Statin Recapture Therapy Before Coronary Artery Bypass Grafting

Phase 4

Completed

• Conditions: Coronary Artery Disease
• Interventions: Drug: Statin Recapture Therapy; Drug: Placebo

• Registration Number: NCT01715714
• Lead Sponsor: University of Cologne

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.

Study Timeline

• Study First Submitted: 2012-10-18
• Study First Submitted QC: 2012-10-26
• Study First Posted: 2012-10-29
• Study Start: 2012-11-07
• Primary Completion: 2019-04-24
• Study Completion: 2020-09-27
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-21
• Last Update Posted: 2022-07-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2630

Inclusion Criteria

1. Patients on chronic statin treatment (>30 days) scheduled for isolated CABG, including on- or off-pump or repeat (redo's) revascularisation procedures
2. Stable or unstable angina, including non ST-segment-elevation acute coronary syndrome (NSTE-ACS)
3. Age ≥ 18 years
4. Written informed consent

Exclusion Criteria

1. Any concomitant cardiovascular procedure to CABG (i.e. valve, aortic or carotid surgery)
2. Acute ST-segment-elevation myocardial infarction (STEMI)
3. NSTE-ACS with cardiogenic shock warranting emergent salvage surgery within 12 hrs from hospital admission
4. History of atrial fibrillation or muscle disease (myopathy)
5. Current renal (creatinine>2x upper limit of normal (ULN), dialysis, kidney transplant) or hepatic dysfunction (AST/ALT>2x ULN, liver transplant or neoplasm)
6. Inability of oral drug intake

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Statin Recapture Therapy	Statin Recapture Therapy	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)
Placebo	Placebo	Placebo given orally 12 hrs and 2 hrs before CABG

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (10)

University of Muenster; 🇩🇪 Muenster, NRW, Germany

University of Aachen; 🇩🇪 Aachen, NRW, Germany

University of Bonn; 🇩🇪 Bonn, NRW, Germany

Heart Center Bad Neustadt; 🇩🇪 Bad Neustadt An Der Saale, Bayern, Germany

Helios Heart Center Wuppertal; 🇩🇪 Wuppertal, NRW, Germany

Heart Center Bad Oeynhausen; 🇩🇪 Bad Oeynhausen, NRW, Germany

University of Bochum; 🇩🇪 Bochum, NRW, Germany

University of Essen; 🇩🇪 Essen, NRW, Germany

Heart Center Freiburg-Bad Krozingen; 🇩🇪 Freiburg, Baden-Württemberg, Germany

University of Cologne; 🇩🇪 Cologne, NRW, Germany