Please select the eligibility criteria that correspond to the clinical trial below.
Title: PeriOperative ISchemic Evaluation-3 Trial
Brief Summary: This study is a multicentre, international, randomized controlled trial of tranexamic acid (TXA) versus placebo and, using a partial factorial design, of a perioperative hypotension-avoidance versus hypertension-avoidance strategy.


Options:
A: Inclusion Criteria:

* Male and female patients, of any race, 18 years or older.
* Patients who have at least one bleeding site within the operative field that is mild (oozing or capillary bleeding) to moderate (gradual or steady bleeding) in intensity and which cannot be managed by surgical modalities because they are ineffective or impractical (Change 15, Amend 1).
* Patients scheduled for any of the following elective surgical procedures:

  1. Cardiovascular Procedures - aortic surgery such as aneurysmectomy, aneurysmoplasty, aneurysmorrhaphy, aneurysmotomy and bypass procedures involving the aorta; major coronary bypass procedures including primary bypass surgery and re-do procedures. Peripheral vascular procedures to include femoral-popliteal bypass, femoral-femoral bypass, or other peripheral vascular procedures requiring vessel grafting with native or prosthetic grafts including Polytetrafluoroethylene (PTFE) grafts; carotid endarterectomies. The sternum is excluded as a Target Site. Bleeding sites evaluated during these procedures may include soft tissues (e.g. mammary bed, retroperitoneal fat/connective tissues and adhesions) and needle hole bleeding of prosthetic graft material (Change 6, Amend 1).
  2. Neurosurgical (spine) Procedures- primary lumbar laminectomy and laminectomy with fusion (fusion must be done after the time to hemostasis assessment). Re-do laminectomy, removal of tumors/lesions during laminectomy, cervical, or thoracic laminectomy procedures will be excluded. Bleeding sites evaluated may include periosteum, bone marrow, venous plexus (Change 7, Amend 1).
  3. General Surgery or Post-Traumatic (hemodynamically stable and non-coagulopathic) procedures: bowel and colon resections, retroperitoneal dissections/resections, and procedures involving the resection of any solid abdominal organ such as a splenectomy, liver resection, nephrectomy, splenorrhaphy, and pancreatectomy. Bleeding sites evaluated may include soft tissues (e.g. bowel mesentery, adhesions, lymph node beds, sacral venous plexus, etc.) and parenchymal organ bleeds (cut surface of resected liver, spleen, etc., excluding cut surface of kidney) (Amendment #2, Change 44). Bowel anastomoses sites will not be included (Change 8, Amend 1).
* Patient, or the patient's legally authorized representative, must provide legally effective informed consent prior to any participation in the study. (Amendment #2, Change 41)

Exclusion Criteria:

* Patients with bleeding diathesis, pathologic coagulopathy, systemic disorders, or autoimmune, immunodeficiency diseases or any other disorder that may interfere with hemostasis.
* Patients who have had a pre-operative laboratory finding that was considered clinically significant (as determined by the Investigator) for CBC (HCT, Hgb, white blood cell differential, platelet count, and Red Blood Cell (RBC) indices (MCH, MCV, MCHC)), prothrombin time (PT), or activated partial thromboplastin time (aPTT).
* Patients who have used anticoagulant, antiplatelet or nonsteroidal anti-inflammatory analgesic (NSAID) within 5 days prior to surgery (the use of ASA or aprotinin is permitted).
* Patients with known antibodies to bovine thrombin preparations.
* Patients receiving an organ transplant (liver, heart, kidney, etc.).
* Patients who are morbidly obese (Body Mass Index \> 35).
* Patients with acute or chronic liver failure (Amendment #2, Change 42).
* Patients with all severe (brisk or forceful) bleeding site(s).
* Patients with an ongoing infection at the operative site.
* Patients who are known alcohol and/or drug abusers.
* Female patients who are pregnant or nursing.
* Patients who have uncontrolled diabetes mellitus (blood glucose levels \>400 mg/dl) as determined by the Investigator based on medical history (Change 14, Admin. Change 2).
* Patients who have participated in another investigational drug or device research within 30 days of enrollment.
B: Inclusion Criteria:

* Patients undergoing noncardiac surgery
* ≥ 45 years of age; either sex.
* Have an expected length of stay ≥ 24 hours
* Fulfill any one of the following 6 criteria:

  * coronary artery disease;
  * peripheral vascular disease;
  * history of stroke due to atherothrombotic disease;
  * hospitalization for congestive heart failure within 3 years of randomization;
  * undergoing major vascular surgery; OR
  * any 3 of the following 7 criteria: scheduled for high risk surgery (i.e. intraperitoneal or intrathoracic); emergency/urgent surgery; any history of congestive heart failure; history of a transient ischemic attack (TIA); diabetes and currently on an oral hypoglycemic agent or insulin therapy; preoperative serum creatinine \> 175 µmol/L (\> 2.0 mg/dl); or age \> 70 years.

Exclusion Criteria:

* Contraindication to metoprolol including any of the following: significant bradycardia (heart rate \< 50 beats per minute); second or third degree heart block without a pacemaker; asthma that has been active within the last decade; and history of chronic obstructive pulmonary disease (COPD) with bronchospasm on pulmonary function tests.
* Clinical plan to use a beta-blocker preoperatively or during the first 30 postoperative days
* Prior adverse reaction to a beta-blocker
* Coronary artery bypass graft (CABG) surgery with complete revascularization in the preceding 5 years and no evidence of cardiac ischemia since the CABG surgery
* Patients undergoing low risk surgical procedures (potential examples include transurethral procedures \[transurethral prostatectomies (TURPs), stone baskets, etc.\], ophthalmologic procedures under topical or regional anesthesia \[cornea transplants, cataract surgery, etc.\], and surgeries with limited physiological stresses \[digital re-implantation, nerve repairs, etc.\] )
* Concurrent use of verapamil
* Prior enrollment in this trial
C: Inclusion criteria:

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 µmol/L (\> 2.0 mg/dl); viii. History of smoking within 2 years of surgery; ix. Undergoing emergent/urgent surgery.

Exclusion 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 month)
9. Patients with fibrinolytic conditions following consumption coagulopathy
10. Patients with subarachnoid hemorrhage within the past 30 days
11. Women of childbearing potential who are not taking effective contraception, pregnant or breast-feeding
12. Previously enrolled in POISE-3 Trial
D: Inclusion Criteria:

* Age \> 50
* Able to give written informed consent
* Undergoing open abdominal aortic aneurysm repair

Exclusion Criteria:

* Patients participating in a pharmaceutical clinical trial in the last 3 months
* Urgent/emergent surgery
* Allergy/intolerance to tranexamic acid
* History of seizures
* Acute Venous or Arterial Thrombosis
* Fibrinolytic conditions due to consumption coagulopathy
* Disseminated intravascular coagulation
* Haematuria
* Visual disturbances

Answer: C