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Trial record 2 of 119 for:    EMPOWER CAD
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The Impact of Pcsk-9 Inhibition on PET CFR in Patients at High CV Risk (EMPOWER)

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ClinicalTrials.gov Identifier: NCT05152888
Recruitment Status : Recruiting
First Posted : December 10, 2021
Last Update Posted : June 22, 2023
Sponsor:
Information provided by (Responsible Party):
Marcelo F. Di Carli, MD, FACC, Brigham and Women's Hospital

Study Description
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Brief Summary:
The study protocol is a single-arm, open label pilot study designed to evaluate the impact of PCSK-9 inhibition on coronary blood flow in patients with stable coronary artery disease. Patients with stable coronary artery disease will be recruited from the BWH Cardiovascular Medicine clinic and/or from the BWH Nuclear Cardiology Laboratory. A target sample size of 50 participants will undergo imaging with N-13 ammonia or Rubidium-82 positron emission tomography (PET) and coronary computed tomography angiography (CCTA) before and after 12 months of PCSK-9 inhibition with Evolocumab to assess changes in myocardial blood flow, and plaque volume. To help account for physiological changes that may occur in myocardial blood flow and inflammatory biomarkers during the study period, we will also recruit a parallel control group of stable CAD patients who will undergo similar baseline and 12-month imaging and biomarker assessment. We plan to recruit 15 patients in the parallel control group.

Condition or disease Intervention/treatment Phase
Stable Coronary Disease Drug: Evolocumab Phase 4

Detailed Description:

The investigators propose an open-label investigator-initiated trial to directly test whether PCSK-9 inhibition with Evolocumab in patients with stable CAD improves PET CFR and stress MBF. To further elucidate the possible mechanisms by which myocardial blood flow improves with PCSK-9 inhibition, the investigators will assess changes in inflammatory biomarkers. The findings of this translational study will provide a physiological read-out of the comprehensive effects of Evolocumab on tissue perfusion and microvascular function in a high-risk population. As such, these data would serve to provide a mechanistic explanation for why Evolocumab may reduce cardiovascular events beyond a reduction in plaque burden and composition.

The central hypothesis of this study is that PCSK-9 inhibition will quantitatively improve myocardial blood flow as measured by positron emission tomography (PET) in patients with stable coronary artery disease. The investigators postulate that the improvement in myocardial blood flow will correlate with a reduction in inflammatory biomarkers, and not simply an improvement in coronary epicardial plaque burden.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The study protocol is an open label pilot study with a parallel control group.
Masking: None (Open Label)
Primary Purpose: Other
Official Title: The Impact of Pcsk-9 Inhibition on PET Coronary Flow Reserve in Patients at High Cardiovascular Risk (EMPOWER Study)
Actual Study Start Date : March 3, 2022
Estimated Primary Completion Date : December 31, 2025
Estimated Study Completion Date : December 31, 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Evolocumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Evolocumab
Informed consent will be obtained from study participants willing to participate in EMPOWER. Study participants will then undergo the baseline rest/stress cardiac PET scan along with CCTA. The final PET scan and CCTA will occur at 12 months after the intervention.
 Drug: Evolocumab
Evolocumab is a human monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9). Evolocumab was FDA approved in 2015 for the treatment of hyperlipidemia and subsequently approved in 2017 for the prevention of stroke and heart attack. 140mg single use SureClick autoinjector that is administered subcutaneously once every 2 weeks.
Other Name: Repatha
No Intervention: Control
Informed consent will be obtained from study participants willing to participate in EMPOWER. Study participants will then undergo the baseline rest/stress cardiac PET scan along with CCTA. The final PET scan and CCTA will occur at 12 months after the baseline.


Outcome Measures
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Primary Outcome Measures :
  1. Coronary Flow Reserve [ Time Frame: Change (from baseline) in global CFR, as measured by PET imaging at 52 weeks after initiation of Evolocumab therapy. ]
    Change in global coronary flow reserve (CFR) after 12 months of therapy with Evolocumab

  2. Stress Myocardial Blood Flow (MBF) [ Time Frame: Change (from baseline) in stress MBF, as measured by PET imaging at 52 weeks after initiation of Evolocumab therapy. ]
    Change in stress Myocardial Blood Flow (MBF) after 12 months of therapy with Evolocumab


Secondary Outcome Measures :
  1. Total Perfusion Deficit (TPD) [ Time Frame: Change (from baseline) in TPD, as measured by PET imaging at 52 weeks after initiation of Evolocumab therapy. ]
    Change in Total Perfusion Deficit (TPD) after 12 months of therapy with Evolocumab


Eligibility Criteria
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Ages Eligible for Study:   50 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Intervention Group:

Inclusion Criteria:

  • Age: ≥ 50 (men) or ≥ 55 (women)
  • Low-density lipoprotein cholesterol (LDL-C) ≥ 70 mg/dL

  • Stable coronary artery disease (without plan to undergo revascularization before randomization) defined as one or more of the following:

    1. Abnormal nuclear perfusion imaging

      1. At least moderate ischemia involving >10% of the LV myocardium or
      2. Global coronary flow reserve (CFR) <1.8 or
      3. Stress myocardial blood flow (MBF) <1.8

    2. Abnormal coronary angiography (invasive coronary angiography or coronary computed tomography)

      1. ≥ 50% stenosis in ≥ 2 coronary vessels or
      2. Diffuse atherosclerosis in a 3-vessel distribution

    3. Elevated coronary calcium score

      1. CAC >100 + >1 ASCVD risk factor
      2. CAC >300
  • If the patient is on a statin they must be on a stable dose for at least 3 months prior to enrollment.

Exclusion Criteria:

  • History of myocardial infarction or stroke
  • CABG < 3 months prior to screening
  • Homozygous familial hypercholesterolemia
  • History of cardiac transplantation
  • LV ejection fraction < 40% or New York Heart Failure Association (NYHA) class III-IV for angina and/or dyspnea.
  • History of infiltrative or hypertrophic cardiomyopathy
  • Severe valvular disease
  • Uncontrolled or recurrent ventricular tachycardia
  • Fasting triglycerides > 500 mg/dL
  • GFR ˂ 30 mL/min/1.73 m²
  • Current use of a PCSK-9 inhibitor
  • Currently pregnant or breastfeeding
  • Contraindication to receive vasodilator agent
  • Latex allergy

Parallel Control Group:

Patients will be invited to participate in the parallel control group if they meet study criteria, but 1) have a latex allergy and cannot use the Evolocumab autoinjector 2) LDL-C is just below the enrollment criteria (LDL 60-69), or 3) meet study criteria but prefer to not take an injectable medication at this time.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05152888


Contacts
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Contact: Marcelo Di Carli, MD 617-732-6290 mdicarli@bwh.harvard.edu
Contact: Leanne Barrett Goldstein 617-732-4719 lbarrett11@bwh.harvard.edu

Locations
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United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Marcelo Di Carli, MD    617-732-6291    mdicarli@bwh.harvard.edu   
Contact: Leanne Barrett Goldstein    617-732-4719    lbarrett11@bwh.harvard.edu   
Sponsors and Collaborators
Brigham and Women's Hospital
Investigators
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Principal Investigator: Marcelo Di Carli, MD Brigham and Women's Hospital
More Information
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Responsible Party: Marcelo F. Di Carli, MD, FACC, Chief, Nuclear Medicine, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT05152888    
Other Study ID Numbers: 2021P003360
First Posted: December 10, 2021    Key Record Dates
Last Update Posted: June 22, 2023
Last Verified: June 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Coronary Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Evolocumab
PCSK9 Inhibitors
Anticholesteremic Agents
 Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Lipid Regulating Agents