â??Evaluation of tranexamic acid compared with placebo among patients with or at risk of heart disease undergoing surgeries not related to the heart, on bleeding and blood vessel occlusive outcomes

Phase 3

Conditions: Health Condition 1: I95-I99- Other and unspecified disorders of the circulatory system

Registration Number: CTRI/2019/06/019833

Lead Sponsor: Population Health Research Institute

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Open to Recruitment

Sex: Not specified

Target Recruitment: 0

Inclusion Criteria

Patients need to meet the following criteria for inclusion

1. Undergoing noncardiac surgery;

2. >= 45 years of age;

3. Expected to require at least an overnight hospital admission after surgery;

4. Provide written informed consent to participate in the POISE-3 Trial, AND

5. Fulfill >=1 of the following 6 criteria (A-F):

A. NT-proBNP >=200 ng/L

B. History of coronary artery disease

C. History of peripheral arterial disease

D. History of stroke

E. Undergoing major vascular surgery; OR

F. Any 3 of 9 risk criteria

i. Undergoing major surgery;

ii. History of congestive heart failure;

iii. History of a transient ischemic attack;

iv. Diabetes and currently taking an oral hypoglycemic agent or insulin;

v. Age >=70 years;

vi. History of hypertension;

vii. Serum creatinine > 175 Î¼mol/L ( > 2.0 mg/dl);

viii. History of smoking within 2 years of surgery;

ix. Undergoing emergent/urgent surgery.

INCLUSION CRITERIA SPECIFIC TO PATIENTS IN THE BP MANAGEMENT FACTORIAL COMPONENT OF THE TRIAL

For inclusion in the hypotension-avoidance strategy group vs. hypertension-avoidance strategy group, patients are also required to fulfill the following criteria:

1.Treated chronically (i.e., at least 30 days in the 6 weeks preceding randomization), with at least one antihypertensive medication of any class (i.e., ACEIs, ARBs, renin inhibitors, Î²-blockers, calcium channel blockers [CCBs], central Î±2-agonists, Î±-blockers, direct vasodilators long-acting nitrates, thiazide diuretics, and potassium sparing diuretics)

2. Provide written consent to participate in the partial factorial BP management trial

Exclusion Criteria

We will exclude patients meeting any of the following criteria

1. Planned use of systemic TXA during surgery

2. Hypersensitivity or known allergy to TXA

3. Creatinine clearance <30 mL/min (Modification of Diet in Renal Disease [MDRD])

4. History of seizure disorder

5. Patients with recent stroke, myocardial infarction, acute arterial thrombosis or venous thromboembolism ( <1 month)

6. Patients with subarachnoid hemorrhage within the past 30 days

7. Patients undergoing cranial neurosurgery

8. Previously enrolled in POISE-3 Trial

EXCLUSION CRITERIA SPECIFIC TO PATIENTS IN THE BP MANAGEMENT FACTORIAL COMPONENT OF THE TRIAL

Patients meeting any of the following criteria will be excluded:

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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Efficacy and safety endpoints - life-threatening bleeding, major bleeding, and critical organ bleeding, myocardial infarction, non-hemorrhagic stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism <br/ ><br> <br/ ><br>Outcomes for BP management component of trial are vascular death, non-fatal myocardial infarction, stroke, and cardiac arrestTimepoint: Evaluated during/at 30 days after randomization

Secondary Outcome Measures

Name	Time	Method
The secondary outcomes are: 1) a net risk-benefit outcome as a composite of vascular death, and non-fatal life-threatening; major or critical organ bleeding, myocardial infarction, stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism; 2) International Society on Thrombosis and Haemostasis (ISTH) major bleeding; 3) BIMS; 4) MINS; 5) myocardial infarction <br/ ><br> <br/ ><br>BP management outcomes are: 1) all-cause mortality and MI at 30 days after randomization; and 2) MINSTimepoint: Evaluated during and at 30 days after randomization