Effect of Evolocumab on Saphenous Vein Graft Patency Following Coronary Artery Bypass Surgery (NEWTON-CABG)

July 9, 2020 updated by: Unity Health Toronto

A Randomized Trial of Evolocumab on Saphenous Vein Graft Patency Following Coronary Artery Bypass Surgery (NEWTON-CABG)

The purpose of this study is to determine if evolocumab added to regular statin therapy improves vein graft patency after coronary artery bypass graft (CABG) surgery.

Study Overview

Detailed Description

Coronary artery bypass graft (CABG) surgery is a procedure in which an artery or vein from the body is grafted to a critically narrowed coronary artery to restore flow of oxygenated blood to the heart. Statins are frequently prescribed after CABG surgery in order to lower LDL cholesterol levels and reduce the chances of coronary artery obstruction recurring. Despite this preventive measure, new vein grafts do end up becoming blocked in a significant proportion of patients. Evolocumab (Repatha®) is a recently approved medication that has been shown to effectively lower LDL cholesterol levels in the blood.

NEWTON-CABG is an investigator-initiated multicenter, double-blind, randomized, placebo-controlled, parallel group study of evolocumab [140mg administered subcutaneously (SC) every two weeks (Q2W)] added to statin therapy for 24 months postoperatively in a broad population of patients undergoing CABG surgery. Eligible subjects will be randomized to receive evolocumab or placebo within 21 days of index CABG. Prior to randomization, post-operative patients will be on moderate or high intensity statin therapy (atorvastatin 40-80mg, rosuvastatin 20-40mg or simvastatin 40mg daily unless another statin/dose or non-statin alternative is clinically justified). A CTAngiogram will be conducted at 24 months following CABG. Routine study visits will be done 3, 6, 12, 18 and 24 months post-surgery.

This study is supported by Amgen Inc.

Study Type

Interventional

Enrollment (Anticipated)

766

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Alberta
      • Edmonton, Alberta, Canada, T6G 2R8
        • Recruiting
        • University of Alberta
        • Contact:
        • Principal Investigator:
          • Andrew Shaw
    • Ontario
      • Hamilton, Ontario, Canada
        • Recruiting
        • Hamilton Health Sciences
        • Contact:
        • Principal Investigator:
          • Richard Whitlock
      • Kingston, Ontario, Canada, K7L 2V7
      • Toronto, Ontario, Canada, M5B 1W8
    • Quebec
      • Québec, Quebec, Canada
        • Recruiting
        • Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval
        • Contact:
        • Principal Investigator:
          • Francois Dagenais
    • Connecticut
      • New Haven, Connecticut, United States, 06511
        • Recruiting
        • Yale University School of Medicine
        • Contact:
        • Principal Investigator:
          • Umer Darr
    • Florida
      • Jacksonville, Florida, United States, 32216
        • Recruiting
        • Jacksonville Center for Clinical Research
        • Contact:
        • Principal Investigator:
          • Michael Koren
    • Maine
      • Portland, Maine, United States, 04102
        • Recruiting
        • Maine Medical Center
        • Contact:
        • Contact:
          • Phone Number: 207-662-1489

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria - To be considered eligible for participation in this study, a participant must satisfy each of the following criteria:

  1. Age ≥ 18 years
  2. Scheduled to undergo coronary artery bypass graft (CABG) surgery (with or without cardiopulmonary bypass (CPB); with or without single valve repair/replacement)
  3. CABG procedure included/planned to include at least two saphenous vein grafts
  4. CABG procedure occurred within the past 21 days, or is planned within the next 60 days
  5. On a moderate to high intensity statin therapy (defined as atorvastatin 40-80mg daily, rosuvastatin 20-40mg or simvastatin 40mg daily) unless a lower dose, or another statin or non-statin therapy is clinically justified

Exclusion Criteria - A participant will be ineligible for participation in this study if he or she satisfies any one or more of the following criteria:

  1. Patients in whom additional lowering of LDL-C with evolocumab is deemed to be clinically inappropriate
  2. Allergy to contrast dye
  3. Known severe hepatic impairment (Childs-Pugh, Class C).
  4. Known renal disease with estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2
  5. Recipient of any major organ transplant (eg, lung, liver, heart, bone marrow)
  6. Use of cholesterylester transfer protein (CETP) inhibition treatment within 12 months prior to randomization.
  7. Current, prior within past year, or known planned use of PCSK9 inhibition treatment
  8. Severe cardiovascular or concomitant non-cardiovascular disease that is expected to reduce life expectancy to less than 2 years
  9. Major active infection, or major hematologic, renal, respiratory, metabolic, gastrointestinal or endocrine dysfunction
  10. Women who are pregnant or breastfeeding
  11. Women of child bearing potential who are unwilling to use proper family planning or birth control methods to avoid pregnancy. Women are considered post-menopausal and not of childbearing potential after 12 months of natural (spontaneous) amenorrhea or have had a surgical procedure such as hysterectomy which makes pregnancy impossible.
  12. Known intolerance or allergy to evolocumab or other PCSK9 inhibitors.
  13. Currently taking simvastatin >40mg/day, niacin or bile acid sequestrants
  14. Known latex allergy
  15. Inability to comply with protocol-required study visits or procedures, including administration of study drug
  16. Known history of cancer within the past 5 years (except for carcinoma in-situ of the cervix, stage 1 prostate cancer or adequately treated non-melanoma carcinomas of the skin)
  17. Participation in another investigational device or drug study which is likely to affect the primary outcome, within 30 days of planned initiation of study drug
  18. NYHA class IV
  19. Pacemaker or other implantable device implanted within 30 days prior to screening

Additional postoperative exclusion criteria:

  1. Received only <2 vein grafts
  2. Major peri-operative complications following CABG surgery (e.g. stroke, MI, renal failure requiring dialysis, or postoperative ICU stay > 5 days) prior to randomization

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo Treatment
Participants will receive subcutaneous injections of the placebo Q2W (every 2 weeks)
Placebo cartridges will contain vehicle only; placebo will be administered via subcutaneous injection.
Other Names:
  • Control
Experimental: Evolocumab Treatment
Participants will receive subcutaneous injections of 140mg of evolocumab Q2W (every two weeks)
REPATHA (evolocumab) is a human immunoglobulin G2 (IgG2) monoclonal antibody that has high affinity binding to Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9); it will be administered via subcutaneous injection
Other Names:
  • Repatha®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Saphenous vein graft disease rate (VGDR)
Time Frame: 24 months post CABG
Saphenous vein graft disease rate (VGDR) is defined as the proportion of vein grafts with significant stenosis or total occlusion (≥50%) on 64-slice (or greater) cardiac CT angiography (CTA) or clinically indicated coronary angiography.
24 months post CABG

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The proportion of patients with at least 1 vein graft totally (100%) occluded.
Time Frame: 24 months post CABG
Proportion of patients who have at least 1 totally (100%) occluded vein graft at 24 months post CABG.
24 months post CABG
The percentage of vein grafts which are totally (100%) occluded grafts.
Time Frame: 24 months post CABG
Percentage of vein grafts that are totally (100%) occluded at 24 months post CABG.
24 months post CABG

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite rate of fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, cardiovascular death, coronary heart disease death, repeat coronary revascularization
Time Frame: 24 months post CABG
composite rate of occurrence of the above mentioned clinical outcomes at 24 months post CABG.
24 months post CABG
Rate of fatal and non-fatal myocardial infarction.
Time Frame: 24 months post CABG
Rate of occurrence of the above mentioned clinical outcome at 24 months post CABG.
24 months post CABG
Rate of fatal and non-fatal stroke.
Time Frame: 24 months post CABG
Rate of occurrence of the above mentioned clinical outcome at 24 months post CABG.
24 months post CABG
Rate of cardiovascular death.
Time Frame: 24 months post CABG
Rate of occurrence of the above mentioned clinical outcome at 24 months post CABG.
24 months post CABG
Rate of coronary heart disease death.
Time Frame: 24 months post CABG
Rate of occurrence of the above mentioned clinical outcome at 24 months post CABG.
24 months post CABG
Rate of repeat coronary revascularization.
Time Frame: 24 months post CABG
Rate of occurrence of the above mentioned clinical outcome at 24 months post CABG.
24 months post CABG
Rate of all-cause mortality.
Time Frame: 24 months post CABG
Proportion of patients who have died at 24 months post CABG.
24 months post CABG
Rate of total vein graft patency at 24 months.
Time Frame: 24 months post CABG
Rate of total vein graft patency defined as 1-VGDR at 24 months post CABG.
24 months post CABG
Percentage of patients free of vein graft disease at 24 months.
Time Frame: 24 months post CABG
Percentage of patients who are free of vein graft disease at 24 months defined as having no vein grafts with ≥ 50% stenosis.
24 months post CABG
Vein graft plaque volume.
Time Frame: 24 months post CABG
Volume of vein graft plaque at 24 months post CABG.
24 months post CABG

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Subodh Verma, MD, Unity Health Toronto
  • Principal Investigator: David Mazer, MD, Unity Health Toronto
  • Study Chair: Lawrence Leiter, MD, Unity Health Toronto

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 30, 2019

Primary Completion (Anticipated)

December 1, 2023

Study Completion (Anticipated)

December 1, 2023

Study Registration Dates

First Submitted

March 28, 2019

First Submitted That Met QC Criteria

April 1, 2019

First Posted (Actual)

April 2, 2019

Study Record Updates

Last Update Posted (Actual)

July 13, 2020

Last Update Submitted That Met QC Criteria

July 9, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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.

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