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

Atherosclerosis Clinical Trial

— NEWTON-CABG  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03900026
• Other study ID #: NEWTON CABG (Cardiolink-007)
• Status: Recruiting
• Phase: Phase 4
• Start date: May 30, 2019
• Est. completion date: December 1, 2023

Study information

• Verified date: July 2020
• Source: St. Michael's Hospital, Toronto
• Contact: Danusha Nandamalavan
• Phone: 416-864-6060
• Email: NandamalavaD[@]smh.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 766
• Est. completion date: December 1, 2023
• Est. primary completion date: December 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atherosclerosis
• Coronary Artery Bypass Graft Surgery
• Vein Occlusion

Intervention

Drug:
• 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

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

Locations

Country	Name	City	State
Canada	Foothills Medical Centre	Calgary
Canada	University of Alberta	Edmonton	Alberta
Canada	Hamilton Health Sciences	Hamilton	Ontario
Canada	Kingston Health Sciences Centre	Kingston	Ontario
Canada	Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval	Québec	Quebec
Canada	St. Michael's Hospital	Toronto	Ontario
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Maine Medical Center	Portland	Maine

Sponsors (2)

Lead Sponsor	Collaborator
St. Michael's Hospital, Toronto	Applied Health Research Centre

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Composite rate of fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, cardiovascular death, coronary heart disease death, repeat coronary revascularization	composite rate of occurrence of the above mentioned clinical outcomes at 24 months post CABG.	24 months post CABG
Other	Rate of fatal and non-fatal myocardial infarction.	Rate of occurrence of the above mentioned clinical outcome at 24 months post CABG.	24 months post CABG
Other	Rate of fatal and non-fatal stroke.	Rate of occurrence of the above mentioned clinical outcome at 24 months post CABG.	24 months post CABG
Other	Rate of cardiovascular death.	Rate of occurrence of the above mentioned clinical outcome at 24 months post CABG.	24 months post CABG
Other	Rate of coronary heart disease death.	Rate of occurrence of the above mentioned clinical outcome at 24 months post CABG.	24 months post CABG
Other	Rate of repeat coronary revascularization.	Rate of occurrence of the above mentioned clinical outcome at 24 months post CABG.	24 months post CABG
Other	Rate of all-cause mortality.	Proportion of patients who have died at 24 months post CABG.	24 months post CABG
Other	Rate of total vein graft patency at 24 months.	Rate of total vein graft patency defined as 1-VGDR at 24 months post CABG.	24 months post CABG
Other	Percentage of patients free of vein graft disease at 24 months.	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
Other	Vein graft plaque volume.	Volume of vein graft plaque at 24 months post CABG.	24 months post CABG
Primary	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	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.	24 months post CABG
Secondary	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.	24 months post CABG