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

NCT03900026 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: NEWTON CABG (CardioLink-5)
• Study Type: interventional
• Target: 782
• Locations: 4 countries
• Sites: 22

Brief 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.

Conditions

Coronary Artery Bypass Graft Surgery; Atherosclerosis; Vein Occlusion

Keywords

Coronary Artery Bypass Surgery; CABG; Saphenous Vein Graft; Evolocumab; Repatha

Outcome Measures

Primary Outcomes (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.

  24 months post CABG

Secondary Outcomes (3)

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

  24 months post CABG

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

  24 months post CABG

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

  24 months post CABG

Other Outcomes (10)

• Composite rate of fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, cardiovascular death, coronary heart disease death, repeat coronary revascularization

  24 months post CABG

• Rate of fatal and non-fatal myocardial infarction.

  24 months post CABG

• Rate of fatal and non-fatal stroke.

  24 months post CABG

Study Arms (2)

Placebo Treatment

PLACEBO COMPARATOR

Participants will receive subcutaneous injections of the placebo Q2W (every 2 weeks)

Other: Placebo

Evolocumab Treatment

EXPERIMENTAL

Participants will receive subcutaneous injections of 140mg of evolocumab Q2W (every two weeks)

Drug: Evolocumab

Interventions

Evolocumab DRUG

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

Also known as: Repatha®

Evolocumab Treatment

Placebo OTHER

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

Also known as: Control

Placebo Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Scheduled to undergo coronary artery bypass graft (CABG) surgery (with or without cardiopulmonary bypass (CPB); with or without single valve repair/replacement)
• CABG procedure included/planned to include at least two saphenous vein grafts
• CABG procedure occurred within the past 21 days, or is planned within the next 60 days
• 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

You may not qualify if:

• Patients in whom additional lowering of LDL-C with evolocumab is deemed to be clinically inappropriate
• Allergy to contrast dye
• Known severe hepatic impairment (Childs-Pugh, Class C).
• Known renal disease with estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73m2
• Recipient of any major organ transplant (eg, lung, liver, heart, bone marrow)
• Use of cholesterylester transfer protein (CETP) inhibition treatment within 12 months prior to randomization.
• Current, prior within past year, or known planned use of PCSK9 inhibition treatment
• Severe cardiovascular or concomitant non-cardiovascular disease that is expected to reduce life expectancy to less than 2 years
• Major active infection, or major hematologic, renal, respiratory, metabolic, gastrointestinal or endocrine dysfunction
• Women who are pregnant or breastfeeding
• 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.
• Known intolerance or allergy to evolocumab or other PCSK9 inhibitors.
• Currently taking simvastatin \>40mg/day, niacin or bile acid sequestrants
• Known latex allergy
• Inability to comply with protocol-required study visits or procedures, including administration of study drug

Sponsors & Collaborators

• Unity Health Toronto: lead
• Applied Health Research Centre: collaborator

Study Sites (22)

San Francisco VA Medical Center

San Francisco, California, 94121, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

Location

Maine Medical Center

Portland, Maine, 04102, United States

Location

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, 55407, United States

Location

University Hospital Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Royal Adelaide Hospital

Adelaide, Australia

Location

Flinders Medical Centre

Bedford Park, Australia

Location

Monash University

Melbourne, Australia

Location

Fiona Stanley Hospital

Murdoch, Australia

Location

University of Alberta

Edmonton, Alberta, T6G 2R8, Canada

Location

New Brunswick Heart Centre

Saint John's, New Brunswick, Canada

Location

Hamilton Health Sciences

Hamilton, Ontario, Canada

Location

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

Location

One Heart Care

Mississauga, Ontario, Canada

Location

North York Diagnostic and Cardiology Centre

North York, Ontario, Canada

Location

Sunnybrook Health Sciences Center

North York, Ontario, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

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

Québec, Quebec, Canada

Location

Foothills Medical Centre

Calgary, Canada

Location

Medical Centre Hungarian Defence Forces

Budapest, Hungary

Location

Semmelweis University Heart and Vascular Centre

Budapest, Hungary

Location

Zala Megyei Szent Rafael Korhaz

Zalaegerszeg, Hungary

Location

Related Publications (1)

• 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.

  PMID: 40907505 DERIVED

MeSH Terms

Conditions

Atherosclerosis

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• David Mazer, MD

  Unity Health Toronto

  PRINCIPAL INVESTIGATOR

• Subodh Verma, MD

  Unity Health Toronto

  PRINCIPAL INVESTIGATOR

• Lawrence Leiter, MD

  Unity Health Toronto

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter, double-blind, randomized, placebo-controlled, parallel group study of evolocumab.

Study Record Dates

• First Submitted: March 28, 2019
• First Posted: April 2, 2019
• Study Start: May 30, 2019
• Primary Completion: January 30, 2025
• Study Completion: January 30, 2025
• Last Updated: August 29, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (10); HU (3); US (5); AU (4)