Statin Recapture Therapy Before Coronary Artery Bypass Grafting

Study Overview
=================
Brief Summary
-----------------
Patients with coronary artery disease requiring coronary artery bypass grafting (CABG) are at risk for postoperative complications after surgery. The StaRT-CABG trial is the first large-scale (2,630 patients) that will investigate whether an additional treatment with statins (lipid-lowering medication) in high doses before CABG surgery can reduce the incidence of major post-surgery complications including death, myocardial infarction and stroke. The StaRT-CABG trial will be recruiting patients from 8 cardiac surgery centres in Germany and is expected to provide relevant clinical data on the efficacy of this novel treatment in order to optimize the care for all patients undergoing CABG.

Detailed Description
-----------------
Patients with coronary artery disease (CAD) requiring coronary artery bypass grafting (CABG) are still at significant risk for postoperative major adverse cardiocerebral events (≈15% MACCE rate), with ≈3% of patients dying within 30 days of surgery. Recent clinical evidence shows that cardioprotection in patients receiving chronic statin treatment can be further improved by a high-dose statin 'recapture' therapy given shortly before an ischemia-reperfusion sequence, resulting in a 61% risk reduction for MACE at 30 days in patients undergoing PCI. Evaluation of this novel approach in the setting of CABG seems particularly promising, as myocardial injury, surgery-related inflammation and pre-existing patients' comorbidities play a pivotal role for poor clinical outcomes after CABG that may be improved by an acute statin recapture therapy. The StaRT-CABG trial is the first large-scale (n=2,630 CABG patients), multicentre (8 cardiac surgery centres), randomised, double-blind and placebo-controlled trial that aims to test whether an acute high-dose statin recapture therapy given shortly before CABG reduces the incidence of MACCE at 30 days after surgery (composite primary outcome: all-cause mortality; non-fatal myocardial infarction and cerebrovascular events). The StaRT-CABG trial is expected to provide highly relevant clinical data on the efficacy of this novel therapeutic approach in order to optimize the care for all CAD patients undergoing CABG with broad clinical implications on current clinical practice and existing guidelines.

Official Title
-----------------
Statin Recapture Therapy Before Coronary Artery Bypass Grafting

Conditions
-----------------
Coronary Artery Disease

Intervention / Treatment
-----------------
* Drug: Statin Recapture Therapy
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients on chronic statin treatment (>30 days) scheduled for isolated CABG, including on- or off-pump or repeat (redo's) revascularisation procedures Stable or unstable angina, including non ST-segment-elevation acute coronary syndrome (NSTE-ACS) Age ≥ 18 years Written informed consent Exclusion Criteria: Any concomitant cardiovascular procedure to CABG (i.e. valve, aortic or carotid surgery) Acute ST-segment-elevation myocardial infarction (STEMI) NSTE-ACS with cardiogenic shock warranting emergent salvage surgery within 12 hrs from hospital admission History of atrial fibrillation or muscle disease (myopathy) Current renal (creatinine>2x upper limit of normal (ULN), dialysis, kidney transplant) or hepatic dysfunction (AST/ALT>2x ULN, liver transplant or neoplasm) Inability of oral drug intake

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Statin Recapture Therapy<br>Oral statin reload of patients at 12 and 2 hours before CABG using the maximal dose of the chronically prescribed statin* on admission. (*simvastatin 80 mg, atorvastatin 80 mg, fluvastatin 80 mg or pravastatin 40 mg) | Drug: Statin Recapture Therapy<br>* Given 12h and 2h before CABG<br>* Other names: Fluvastatin 80 mg;|
| Placebo Comparator: Placebo<br>Placebo given orally 12 hrs and 2 hrs before CABG | Drug: Placebo<br>* Given 12h and 2h before CABG.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major adverse cardiocerebral events (MACCE) within 30 days after CABG. | Composite endpoint consisting of (1) all-cause mortality, (2) non-fatal myocardial infarction (MI) and (3) non-fatal cerebrovascular event (stroke or TIA). | 30 days after Surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major adverse cardiac events | Composite outcome consisting cardiac mortality and non-fatal MI within 30 days after surgery. | 30 days after Surgery | 
| Length of stay | Length of stay on intensive care unit (ICU) and hospital | within the first 15 days after surgery (plus or minus 5 days) | 
| Repeat coronary revascularisation | Repeat coronary revascularisation (PCI or CABG) | 30 days after surgery | 
| Mortality at 12 months | All-cause mortality at 12 months | 12 months after surgery | 
| Wound Infections | Surgical site wound infections. | 30 days after surgery | 
| Atrial fibrillation | New-onset postoperative atrial fibrillation | within the first 15 days after surgery (plus or minus 5 days) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Coronary Artery Disease, Statins, Coronary Artery Bypass Grafting, Cardiac Surgery