Statin Recapture Therapy Before Coronary Artery Bypass Grafting (StaRT-CABG)

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Statin Recapture Therapy; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 2630
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Baden-Württemberg
    • Freiburg, Baden-Württemberg, Germany, 79106
      • Heart Center Freiburg-Bad Krozingen
  • Bayern
    • Bad Neustadt An Der Saale, Bayern, Germany, 97616
      • Heart Center Bad Neustadt
  • NRW
    • Aachen, NRW, Germany, 52074
      • University of Aachen
    • Bad Oeynhausen, NRW, Germany, 32545
      • Heart Center Bad Oeynhausen
    • Bochum, NRW, Germany
      • University of Bochum
    • Bonn, NRW, Germany, 53127
      • University of Bonn
    • Cologne, NRW, Germany, 50924
      • University of Cologne
    • Essen, NRW, Germany, 45122
      • University of Essen
    • Muenster, NRW, Germany, 48149
      • University of Muenster
    • Wuppertal, NRW, Germany, 42117
      • Helios Heart Center Wuppertal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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)	Drug: Statin Recapture Therapy; Given 12h and 2h before CABG; Other Names: Simvastatin 80 mg; Atorvastatin 80 mg; Pravastatin 40 mg; Fluvastatin 80 mg
Placebo Comparator: Placebo; Placebo given orally 12 hrs and 2 hrs before CABG	Drug: Placebo; Given 12h and 2h before CABG.

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)

Collaborators and Investigators

• Sponsor: University of Cologne
• Collaborators: German Federal Ministry of Education and Research
• Investigators: Principal Investigator: Oliver J Liakopoulos, MD, PhD, University of Cologne

Publications and helpful links

General Publications

• Liakopoulos OJ, Kuhn EW, Hellmich M, Kuhr K, Krause P, Reuter H, Thurat M, Choi YH, Wahlers T; StaRT-CABG Investigators. Statin Recapture Therapy before Coronary Artery Bypass Grafting Trial: Rationale and study design of a multicenter, randomized, double-blinded controlled clinical trial. Am Heart J. 2015 Jul;170(1):46-54, 54.e1-2. doi: 10.1016/j.ahj.2015.04.015. Epub 2015 Apr 17.

Helpful Links

• StaRT CABG Homepage

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2012
• Primary Completion (Actual): April 24, 2019
• Study Completion (Actual): September 27, 2020

Study Registration Dates

• First Submitted: October 18, 2012
• First Submitted That Met QC Criteria: October 26, 2012
• First Posted (Estimate): October 29, 2012

Study Record Updates

• Last Update Posted (Actual): July 22, 2022
• Last Update Submitted That Met QC Criteria: July 21, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Coronary Artery Disease; Cardiac Surgery; Statins; Coronary Artery Bypass Grafting
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Pravastatin; Simvastatin
• Other Study ID Numbers: Uni-Koeln-1341; 2011-001795-19 (EudraCT Number); DRKS00000753 (Registry Identifier: German Clinical Trials Register (DRKS))