PeriOperative ISchemic Evaluation-3 Trial: A Pilot Study

NCT02546648 | Completed Phase 3

• 1 other identifier: POISE3034
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

A placebo-controlled, factorial trial to assess the impact of rosuvastatin and tranexamic acid (TXA) in patients undergoing noncardiac surgery who are at risk of a perioperative cardiovascular event.

Conditions

Atherosclerotic Disease; Perioperative Bleeding

Outcome Measures

Primary Outcomes (2)

• Postoperative intervention discontinuation

  Interruption of the intervention longer than 24 hours within the first 10 days postoperatively, and longer than 48 hours from postoperative day 10 to 30.

  Postoperative day 1 to 30.

• Change in hemoglobin

  Change in preoperative hemoglobin to the morning hemoglobin recorded on day 1 after surgery.

  Postoperative day 1.

Secondary Outcomes (3)

• All-cause mortality

  Postoperative day 30.

• Non-fatal myocardial infarction

  Postoperative day 30.

• A composite of vascular mortality and non-fatal: myocardial infarction, stroke, cardiac arrest, pulmonary embolus, deep venous thrombosis, life threatening bleeding, major bleeding.

  Postoperative day 30.

Other Outcomes (2)

• Safety Outcomes for Rosuvastatin assessed by Statin induced myopathy

  Postoperative day 30.

• Safety Outcomes for Tranexamic Acid assessed by Seizure, pulmonary emboli, deep venous thrombosis, vascular mortality

  Postoperative day 30.

Study Arms (2)

Tranexamic Acid vs. matching placebo

EXPERIMENTAL

Tranexamic Acid 1g bolus with anesthesia induction followed by 1g bolus at the start of surgical closure.

Drug: Tranexamic Acid; Drug: Tranexamic Acid Placebo

Rosuvastatin vs. matching placebo

EXPERIMENTAL

Rosuvastatin 20 mg orally or matching placebo once per day until 30 days after surgery

Drug: Rosuvastatin or matching placebo

Interventions

Tranexamic Acid DRUG

Also known as: Cyklokapron

Tranexamic Acid vs. matching placebo

Tranexamic Acid Placebo DRUG

Tranexamic Acid vs. matching placebo

Rosuvastatin or matching placebo DRUG

Subjects who are not on a statin will also be randomized to Rosuvastatin or Rosuvastatin placebo. 40mg preoperatively, followed by 20mg postoperatively (4-6 hours after surgical close) and 20mg/day for 30 days postoperatively.

Also known as: Crestor

Rosuvastatin vs. matching placebo

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• undergoing noncardiac surgery
• \>45 years of age
• expected to require at least an overnight hospital admission after surgery; AND
• have a preoperative NT-pro-BNP measurement \>100 ng/mL; OR
• if a preoperative NT-pro-BNP measurement is not available, then the patient must fulfill 1 or more of the following 5 criteria:
• history of coronary artery disease
• history of peripheral vascular disease
• history of stroke
• undergoing major vascular surgery
• have any 3 of the following 9 risk criteria:
• undergoing major surgery
• history of congestive heart failure
• history of a transient ischemic attack
• diabetic and currently taking an oral hypoglycemic agent or insulin
• age \>70 years

You may not qualify if:

• planned use of systemic Tranexamic Acid during surgery
• hypersensitivity or known allergy to TXA
• creatinine clearance \<30 mL/min (MDRD)
• history of seizure disorder
• history of venous thromboembolism
• acute arterial thrombosis
• no preoperative measurement of hemoglobin
• subarachnoid hemorrhage within the past 30 days
• hematuria caused by diseases of the renal parenchyma
• previously enrolled in POISE-3 pilot trial
• not consenting to participate in POISE-3 pilot trial prior to surgery
• Patients meeting any of the following criteria will be excluded from the Rosuvastatin/Placebo arm:
• preoperative treatment with a statin or a non statin lipid lowering drug or ciclosporin during the 48 hours before surgery
• hypersensitivity or known allergy to Rosuvastatin
• pre-disposed factors for myopathy or rhabdomyolysis

Sponsors & Collaborators

• McMaster University: lead
• Population Health Research Institute: collaborator
• Hamilton Health Sciences Corporation: collaborator

Study Sites (2)

Hamilton General Hospital

Hamilton, Ontario, L8L 2X2, Canada

Location

Juravinski Hospital

Hamilton, Ontario, L8V 1C3, Canada

Location

Related Publications (1)

• Marcucci M, Duceppe E, Le Manach Y, Kearon C, Eikelboom JW, Pohl K, Vincent J, Darvish-Kazem S, Srinathan SK, Neary JDD, Parlow JL, Kurz A, Gross PL, Mrkobrada M, Balasubramanian K, Sessler DI, Devereaux PJ. Tranexamic acid and rosuvastatin in patients at risk of cardiovascular events after noncardiac surgery: a pilot of the POISE-3 randomized controlled trial. Pilot Feasibility Stud. 2020 Jul 21;6:104. doi: 10.1186/s40814-020-00643-9. eCollection 2020.

  PMID: 32699643 DERIVED

MeSH Terms

Interventions

Tranexamic Acid; Rosuvastatin Calcium

Intervention Hierarchy (Ancestors)

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

Study Officials

• James Khan, MD

  Hamilton Health Sciences Corporation

  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: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2015
• First Posted: September 11, 2015
• Study Start: February 1, 2015
• Primary Completion: October 1, 2015
• Study Completion: August 1, 2016
• Last Updated: April 24, 2018

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)