Atherosclerosis, Coronary Artery Bypass Graft Surgery, Vein Occlusion
Conditions
Keywords
Coronary Artery Bypass Surgery, CABG, Saphenous Vein Graft, Evolocumab, Repatha
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.
Interventions
DRUGEvolocumab
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
OTHERPlacebo
Placebo cartridges will contain vehicle only; placebo will be administered via subcutaneous injection.
Sponsors
Applied Health Research Centre
Unity Health Toronto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Multicenter, double-blind, randomized, placebo-controlled, parallel group study of evolocumab.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Saphenous vein graft disease rate (VGDR) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The proportion of patients with at least 1 vein graft totally (100%) occluded. | 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. | 24 months post CABG | Percentage of vein grafts that are totally (100%) occluded at 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 | 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 a. 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Rate of coronary heart disease death. | 24 months post CABG | Rate of occurrence of the above mentioned clinical outcome at 24 months post CABG. |
| Rate of repeat coronary revascularization. | 24 months post CABG | Rate of occurrence of the above mentioned clinical outcome at 24 months post CABG. |
| Rate of all-cause mortality. | 24 months post CABG | Proportion of patients who have died 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 | 24 months post CABG | composite rate of occurrence of the above mentioned clinical outcomes at 24 months post CABG. |
| Percentage of patients free of vein graft disease at 24 months. | 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. | 24 months post CABG | Volume of vein graft plaque at 24 months post CABG. |
| Rate of total vein graft patency at 24 months. | 24 months post CABG | Rate of total vein graft patency defined as 1-VGDR at 24 months post CABG. |
| Rate of fatal and non-fatal myocardial infarction. | 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. | 24 months post CABG | Rate of occurrence of the above mentioned clinical outcome at 24 months post CABG. |
| Rate of cardiovascular death. | 24 months post CABG | Rate of occurrence of the above mentioned clinical outcome at 24 months post CABG. |
Countries
Australia, Canada, Hungary, United States
Outcome results
None listed