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

NCT ID: NCT03900026

Last Updated: 2025-08-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 782 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-30
• Study Completion Date: 2025-01-30

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.

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.

Conditions

Coronary Artery Bypass Graft Surgery; Atherosclerosis; Vein Occlusion

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo Treatment

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

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

Evolocumab Treatment

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

Group Type: EXPERIMENTAL

Evolocumab

Intervention Type: 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

Interventions

Evolocumab

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

Intervention Type: DRUG

Placebo

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

Intervention Type: OTHER

Other Intervention Names

Repatha®; Control

Eligibility Criteria

Inclusion 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

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Applied Health Research Centre

OTHER

Sponsor Role: collaborator

Unity Health Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Mazer, MD

Role: PRINCIPAL_INVESTIGATOR

Unity Health Toronto

Subodh Verma, MD

Role: PRINCIPAL_INVESTIGATOR

Unity Health Toronto

Lawrence Leiter, MD

Role: STUDY_CHAIR

Unity Health Toronto

Locations

San Francisco VA Medical Center

San Francisco, California, United States

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States

Maine Medical Center

Portland, Maine, United States

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, United States

University Hospital Cleveland Medical Center

Cleveland, Ohio, United States

Royal Adelaide Hospital

Adelaide, , Australia

Flinders Medical Centre

Bedford Park, , Australia

Monash University

Melbourne, , Australia

Fiona Stanley Hospital

Murdoch, , Australia

University of Alberta

Edmonton, Alberta, Canada

New Brunswick Heart Centre

Saint John's, New Brunswick, Canada

Hamilton Health Sciences

Hamilton, Ontario, Canada

Kingston Health Sciences Centre

Kingston, Ontario, Canada

One Heart Care

Mississauga, Ontario, Canada

North York Diagnostic and Cardiology Centre

North York, Ontario, Canada

Sunnybrook Health Sciences Center

North York, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

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

Québec, Quebec, Canada

Foothills Medical Centre

Calgary, , Canada

Medical Centre Hungarian Defence Forces

Budapest, , Hungary

Semmelweis University Heart and Vascular Centre

Budapest, , Hungary

Zala Megyei Szent Rafael Korhaz

Zalaegerszeg, , Hungary

Countries

United States; Australia; Canada; Hungary

References

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.

Reference Type: DERIVED

PMID: 40907505 (View on PubMed)

Other Identifiers

NEWTON CABG (CardioLink-5)

Identifier Type: -

Identifier Source: org_study_id