and Transplant Surgery (CKTCH) in Brno, Czech Republic. Screening data will be reviewed to determine subject eligibility. Subjects who meet all inclusion criteria and none of the exclusion criteria will be entered into the study. Screening period could last up to four weeks. Subjects will be randomized 1:1 to receive either alirocumab 150 mg every 2 weeks or placebo between month 1 and month 12 after transplantation (study treatment will start after the first surveillance cardiac catheterization approximately one month after heart transplantation and it will be completed after the second surveillance cardiac catheterization approximately 12 months after heart transplantation). Furthermore, all subjects will be on a background statin treatment with atorvastatin 10 mg daily. After Screening and Baseline visit, 5 visits are planned during the treatment period (4, 8, 20, 34 and 48 weeks after baseline) and follow-up visit is planned 60 weeks after baseline. Maximal expected duration of subject participation will be 15 months.
1,027 studies on the registry are indexed under Vascular Diseases; 167 are open to participants now.
This study's planned enrollment of 126 is above the median of 78 across 639 interventional studies indexed under Vascular Diseases.
Browse Vascular Diseases studies →Institute for Clinical and Experimental Medicine is the lead sponsor of 60 studies on the registry; 20 are open to participants now.
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Exclusion Criteria:
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.
alirocumab 150 mg s.c. every 2 weeks, for 48 weeks
Drug: Alirocumab
placebo s.c. every 2 weeks, for 48 weeks
Other: Placebo
Alirocumab 150 mg s.c. every 2 weeks
Placebo s.c. every 2 weeks
calculated LDL cholesterol concentration
the difference in mean of values from visits 2,3,4,5 and 6 between alirocumab/placebo arms
Time frame: the time period between 2 and 12 months after heart transplantation
HDL cholesterol concentration
the difference in mean of values from visits 2,3,4,5 and 6 between alirocumab/placebo arms
Time frame: the time period between 2 and 12 months after heart transplantation
total cholesterol
the difference in mean of values from visits 2,3,4,5 and 6 between alirocumab/placebo arms
Time frame: the time period between 2 and 12 months after heart transplantation
triglycerides
the difference in mean of values from visits 2,3,4,5 and 6 between alirocumab/placebo arms
Time frame: the time period between 2 and 12 months after heart transplantation
ApoB
the difference in mean of values from visits 2,3,4,5 and 6 between alirocumab/placebo arms
Time frame: the time period between 2 and 12 months after heart transplantation
Lp (a)
the difference in mean of values from visits 2,3,4,5 and 6 between alirocumab/placebo arms
Time frame: the time period between 2 and 12 months after heart transplantation
Apo A1
the difference in mean of values from visits 2, 3, 4 ,5 and 6 between alirocumab/placebo arms
Time frame: the time period between 2 and 12 months after heart transplantation
calculated LDL cholesterol concentration
Percent change from baseline (visit 1) to visit 6 between alirocumab/placebo arms
Time frame: between 1 and 12 months after heart transplantation
calculated LDL cholesterol concentration
Difference in values at every study visit between alirocumab/placebo arms
Time frame: between 1 and 12 months after heart transplantation
lipid parameters values
Difference in values at every study visit between alirocumab/placebo arms
Time frame: between 1 and 12 months after heart transplantation
calculated LDL cholesterol concentration
Difference in values at visit 6 compared to visit 7 between alirocumab/placebo arms
Time frame: between 12 and 15 months after heart transplantation
lipid parameters values
Difference in values at visit 6 compared to visit 7 between alirocumab/placebo arms
Time frame: between 12 and 15 months after heart transplantation
mean intimal thickness assessed by OCT
Percent change from baseline (visit 1) to visit 6 between alirocumab/placebo arms
Time frame: 1 and 12 months after heart transplantation
mean lumen volume assessed by OCT
Percent change from baseline (visit 1) to visit 6 between alirocumab/placebo arms
Time frame: 1 and 12 months after heart transplantation
incidence of adverse events
Assessment of safety of alirocumab in comparison to placebo
Time frame: 1 and 15 months after heart transplantation
Plan to share: No
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Institute for Clinical and Experimental Medicine