Lowering the Risk of Operative Complications Using Atorvastatin Loading Dose

NCT01543555 | Completed Phase 3 DMC

• 1 other identifier: 02/15/2012
• Study Type: interventional
• Target: 648
• Locations: 1 country
• Sites: 1

Brief Summary

Patients submitted to noncardiac surgeries are at increased risk of serious cardiovascular complications. Statins have shown to lower cholesterol levels and reduce cardiovascular events in other scenarios. The objective of this study is to explore the effects of atorvastatin, as compared with placebo, on the 30-day risk of a composite of death, nonfatal Myocardial Injury after Noncardiac Surgery (MINS), or stroke among patients who undergo noncardiac surgery.

Conditions

Myocardial Infarction; Peripheral Vascular Disease; Aortic Aneurism

Keywords

myocardial infarction; statin; perioperative care; peripheral vascular diseases; anesthesiology

Outcome Measures

Primary Outcomes (1)

• Composite outcome

  Composite of all-cause mortality, nonfatal myocardial injury after noncardiac surgery and stroke at 30 days.

  30 days

Secondary Outcomes (9)

• All-cause mortality

  30 days

• Myocardial injury after noncardiac surgery (MINS)

  30 days

• Stroke

  30 days

• Myocardial infarction

  30 days

• Cardiovascular death

  30 days

Study Arms (2)

Atorvastatin active

EXPERIMENTAL

Atorvastatin 80mg anytime within 18 hours before surgery. A postoperative 40mg atorvastatin dose administered at least 12 hours after the 80mg loading dose. Subsequently, 40mg atorvastatin daily for the next seven days.

Drug: Atorvastatin

Placebo

PLACEBO COMPARATOR

Matching placebo 80mg anytime within 18 hours before surgery. A postoperative 40mg placebo dose administered at least 12 hours after the 80mg loading dose. Subsequently, 40mg placebo daily for the next seven days.

Drug: Placebo

Interventions

Atorvastatin DRUG

Atorvastatin 80mg anytime within 18 hours before surgery. A postoperative 40mg atorvastatin dose administered at least 12 hours after the 80mg loading dose. Subsequently, 40mg atorvastatin daily for the next seven days.

Also known as: Liptor (R), Kolevas (R)

Atorvastatin active

Placebo DRUG

Matching placebo 80mg anytime within 18 hours before surgery. A postoperative 40mg matching placebo dose administered at least 12 hours after the 80mg loading dose. Subsequently, 40mg placebo daily for the next seven days.

Also known as: Standard care

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients older than 40 years-old undergoing non-cardiac surgery with an expected hospital stay of at least 24hs and that fulfills any one of the following criteria:
• A) Established vascular disease:
• i) Major vascular surgery ii) All types of surgery in patients with overt atherosclerosis (any significant or symptomatic coronary, cerebral or peripheral artery disease)
• B) Without established vascular disease:
• At least 3 risk factors for cardiovascular complications:
• Major surgery;
• Emergency surgery;
• Previous history of heart failure;
• diabetes;
• Arterial hypertension;
• Smoking habit along the last two years;
• chronic kidney disease (creatinine greater than 2mg/dl);
• Patients older than 70 years.

You may not qualify if:

• Previous intolerance to statins
• Current rhabdomyolysis
• Current use of statins
• Severe Liver Failure (CHILD-PUGH SCORE C)
• Breast-feeding or pregnancy
• Low-risk surgeries

Sponsors & Collaborators

• Hospital do Coracao: lead

Study Sites (1)

Hospital do Coração

São Paulo, São Paulo, 04005-000, Brazil

Location

Related Publications (6)

• POISE Study Group; Devereaux PJ, Yang H, Yusuf S, Guyatt G, Leslie K, Villar JC, Xavier D, Chrolavicius S, Greenspan L, Pogue J, Pais P, Liu L, Xu S, Malaga G, Avezum A, Chan M, Montori VM, Jacka M, Choi P. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet. 2008 May 31;371(9627):1839-47. doi: 10.1016/S0140-6736(08)60601-7. Epub 2008 May 12.

  PMID: 18479744 BACKGROUND

• Kapoor AS, Kanji H, Buckingham J, Devereaux PJ, McAlister FA. Strength of evidence for perioperative use of statins to reduce cardiovascular risk: systematic review of controlled studies. BMJ. 2006 Dec 2;333(7579):1149. doi: 10.1136/bmj.39006.531146.BE. Epub 2006 Nov 6.

  PMID: 17088313 BACKGROUND

• Durazzo AE, Machado FS, Ikeoka DT, De Bernoche C, Monachini MC, Puech-Leao P, Caramelli B. Reduction in cardiovascular events after vascular surgery with atorvastatin: a randomized trial. J Vasc Surg. 2004 May;39(5):967-75; discussion 975-6. doi: 10.1016/j.jvs.2004.01.004.

  PMID: 15111846 BACKGROUND

• Dunkelgrun M, Boersma E, Schouten O, Koopman-van Gemert AW, van Poorten F, Bax JJ, Thomson IR, Poldermans D; Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group. Bisoprolol and fluvastatin for the reduction of perioperative cardiac mortality and myocardial infarction in intermediate-risk patients undergoing noncardiovascular surgery: a randomized controlled trial (DECREASE-IV). Ann Surg. 2009 Jun;249(6):921-6. doi: 10.1097/SLA.0b013e3181a77d00.

  PMID: 19474688 BACKGROUND

• Schouten O, Boersma E, Hoeks SE, Benner R, van Urk H, van Sambeek MR, Verhagen HJ, Khan NA, Dunkelgrun M, Bax JJ, Poldermans D; Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group. Fluvastatin and perioperative events in patients undergoing vascular surgery. N Engl J Med. 2009 Sep 3;361(10):980-9. doi: 10.1056/NEJMoa0808207.

  PMID: 19726772 BACKGROUND

• Patti G, Cannon CP, Murphy SA, Mega S, Pasceri V, Briguori C, Colombo A, Yun KH, Jeong MH, Kim JS, Choi D, Bozbas H, Kinoshita M, Fukuda K, Jia XW, Hara H, Cay S, Di Sciascio G. Clinical benefit of statin pretreatment in patients undergoing percutaneous coronary intervention: a collaborative patient-level meta-analysis of 13 randomized studies. Circulation. 2011 Apr 19;123(15):1622-32. doi: 10.1161/CIRCULATIONAHA.110.002451. Epub 2011 Apr 4.

  PMID: 21464051 BACKGROUND

MeSH Terms

Conditions

Myocardial Infarction; Peripheral Vascular Diseases

Interventions

Atorvastatin; Standard of Care

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Otávio Berwanger, MD, PhD

  Hospital do Coração

  STUDY CHAIR

• Renato D Lopes, MD Phd

  Brazilian Clinical Research Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Institute HCor

Study Record Dates

• First Submitted: February 27, 2012
• First Posted: March 5, 2012
• Study Start: November 1, 2012
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: December 31, 2015

Record last verified: 2015-12

Locations

BR (1)