Effect of Evolocumab on Saphenous Vein Graft Patency Following Coronary Artery Bypass Surgery (NEWTON-CABG)
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|ClinicalTrials.gov Identifier: NCT03900026|
Recruitment Status : Recruiting
First Posted : April 2, 2019
Last Update Posted : July 13, 2020
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|Condition or disease||Intervention/treatment||Phase|
|Coronary Artery Bypass Graft Surgery Atherosclerosis Vein Occlusion||Drug: Evolocumab Other: Placebo||Phase 4|
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 (Clinical Trial)|
|Estimated Enrollment :||766 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Multicenter, double-blind, randomized, placebo-controlled, parallel group study of evolocumab.|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Randomized Trial of Evolocumab on Saphenous Vein Graft Patency Following Coronary Artery Bypass Surgery (NEWTON-CABG)|
|Actual Study Start Date :||May 30, 2019|
|Estimated Primary Completion Date :||December 1, 2023|
|Estimated Study Completion Date :||December 1, 2023|
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 Name: 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 Name: Repatha®
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Rate of cardiovascular death. [ Time Frame: 24 months post CABG ]Rate of occurrence of the above mentioned clinical outcome at 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.
- 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.
- Rate of all-cause mortality. [ Time Frame: 24 months post CABG ]Proportion of patients who have died at 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.
- 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.
- Vein graft plaque volume. [ Time Frame: 24 months post CABG ]Volume of vein graft plaque at 24 months post CABG.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
Inclusion Criteria - To be considered eligible for participation in this study, a participant must satisfy each of the following criteria:
- 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
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:
- 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
- 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)
- 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
- NYHA class IV
- Pacemaker or other implantable device implanted within 30 days prior to screening
Additional postoperative exclusion criteria:
- Received only <2 vein grafts
- Major peri-operative complications following CABG surgery (e.g. stroke, MI, renal failure requiring dialysis, or postoperative ICU stay > 5 days) prior to randomization
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03900026
|Contact: Danusha Nandamalavan||416-864-6060 ext 77038||NandamalavaD@smh.ca|
|United States, Connecticut|
|Yale University School of Medicine||Recruiting|
|New Haven, Connecticut, United States, 06511|
|Contact: Kimberly Kunze 203-737-2150 email@example.com|
|Principal Investigator: Umer Darr|
|United States, Florida|
|Jacksonville Center for Clinical Research||Recruiting|
|Jacksonville, Florida, United States, 32216|
|Contact: Heather Burns 904-576-0166 firstname.lastname@example.org|
|Principal Investigator: Michael Koren|
|United States, Maine|
|Maine Medical Center||Recruiting|
|Portland, Maine, United States, 04102|
|Contact: Betsey Gallant WIGHTA@mmc.org|
|Principal Investigator: Robert Kramer|
|University of Alberta||Recruiting|
|Edmonton, Alberta, Canada, T6G 2R8|
|Contact: Maliha Muneer 780-407-8614 email@example.com|
|Principal Investigator: Andrew Shaw|
|Hamilton Health Sciences||Recruiting|
|Hamilton, Ontario, Canada|
|Contact: Courtney Mullen 905.521.2100 ext 44342 Courtney.Mullen@phri.ca|
|Principal Investigator: Richard Whitlock|
|Kingston Health Sciences Centre||Recruiting|
|Kingston, Ontario, Canada, K7L 2V7|
|Contact: Deborah DuMerton 613-549-6666 ext 3224 Deborah.DuMerton@kingstonhsc.ca|
|Principal Investigator: Tarit Saha|
|St. Michael's Hospital||Recruiting|
|Toronto, Ontario, Canada, M5B 1W8|
|Contact: Shira Brodutch 416-864-6060 ext 49419 Shira.Brodutch@unityhealth.to|
|Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval||Recruiting|
|Québec, Quebec, Canada|
|Contact: Hugo Tremblay 418-656-8711 ext 3797 firstname.lastname@example.org|
|Principal Investigator: Francois Dagenais|
|Foothills Medical Centre||Recruiting|
|Contact: Karen Maier Karen.Maier@albertahealthservices.ca|
|Principal Investigator: Alex Gregory|
|Principal Investigator:||David Mazer, MD||Unity Health Toronto|
|Principal Investigator:||Subodh Verma, MD||Unity Health Toronto|
|Study Chair:||Lawrence Leiter, MD||Unity Health Toronto|
|Responsible Party:||Unity Health Toronto|
|Other Study ID Numbers:||
NEWTON CABG (Cardiolink-007)
|First Posted:||April 2, 2019 Key Record Dates|
|Last Update Posted:||July 13, 2020|
|Last Verified:||July 2020|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
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