Heart TransplantPhase 2NCT03944577
Impact of Evolocumab in Cardiac Transplant Patients With CAV
A Phase 2 study testing Evolocumab in people with Heart Transplant, run by University of Nebraska at 1 site in United States.
Trial summary
Coronary allograft vasculopathy (CAV) is diffusely accelerated atherosclerosis of a transplanted heart. Evolocumab (Repatha) is an FDA-approved drug for lowering low density lipoprotein (LDL) in patients who have not received a heart transplant. This drug works as a PCSK9-inhibitor. Read more about this study
- Who is it for?
- Ages 19 to 80 years
- Conditions the study is for
- Heart Transplant
- What is being tested?
- Evolocumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jul 2019to 28 Mar 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 19 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Cardiac allograft vasculopathy (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 glomerular filtration rate (GFR) < 20 ml/min
- Known allergy to evolocumab or its components
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Nebraska Medical Center
Omaha, Nebraska, 68198
About this study
Official title: Impact of Evolocumab (Repatha) in Cardiac Transplant Patients With Coronary Allograft Vasculopathy
Coronary allograft vasculopathy (CAV) is diffusely accelerated atherosclerosis of a transplanted heart. Evolocumab (Repatha) is an FDA-approved drug for lowering low density lipoprotein (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.
Read the 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 low density lipoprotein (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.
- Conditions
- Heart Transplant
- Being tested
- Evolocumab
- Keywords
- coronary allograft vasculopathy, lipid, heart transplant, low density lipoprotein, proprotein convertase subtilisin/kexin type 9, PCSK9
- Medical subject headings
- Hypercholesterolemia, Autosomal Dominant, 3
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EvolocumabDrug
Also called 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.
| Study group | Role | What they receive |
|---|---|---|
| Evolocumab | Experimental | Patients who will receive the study drug. Receives: Drug: Evolocumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Serum LDL (mg/dL) After 12 Weeks of Evolocumab
The primary outcome measure for this study was percent change in LDL from baseline after 12 weeks of evolocumab therapy. Serum LDL was measured at baseline and after 12 weeks of evolocumab therapy. This primary endpoint was used in prior phase 2 trials investigating evolocumab in other patient populations. Wilcoxon matched-pairs signed rank test was used for statistical assessment.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2019
- Study start15 Jul 2019
- Primary completion28 Mar 2023
- Study completion28 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Heart TransplantStudies of the same condition, open and under way.
- More trials run by University of NebraskaThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Sponsor
- Investigators
- Douglas A Stoller, MD, PhD, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03944577
- Sponsor's protocol ID
- 0104-19-FB
- Status last verified
- May 2024
- First submitted
- 22 Apr 2019
- Last updated
- 3 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: There is not a plan to make individual participant data (IPD) available) to other researchers.
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Evolocumab (Repatha) in Cardiac Transplant Patients With Coronary Allograft Vasculopathy
- ClinicalTrials.gov ID
- NCT03944577
- Acronym / sponsor ID
- 0104-19-FB
- Conditions
- Heart Transplant
- Keywords
- coronary allograft vasculopathy, lipid, heart transplant, low density lipoprotein, proprotein convertase subtilisin/kexin type 9, PCSK9
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- 15 Jul 2019 (actual)
- Primary completion
- 28 Mar 2023 (actual)
- Study completion
- 28 Mar 2023 (actual)
- First posted
- 9 May 2019 (actual)
- Results
- Posted 3 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Coronary allograft vasculopathy (CAV) is diffusely accelerated atherosclerosis of a transplanted heart. Evolocumab (Repatha) is an FDA-approved drug for lowering low density lipoprotein (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.
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 low density lipoprotein (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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Evolocumab | Experimental | Drug: EvolocumabPatients who will receive the study drug. |
Who may qualify
- Ages
- 19 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (8 listed)
- Cardiac allograft vasculopathy (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
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 |
|---|---|---|
| EvolocumabAlso: RepathaEnrolled 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. | Drug | Evolocumab |
Primary outcome
Percent Change in Serum LDL (mg/dL) After 12 Weeks of Evolocumab
Time frame: 12 weeks
The primary outcome measure for this study was percent change in LDL from baseline after 12 weeks of evolocumab therapy. Serum LDL was measured at baseline and after 12 weeks of evolocumab therapy. This primary endpoint was used in prior phase 2 trials investigating evolocumab in other patient populations. Wilcoxon matched-pairs signed rank test was used for statistical assessment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. There is not a plan to make individual participant data (IPD) available) to other researchers.
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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.
Douglas A Stoller, MD, PhD principal investigator
University of Nebraska
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Evolocumab in people with Heart Transplant, run by University of Nebraska at 1 site in United States.
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 3 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: finished, as of the sponsor's last update on 3 Jun 2024. 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 United States. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change in Serum LDL (mg/dL) After 12 Weeks of Evolocumab (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Jun 2024.