Cardiac Allograft VasculopathyPhase 4ACAVNCT04193306
Efficacy and Safety Of Alirocumab to Prevent Early Cardiac Allograft Vasculopathy in Recent Heart Transplant Recipients
A Phase 4 study testing Alirocumab in people with Cardiac Allograft Vasculopathy, run by Institute for Clinical and Experimental Medicine at 1 site in Czechia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Allograft Vasculopathy
- What is being tested?
- Alirocumab
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 126 participants
- Where
- 1 siteCzechia
- Study dates
- 18 Nov 2019to Jul 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Lenka Hoskova, MD, PhD contact
Czechia1 site, 1 recruiting
- Recruiting
Institute for Clinical and Experimental Medicine
Prague
Vojtech Melenovsky, doc. MUDr. PhD
About this study
Official title: 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.
Read more
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.
Read the detailed description
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.
- Conditions
- Cardiac Allograft Vasculopathy
- Being tested
- Alirocumab, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlirocumabDrug
Alirocumab 150 mg s.c. every 2 weeks
PlaceboOther
Placebo s.c. every 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| Alirocumab | Experimental | alirocumab 150 mg s.c. every 2 weeks, for 48 weeks Receives: Drug: Alirocumab |
| Placebo | Placebo comparator | placebo s.c. every 2 weeks, for 48 weeks Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
calculated LDL cholesterol concentration
the difference in mean of values from visits 2,3,4,5 and 6 between alirocumab/placebo arms
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: the time period between 2 and 12 months after heart transplantation
Secondary outcomes (8)
calculated LDL cholesterol concentration
Percent change from baseline (visit 1) to visit 6 between alirocumab/placebo arms
Measured: between 1 and 12 months after heart transplantation
calculated LDL cholesterol concentration
Difference in values at every study visit between alirocumab/placebo arms
Measured: between 1 and 12 months after heart transplantation
lipid parameters values
Difference in values at every study visit between alirocumab/placebo arms
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 1 and 12 months after heart transplantation
incidence of adverse events
Assessment of safety of alirocumab in comparison to placebo
Measured: 1 and 15 months after heart transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2019
- Study start18 Nov 2019
- Primary completionMay 2025 (estimated)
- Study completionJul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cardiac Allograft VasculopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 126 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institute for Clinical and Experimental Medicine
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Vojtech Melenovsky, MD, PhD, Institute for Clinical and Experimental Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04193306
- Sponsor's protocol ID
- ACAV2018
- Acronym
- ACAV
- Status last verified
- Sep 2023
- First submitted
- 26 Nov 2019
- Last updated
- 3 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 30253306Pazdernik 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.
PubMed 29706574
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ACAV: Efficacy and Safety Of Alirocumab to Prevent Early Cardiac Allograft Vasculopathy in Recent Heart Transplant Recipients
- ClinicalTrials.gov ID
- NCT04193306
- Acronym / sponsor ID
- ACAV / ACAV2018
- Conditions
- Cardiac Allograft Vasculopathy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 126 participants (estimated)
- Lead sponsor
- Institute for Clinical and Experimental MedicineOther government
- Study start
- 18 Nov 2019 (actual)
- Primary completion
- May 2025 (estimated)
- Study completion
- Jul 2025 (estimated)
- First posted
- 10 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Alirocumab | Experimental | Drug: Alirocumabalirocumab 150 mg s.c. every 2 weeks, for 48 weeks |
| Placebo | Placebo comparator | Other: Placeboplacebo s.c. every 2 weeks, for 48 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlirocumabAlirocumab 150 mg s.c. every 2 weeks | Drug | Alirocumab |
| PlaceboPlacebo s.c. every 2 weeks | Other | Placebo |
Primary outcome
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
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
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
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
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
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
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
8 secondary outcomes
calculated LDL cholesterol concentration
Time frame: between 1 and 12 months after heart transplantation
calculated LDL cholesterol concentration
Time frame: between 1 and 12 months after heart transplantation
lipid parameters values
Time frame: between 1 and 12 months after heart transplantation
calculated LDL cholesterol concentration
Time frame: between 12 and 15 months after heart transplantation
lipid parameters values
Time frame: between 12 and 15 months after heart transplantation
mean intimal thickness assessed by OCT
Time frame: 1 and 12 months after heart transplantation
mean lumen volume assessed by OCT
Time frame: 1 and 12 months after heart transplantation
incidence of adverse events
Time frame: 1 and 15 months after heart transplantation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2023.
- Background: PubMed 30253306Chen 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.
- Background: PubMed 29706574Pazdernik 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lenka Hoskova, MD, PhD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Alirocumab in people with Cardiac Allograft Vasculopathy, run by Institute for Clinical and Experimental Medicine at 1 site in Czechia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Vojtech Melenovsky, MD, PhD (420 739 528 029, vojtech.melenovsky@ikem.cz), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
calculated LDL cholesterol concentration (time frame: the time period between 2 and 12 months after heart transplantation). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04193306, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2023.