- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04193306
Efficacy and Safety Of Alirocumab to Prevent Early Cardiac Allograft Vasculopathy in Recent Heart Transplant Recipients (ACAV)
ACAV: Efficacy and Safety Of Alirocumab to Prevent Early Cardiac Allograft Vasculopathy in Recent Heart Transplant Recipients
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Vojtech Melenovsky, MD, PhD
- Phone Number: 420 739 528 029
- Email: vojtech.melenovsky@ikem.cz
Study Contact Backup
- Name: Lenka Hoskova, MD, PhD
- Email: lenka.hoskova@ikem.cz
Study Locations
-
-
-
Prague, Czechia
- Recruiting
- Institute for Clinical and Experimental Medicine
-
Contact:
- Vojtech Melenovsky, doc. MUDr. PhD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- New cardiac transplant recipient ≥ 18 years of age willing to participate in the study.
- Ability to understand study procedures and to comply with them for the entire length of the study.
- Written informed consent obtained from subject or subject's legal representative.
- Heart transplantation surgery performed 3 - 8 weeks before the baseline visit.
Exclusion Criteria:
- Known hypersensitivity/allergy reaction to study medication.
- Complicated post-transplant outcome with poor neurological status, multiorgan failure or graft dysfunction.
- 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.
- Lipoprotein apheresis is planned of performed.
- Level of LDL-C ≥ 8 mmol/L at screening.
- Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Alirocumab
alirocumab 150 mg s.c.
every 2 weeks, for 48 weeks
|
Alirocumab 150 mg s.c.
every 2 weeks
|
Placebo Comparator: Placebo
placebo s.c.
every 2 weeks, for 48 weeks
|
Placebo s.c. every 2 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
calculated LDL cholesterol concentration
Time Frame: the time period between 2 and 12 months after heart transplantation
|
the difference in mean of values from visits 2,3,4,5 and 6 between alirocumab/placebo arms
|
the time period between 2 and 12 months after heart transplantation
|
HDL cholesterol concentration
Time Frame: the time period between 2 and 12 months after heart transplantation
|
the difference in mean of values from visits 2,3,4,5 and 6 between alirocumab/placebo arms
|
the time period between 2 and 12 months after heart transplantation
|
total cholesterol
Time Frame: the time period between 2 and 12 months after heart transplantation
|
the difference in mean of values from visits 2,3,4,5 and 6 between alirocumab/placebo arms
|
the time period between 2 and 12 months after heart transplantation
|
triglycerides
Time Frame: the time period between 2 and 12 months after heart transplantation
|
the difference in mean of values from visits 2,3,4,5 and 6 between alirocumab/placebo arms
|
the time period between 2 and 12 months after heart transplantation
|
ApoB
Time Frame: the time period between 2 and 12 months after heart transplantation
|
the difference in mean of values from visits 2,3,4,5 and 6 between alirocumab/placebo arms
|
the time period between 2 and 12 months after heart transplantation
|
Lp (a)
Time Frame: the time period between 2 and 12 months after heart transplantation
|
the difference in mean of values from visits 2,3,4,5 and 6 between alirocumab/placebo arms
|
the time period between 2 and 12 months after heart transplantation
|
Apo A1
Time Frame: the time period between 2 and 12 months after heart transplantation
|
the difference in mean of values from visits 2, 3, 4 ,5 and 6 between alirocumab/placebo arms
|
the time period between 2 and 12 months after heart transplantation
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
calculated LDL cholesterol concentration
Time Frame: between 1 and 12 months after heart transplantation
|
Percent change from baseline (visit 1) to visit 6 between alirocumab/placebo arms
|
between 1 and 12 months after heart transplantation
|
calculated LDL cholesterol concentration
Time Frame: between 1 and 12 months after heart transplantation
|
Difference in values at every study visit between alirocumab/placebo arms
|
between 1 and 12 months after heart transplantation
|
lipid parameters values
Time Frame: between 1 and 12 months after heart transplantation
|
Difference in values at every study visit between alirocumab/placebo arms
|
between 1 and 12 months after heart transplantation
|
calculated LDL cholesterol concentration
Time Frame: between 12 and 15 months after heart transplantation
|
Difference in values at visit 6 compared to visit 7 between alirocumab/placebo arms
|
between 12 and 15 months after heart transplantation
|
lipid parameters values
Time Frame: between 12 and 15 months after heart transplantation
|
Difference in values at visit 6 compared to visit 7 between alirocumab/placebo arms
|
between 12 and 15 months after heart transplantation
|
mean intimal thickness assessed by OCT
Time Frame: 1 and 12 months after heart transplantation
|
Percent change from baseline (visit 1) to visit 6 between alirocumab/placebo arms
|
1 and 12 months after heart transplantation
|
mean lumen volume assessed by OCT
Time Frame: 1 and 12 months after heart transplantation
|
Percent change from baseline (visit 1) to visit 6 between alirocumab/placebo arms
|
1 and 12 months after heart transplantation
|
incidence of adverse events
Time Frame: 1 and 15 months after heart transplantation
|
Assessment of safety of alirocumab in comparison to placebo
|
1 and 15 months after heart transplantation
|
Collaborators and Investigators
Publications and helpful links
General Publications
- Chen Z, Pazdernik M, Zhang H, Wahle A, Guo Z, Bedanova H, Kautzner J, Melenovsky V, Kovarnik T, Sonka M. Quantitative 3D Analysis of Coronary Wall Morphology in Heart Transplant Patients: OCT-Assessed Cardiac Allograft Vasculopathy Progression. Med Image Anal. 2018 Dec;50:95-105. doi: 10.1016/j.media.2018.09.003. Epub 2018 Sep 14.
- Pazdernik M, Chen Z, Bedanova H, Kautzner J, Melenovsky V, Karmazin V, Malek I, Tomasek A, Ozabalova E, Krejci J, Franekova J, Wahle A, Zhang H, Kovarnik T, Sonka M. Early detection of cardiac allograft vasculopathy using highly automated 3-dimensional optical coherence tomography analysis. J Heart Lung Transplant. 2018 Aug;37(8):992-1000. doi: 10.1016/j.healun.2018.04.002. Epub 2018 Apr 6.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ACAV2018
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cardiac Allograft Vasculopathy
-
Universita di VeronaCompletedCardiac Allograft VasculopathyItaly, Netherlands
-
University of MinnesotaWithdrawnCardiac Allograft VasculopathyUnited States
-
University of MinnesotaWithdrawnCardiac Allograft VasculopathyUnited States
-
Assistance Publique Hopitaux De MarseilleUnknownCardiac Allograft VasculopathyFrance
-
Samsung Medical CenterRecruitingCardiac Allograft VasculopathyKorea, Republic of
-
Mayo ClinicUniversity of CalgaryCompletedCardiac Allograft VasculopathyUnited States
-
Cedars-Sinai Medical CenterGenzyme, a Sanofi CompanyWithdrawn
-
Stanford UniversityCedars-Sinai Medical Center; VA Palo Alto Health Care SystemCompletedCardiac Allograft VasculopathyUnited States
-
University of MinnesotaWithdrawnCardiac Allograft VasculopathyUnited States
-
University of MinnesotaWithdrawn
Clinical Trials on Alirocumab
-
Fundación Hipercolesterolemia FamiliarCompletedFamilial HypercholesterolemiaSpain
-
Westside Medical Associates of Los AngelesRegeneron Pharmaceuticals; University of WashingtonUnknownAtherosclerosis | HyperlipidemiaUnited States
-
Population Health Research InstituteCompletedST Elevation Myocardial Infarction | Dyslipidemias | Hypercholesterolemia | Hyperlipidemias | Acute Coronary Syndrome | Physiological Effects of DrugsCanada
-
Shanghai Tong Ren HospitalChina Cardiovascular AssociationRecruitingAcute Myocardial InfarctionChina
-
Regeneron PharmaceuticalsSanofiCompletedHypercholesterolemiaUnited States, Bulgaria, Chile, Estonia, Japan, Mexico, Russian Federation, South Africa, Ukraine
-
University of VirginiaNorthwestern UniversityCompletedPeripheral Arterial DiseaseUnited States
-
Regeneron PharmaceuticalsSanofiTerminatedHeterozygous Familial Hypercholesterolemia | Non-familial HypercholesterolemiaUnited States, Bulgaria, Estonia, Russian Federation, South Africa, Ukraine
-
Washington University School of MedicineCompleted
-
University Hospital Inselspital, BerneRegeneron PharmaceuticalsCompletedCoronary Circulation | Atheroma; Myocardial | Coronary VesselDenmark, Switzerland, Austria, Netherlands
-
Regeneron PharmaceuticalsSanofiCompletedHeterozygous Familial HypercholesterolemiaUnited States, Germany