E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patency of graft after coronary bypass graft surgery in patients with hyprelipidaemia |
|
E.1.1.1 | Medical condition in easily understood language |
Patency of graft after coronary bypass graft surgery in patients with hyprelipidaemia |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011079 |
E.1.2 | Term | Coronary artery disease NOS |
E.1.2 | System Organ Class | 100000004849 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Given that graft failure is associated with increased morbidity and mortality, and that lipid lowering interventions may reduce vein graft occlusion, the objectives of this study are to determine if intensive LDL-cholesterol lowering with evolocumab will result in improved vein graft patency compared to placebo following CABG surgery. |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 40-80 mg daily, rosuvastatin 20-40 mg, or simvastatin 40 mg daily) unless a lower dose, or another statin or non-statin therapy is clinically justified
|
|
E.4 | Principal 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 >40 mg/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
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the saphenous vein graft disease rate (VGDR) 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.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• The proportion of patients with at least 1 vein graft totally (100%) occluded at 24 months • The percentage of vein grafts which are totally occluded (100%) grafts at 24 months
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Last subject's last visit (LSLV) |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |