The occurrence of life-threatening, major, and critical organ bleeding, and, major arterial and venous thrombosis in patients undergoing noncardiac surgery. And for patients in the blood pressure management factorial, the occurrence of vascular death and major vascular events. MedDRA version: 20.0 Level: LLT Classification code 10043611 Term: Thrombosis arterial System Organ Class: 100000004866 MedDRA version: 21.0 Level: LLT Classification code 10043640 Term: Thrombosis venous System Organ Cl
Conditions
Interventions
Trade Name: Cyklokapron, oplossing voor injectie 100 mg/ml (Tranexamic Acid)
Product Name: Tranexamic acid
Pharmaceutical Form: Injection
INN or Proposed INN: TRANEXAMIC ACID
CAS Number: 1197-18-8
Oth
Sponsors
Hamilton Health Sciences Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients are eligible if they fulfill all of the following criteria: 1. =45 years of age; 2. expected to require at least an overnight hospital admission after noncardiac surgery; 3. provide written informed consent to participate in POISE-3; AND 4. have a preoperative NT-pro-BNP measurement =200 ng/L; OR 5. if a preoperative NT-pro-BNP measurement is not available, then the patient must fulfill =1 of the following 5 criteria: A. history of coronary artery disease; B. history of peripheral arterial disease; C. history of stroke; D. undergoing major vascular surgery; E. any 3 of the following 9 criteria: undergoing major surgery (i.e. intraperitoneal, intrathoracic, retroperitoneal, or major orthopedic surgery), history of congestive heart failure, transient ischemic attack, diabetic and currently taking an oral hypoglycemic agent or insulin, age >70 years, hypertension, serum creatinine >175 µmol/L (>2.0 mg/dl), history of smoking within 2 years of surgery, undergoing urgent/emergent surgery. Additionally, patients will be considered eligible for the BP partial factorial if they have been chronically receiving =1 antihypertensive medication. Patients will be eligible for inclusion in the cogPOISE-3 substudy if they are enrolled in both the TXA and blood pressure management arms of the POISE-3 trial. cogPOISE-3 patients will be included in the cognitive assessment part of the substudy if they consent to the assessment of their cognitive performance at baseline (i.e., within 30 days prior to randomization) and at 1 year after randomization. Patients with a documented history of dementia will not be eligible for the cognitive assessment part of the substudy. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 3000 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 7000
Exclusion criteria
Exclusion criteria: We will exclude patients meeting any of the following criteria: 1. Patients undergoing cardiac surgery 2. Patients undergoing cranial neurosurgery 3. Planned use of systemic TXA during surgery 4. Low-risk surgical procedure (based on individual physician's judgment) 5. Hypersensitivity or known allergy to TXA 6. Creatinine clearance <30 mL/min (Cockcroft-Gault equation) or on chronic dialysis 7. History of seizure disorder 8. Patients with recent stroke, myocardial infarction, acute arterial thrombosis or venous thromboembolism (<3 months) 9. Patients with fibrinolytic conditions following consumption coagulopathy 10. Patients with subarachnoid hemorrhage within the past 30 days XML File Identifier: GAzUEh+LNMtCuWOAjWv53n5aWVg= Page 11/21 11. Women of childbearing potential who are not taking effective contraception, pregnant or breast-feeding 12. Previously enrolled in POISE-3 Trial Additionally, patients will be excluded for the BP partial factorial if: 1. Patients with advanced congestive heart failure (New York Heart Association functional class III or IV or left ventricular ejection fraction =30%), 2. Patients with untreated brain aneurysm, 3. Patients with previous history of hypertensive related cerebral hemorrhage, 4. Patients undergoing surgery for pheochromocytoma or history of untreated pheochromocytoma, 5. Patients who are hemodynamically unstable or requiring vasopressors or inotropic support before undergoing surgery. 6. Patients with thyrotoxicosis (i.e., severe hyperthyroidism) requiring perioperative beta-blocker therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine if TXA is superior to placebo for the occurrence of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic events; and to determine the impact of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of vascular death and major vascular events in patients who are followed for 30 days after noncardiac surgery.;Secondary Objective: To determine the impact of TXA on the following outcomes at 30 days after randomization: a net risk-benefit outcome as a composite of vascular death, and nonfatal life-threatening bleeding, and nonfatal major bleeding, critical organ bleeding, myocardial injury after noncardiac surgery (MINS), stroke, peripheral arterial thrombosis, and symptomatic venous thromboembolism; International Society on Thrombosis and Haemostasis (ISTH) major bleeding; bleeding independently associated with mortality after noncardiac surgery (BIMS); MINS; MINS not fulfilling the 3rd universal definition of myocardial infarction (MI); and myocardial infarction. To determine the impact of a perioperative hypotension-avoidance strategy on all-cause mortality; MINS; and myocardial infarction at 30 days after randomization.;Primary end point(s): The co-primary efficacy outcome for TXA trial is a composite of lifethreatening bleeding, major bleeding, and critical organ bleeding at 30 days after randomization. The co-primary safety outcome for TXA trial is a composite of myocardial injury after noncardiac surgery, non-hemorrhagic stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism at 30 days after randomization. The primary outcome for the BP management trial is a composite of vascular death, and non-fatal myocardial injury after noncardiac surgery, non-fatal stroke, and non-fatal cardiac arrest at 30 days after randomization.;Timepoint(s) of evaluation of this end point: 30 days and 1 year | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary outcomes for TXA trial are: 1) a net risk-benefit outcome as a composite of vascular death, and non-fatal life-threatening, major or critical organ bleeding, myocardial injury after noncardiac surgery, stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism at 30 days after randomization; 2) International Society on Thrombosis and Haemostasis (ISTH) major bleeding; 3) BIMS; 4) MINS; 5) MINS not fulfilling the 3rd universal definition of myocardial infarction and 6) myocardial infarction at 30 days after randomization. The secondary outcomes for the BP management factorial are: 1) allcause mortality at 30 days after randomization; 2) MINS; and 3) myocardial infarction at 30 days after randomization. ;Timepoint(s) of evaluation of this end point: 30 days and 1 year after randomization | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Denmark, France, Germany, Hong Kong, India, Ireland, Italy, Netherlands, New Zealand, Poland, Romania, Saudi Arabia, South Africa, Spain, Switzerland, Uganda, United Kingdom, United States
Contacts
Public ContactPOISE-3 Project Office
Population Health Research Institute
Outcome results
None listed