Statin Therapy In Cardiac Surgery

NCT01573143 | Completed Phase 4 DMC

• 1 other identifier: 2.0 /06.09.11
• Study Type: interventional
• Target: 1,922
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of STICS trial (Statin Therapy In Cardiac Surgery) is to test whether perioperative treatment with Rosuvastatin 20 mg once daily prevents post-operative atrial fibrillation and reduces perioperative irreversible myocardial damage in patients undergoing elective cardiac surgery.

Conditions

Atrial Fibrillation; Myocardium; Injury

Keywords

Surgical Procedures, Cardiac; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin; Post operative atrial fibrillation

Outcome Measures

Primary Outcomes (2)

• Post operative atrial fibrillation detected on continuous ECG monitoring.

  Monitoring will commence soon after surgery and will be continued until the end of post operative day 5

• Myocardial injury assessed by Troponin release

  Serial blood samples for Troponin assay will be collected at 6, 24, 48 and 120 hours after surgery

Secondary Outcomes (3)

• Hospital and intensive care unit stay

  Participants will be followed for the duration of the post operative period up to the day of initial discharge from the hospital, an expected average of 7 days.

• Major in-hospital cardiac and/or cerebrovascular events (such as death, stroke, myocardial infarction,heart failure) and acute kidney injury

  Participants will be followed for the duration of the post operative period up to the day of initial discharge from the hospital, an expected average of 7 days.

• Cardiac tissue and plasma/ urine biomarkers

  Post operative period including day 5

Study Arms (2)

Sugar pill

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Rosuvastatin

EXPERIMENTAL

Rosuvastatin (20 mg od)

Drug: Rosuvastatin

Interventions

Rosuvastatin DRUG

Rosuvastatin (20 mg od) started not earlier than 8 days before surgery and continued until the 5th post-operative day included;

Also known as: Crestor

Rosuvastatin

Placebo DRUG

Placebo started not earlier than 8 days before surgery and continued until the 5th post-operative day included.

Sugar pill

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients awaiting elective cardiac surgery who are willing and able to give informed consent for participation in the study and who are in sinus rhythm and not taking any antiarrhythmic medication, other than beta-adrenergic blocking agents, at the time of surgery.

You may not qualify if:

• History of obstructive hepato-biliary disease or other serious hepatic disease
• Untreated hypothyroidism
• Creatinine \> 200 umol/L
• Personal and family history of hereditary muscle disorders
• Known intolerance to statins or history of muscle toxicity with fibrates or statins.
• On-going use of fibrates, niacin or of agents that are strong inhibitors of cytochrome P-450 or the P-glycoprotein within a month preceding randomization (cyclosporine, oral azole antifungals,macrolide antibiotics, protease inhibitors, nefazodone, amiodarone or ≥ 1L/day of grapefruit juice)
• Significant mitral valve disease (moderate or severe mitral regurgitation-eg. \> grade II and/or mitral stenosis \& mitral annular calcification).
• Patients treated with any anti-arrhythmic agent (other than beta-adrenergic receptor blockers).

Sponsors & Collaborators

• University of Oxford: lead
• Chinese Academy of Medical Sciences, Fuwai Hospital: collaborator
• Chinese Academy of Medical Sciences: collaborator
• Peking Union Medical College: collaborator

Study Sites (1)

Fuwai Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100037, China

Location

Related Publications (12)

• Laufs U, Kilter H, Konkol C, Wassmann S, Bohm M, Nickenig G. Impact of HMG CoA reductase inhibition on small GTPases in the heart. Cardiovasc Res. 2002 Mar;53(4):911-20. doi: 10.1016/s0008-6363(01)00540-5.

  PMID: 11922901 BACKGROUND

• Maack C, Kartes T, Kilter H, Schafers HJ, Nickenig G, Bohm M, Laufs U. Oxygen free radical release in human failing myocardium is associated with increased activity of rac1-GTPase and represents a target for statin treatment. Circulation. 2003 Sep 30;108(13):1567-74. doi: 10.1161/01.CIR.0000091084.46500.BB. Epub 2003 Sep 8.

  PMID: 12963641 BACKGROUND

• Kim YM, Guzik TJ, Zhang YH, Zhang MH, Kattach H, Ratnatunga C, Pillai R, Channon KM, Casadei B. A myocardial Nox2 containing NAD(P)H oxidase contributes to oxidative stress in human atrial fibrillation. Circ Res. 2005 Sep 30;97(7):629-36. doi: 10.1161/01.RES.0000183735.09871.61. Epub 2005 Aug 25.

  PMID: 16123335 BACKGROUND

• Kim YM, Kattach H, Ratnatunga C, Pillai R, Channon KM, Casadei B. Association of atrial nicotinamide adenine dinucleotide phosphate oxidase activity with the development of atrial fibrillation after cardiac surgery. J Am Coll Cardiol. 2008 Jan 1;51(1):68-74. doi: 10.1016/j.jacc.2007.07.085.

  PMID: 18174039 BACKGROUND

• European Heart Rhythm Association; European Association for Cardio-Thoracic Surgery; Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, Van Gelder IC, Al-Attar N, Hindricks G, Prendergast B, Heidbuchel H, Alfieri O, Angelini A, Atar D, Colonna P, De Caterina R, De Sutter J, Goette A, Gorenek B, Heldal M, Hohloser SH, Kolh P, Le Heuzey JY, Ponikowski P, Rutten FH. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010 Oct;31(19):2369-429. doi: 10.1093/eurheartj/ehq278. Epub 2010 Aug 29. No abstract available.

  PMID: 20802247 BACKGROUND

• Chen WT, Krishnan GM, Sood N, Kluger J, Coleman CI. Effect of statins on atrial fibrillation after cardiac surgery: a duration- and dose-response meta-analysis. J Thorac Cardiovasc Surg. 2010 Aug;140(2):364-72. doi: 10.1016/j.jtcvs.2010.02.042. Epub 2010 Apr 9.

  PMID: 20381820 BACKGROUND

• Reilly SN, Jayaram R, Nahar K, Antoniades C, Verheule S, Channon KM, Alp NJ, Schotten U, Casadei B. Atrial sources of reactive oxygen species vary with the duration and substrate of atrial fibrillation: implications for the antiarrhythmic effect of statins. Circulation. 2011 Sep 6;124(10):1107-17. doi: 10.1161/CIRCULATIONAHA.111.029223. Epub 2011 Aug 15.

  PMID: 21844076 BACKGROUND

• Antoniades C, Bakogiannis C, Leeson P, Guzik TJ, Zhang MH, Tousoulis D, Antonopoulos AS, Demosthenous M, Marinou K, Hale A, Paschalis A, Psarros C, Triantafyllou C, Bendall J, Casadei B, Stefanadis C, Channon KM. Rapid, direct effects of statin treatment on arterial redox state and nitric oxide bioavailability in human atherosclerosis via tetrahydrobiopterin-mediated endothelial nitric oxide synthase coupling. Circulation. 2011 Jul 19;124(3):335-45. doi: 10.1161/CIRCULATIONAHA.110.985150. Epub 2011 Jul 5.

  PMID: 21730307 BACKGROUND

• Antoniades C, Demosthenous M, Reilly S, Margaritis M, Zhang MH, Antonopoulos A, Marinou K, Nahar K, Jayaram R, Tousoulis D, Bakogiannis C, Sayeed R, Triantafyllou C, Koumallos N, Psarros C, Miliou A, Stefanadis C, Channon KM, Casadei B. Myocardial redox state predicts in-hospital clinical outcome after cardiac surgery effects of short-term pre-operative statin treatment. J Am Coll Cardiol. 2012 Jan 3;59(1):60-70. doi: 10.1016/j.jacc.2011.08.062.

  PMID: 22192670 BACKGROUND

• Zeng Z, Li F, Gai S, Chen R, Wang P, Wang J, Yang Y, Chen J, Zhang X, Wang X, Han Y, Lei C, Li X, Liu H, Zheng Z. The effect of clonal hematopoiesis on long-term outcomes in patients undergoing coronary artery bypass grafting. BMC Med. 2025 May 30;23(1):322. doi: 10.1186/s12916-025-04140-9.

  PMID: 40442635 DERIVED

• Liu H, Xu Z, Sun C, Chen Q, Bao N, Chen W, Zhou Z, Wang X, Zheng Z. Perioperative urinary thromboxane metabolites and outcome of coronary artery bypass grafting: a nested case-control study. BMJ Open. 2018 Aug 30;8(8):e021219. doi: 10.1136/bmjopen-2017-021219.

  PMID: 30166295 DERIVED

• Zheng Z, Jayaram R, Jiang L, Emberson J, Zhao Y, Li Q, Du J, Guarguagli S, Hill M, Chen Z, Collins R, Casadei B. Perioperative Rosuvastatin in Cardiac Surgery. N Engl J Med. 2016 May 5;374(18):1744-53. doi: 10.1056/NEJMoa1507750.

  PMID: 27144849 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation; Wounds and Injuries

Interventions

Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Rory Collins, FRCP. FMed Sci

  Clinical Trial Service Unit (CTSU), University of Oxford

  STUDY CHAIR

• Shenshou Hu, MD.PhD

  Chinese Academy of Medical Sciences, Fuwai Hospital

  STUDY CHAIR

• Barbara Casadei, MD.DPhil.FRCP

  Department of Cardiovascular Medicine, John Radcliffe Hospital, University of Oxford

  PRINCIPAL INVESTIGATOR

• Zheng Zhe, MD.PhD

  Chinese Academy of Medical Sciences, Fuwai Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2012
• First Posted: April 6, 2012
• Study Start: September 1, 2011
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: September 17, 2014

Record last verified: 2014-09

Locations

CN (1)