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Coronary Artery Bypass Graft SurgeryPhase 4NEWTON-CABGNCT03900026

Effect of Evolocumab on Saphenous Vein Graft Patency Following Coronary Artery Bypass Surgery

A Phase 4 study testing Evolocumab in people with Coronary Artery Bypass Graft Surgery and Atherosclerosis, run by Unity Health Toronto at 22 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Evolocumab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
782 participants
Where
22 sitesin 4 countries
Study dates
30 May 2019to 30 Jan 2025
Phase
Phase 4

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

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

Trial locations and contacts

22 sites in 4 countries.

22 sites in 4 countries

Canada10 sites
  • Foothills Medical Centre

    Calgary

  • University of Alberta

    Edmonton, Alberta, T6G 2R8

  • Hamilton Health Sciences

    Hamilton, Ontario

  • Kingston Health Sciences Centre

    Kingston, Ontario, K7L 2V7

  • One Heart Care

    Mississauga, Ontario

  • North York Diagnostic and Cardiology Centre

    North York, Ontario

  • Sunnybrook Health Sciences Center

    North York, Ontario

  • Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval

    Québec, Quebec

  • New Brunswick Heart Centre

    Saint John's, New Brunswick

  • St. Michael's Hospital

    Toronto, Ontario, M5B 1W8

Other trials in Canada

United States5 sites
  • University Hospital Cleveland Medical Center

    Cleveland, Ohio, 44106

  • Jacksonville Center for Clinical Research

    Jacksonville, Florida, 32216

  • Minneapolis Heart Institute Foundation

    Minneapolis, Minnesota, 55407

  • Maine Medical Center

    Portland, Maine, 04102

  • San Francisco VA Medical Center

    San Francisco, California, 94121

Other trials in United States

Australia4 sites
  • Royal Adelaide Hospital

    Adelaide

  • Flinders Medical Centre

    Bedford Park

  • Monash University

    Melbourne

  • Fiona Stanley Hospital

    Murdoch

Other trials in Australia

Hungary3 sites
  • Medical Centre Hungarian Defence Forces

    Budapest

  • Semmelweis University Heart and Vascular Centre

    Budapest

  • Zala Megyei Szent Rafael Korhaz

    Zalaegerszeg

Other trials in Hungary

About this study

Official title: 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.

Read the 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.

Being tested
Evolocumab, Placebo
Keywords
Coronary Artery Bypass Surgery, CABG, Saphenous Vein Graft, Evolocumab, Repatha
Medical subject headings
Atherosclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EvolocumabDrug

    Also called Repatha®

    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

  • PlaceboOther

    Also called Control

    Placebo cartridges will contain vehicle only; placebo will be administered via subcutaneous injection.

Study groups in NCT03900026
Study groupRoleWhat they receive
Placebo TreatmentPlacebo comparatorParticipants will receive subcutaneous injections of the placebo Q2W (every 2 weeks)
Receives: Other: Placebo
Evolocumab TreatmentExperimentalParticipants will receive subcutaneous injections of 140mg of evolocumab Q2W (every two weeks)
Receives: Drug: Evolocumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Saphenous vein graft disease rate (VGDR)

    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.

    Measured: 24 months post CABG

Secondary outcomes (3)
  1. The proportion of patients with at least 1 vein graft totally (100%) occluded.

    Proportion of patients who have at least 1 totally (100%) occluded vein graft at 24 months post CABG.

    Measured: 24 months post CABG

  2. The percentage of vein grafts which are totally (100%) occluded grafts.

    Percentage of vein grafts that are totally (100%) occluded at 24 months post CABG.

    Measured: 24 months post CABG

  3. Hierarchical composite of the following (each assessed by total wins for each treatment group and the win ratio):

    1. time to cardiovascular death from baseline to end of study
    2. time to first myocardial infarction from baseline to end of study
    3. time to first coronary revascularization from baseline to end of study
    4. number of vein grafts with 100% stenosis at end of study
    5. number of vein grafts with 50-99% stenosis at end of study
    6. number of occluded arterial grafts at end of study
    7. total plaque volume at end of study
    8. time to cardiovascular death from baseline to end of study b. time to first myocardial infarction from baseline to end of study c. time to first coronary revascularization from baseline to end of study d. number of vein grafts with 100% stenosis at end of study e. number of vein grafts with 50-99% stenosis at end of study f. number of occluded arterial grafts at end of study g. total plaque volume at end of study

    Measured: 24 months post CABG

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Apr 2019
  2. Study start30 May 2019
  3. Primary completion30 Jan 2025
  4. Study completion30 Jan 2025

Resources

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
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
Multicenter, double-blind, randomized, placebo-controlled, parallel group study of evolocumab.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
782 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03900026
Sponsor's protocol ID
NEWTON CABG (CardioLink-5)
Acronym
NEWTON-CABG
Status last verified
May 2025
First submitted
28 Mar 2019
Last updated
29 Aug 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Verma S, Leiter LA, Teoh H, Mancini GBJ, Quan A, Elituv R, Verma M, Misner E, Szarek M, Thorpe KE, Saha T, Whitlock RP, Yanagawa B, Merkely B, Juni P, Koren MJ, Nicholls SJ, Bhatt DL, Mazer CD. Effect of evolocumab on saphenous vein graft patency after coronary artery bypass surgery (NEWTON-CABG CardioLink-5): an international, randomised, double-blind, placebo-controlled trial. Lancet. 2025 Sep 20;406(10509):1223-1234. doi: 10.1016/S0140-6736(25)01633-2. Epub 2025 Sep 1.

    PubMed 40907505

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