Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Prospective, Randomized, Double-blind, Phase II Study to Evaluate the Safety and Efficacy of Topical Thrombin (Human) Grifols as an Adjunct to Hemostasis During Vascular, Hepatic, Soft Tissue, and Spinal Open Surgeries
Brief Summary: This purpose of this clinical trial was to study the safety and efficacy of Topical Thrombin (Human) Grifols as an add-on treatment to help stop bleeding during vascular, liver, soft tissue, and spinal surgical procedures.


Options:
A: 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
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. Has signed an institutional review board/independent ethics committee (IRB/IEC)-approved informed consent document
2. Is undergoing one of the 4 surgical procedures described
3. Is at least 18 years old at time of consent
4. If female and of child-bearing potential, has negative pregnancy test during screening and is not breast-feeding
5. If able to reproduce, agrees to use a medically accepted form of contraception from the time of consent to completion of all follow-up study visits when engaging in heterosexual intercourse
6. Has not received blood transfusion between screening and study treatment
7. Has mild to moderate surgical bleeding
8. Does not have intra-operative complications
9. Has not used a topical hemostat containing thrombin prior to study treatment
10. Has an approximate bleeding site surface area of less than or equal to 100 cm\^2

Exclusion Criteria:

1. Has known antibodies or hypersensitivity to thrombin or other coagulation factors
2. Has history of heparin-induced thrombocytopenia (only for vascular subjects where heparin use is required)
3. Has known allergy to gelatin sponge
4. Is unwilling to receive blood products
5. Has liver enzymes appropriate for the study, considering their disease
6. Has appropriate level of platelets per liter (PLT/L) during screening
7. Has any clinically-significant coagulation disorder that may interfere with the assessment of efficacy or pose a safety risk to the subject according to the Investigator, or baseline abnormalities during screening that are not explained by current drug treatment (e.g., warfarin, heparin)
D: Inclusion Criteria:

* Pre-operative (at Baseline Assessments Visit) hemoglobin (Hgb) ≥9.0 g/dL (deciliter)
* Pre-operative (at Baseline Assessments Visit) fibrinogen level ≥150 mg/dL (functional method).
* Required one of the following procedures:

  1. An elective (non-emergency), open (non-laparoscopic; non- endovascular) surgical procedure involving a native artery-graft end-to-side proximal anastomosis utilizing coated or uncoated polytetrafluoroethylene (PTFE) graft (IG1202-A).
  2. An elective (non-emergency), open (non-laparoscopic) hepatic resection (anatomic and non-anatomic resections of at least one anatomical hepatic segment or equivalent tissue volume) (IG-1202-B).
  3. An elective (non-emergency), open (non-laparoscopic), surgical procedure involving soft (non-parenchymous) tissue (IG1202-C).
  4. An elective (non-emergency), spinal surgical procedure in which the epidural venous plexus was exposed (IG1202-D).
* A target bleeding site (TBS) was identified according to the Investigator's judgment, and the TBS had mild or moderate bleeding according to the Investigator's judgment.

Exclusion Criteria:

* Required surgical procedure due to trauma (except for spinal surgery).
* Infection in the anatomic surgical area.
* History of severe (e.g. anaphylactic) reactions to blood or to any blood-derived (human or animal) product.
* Previous known sensitivity to any Topical Thrombin (Human) Grifols component, any Bovine Thrombin JMI component, porcine collagen, and heparin or protamine (vascular surgery only) component.
* Received an organ transplant.
* Underwent another concurrent major surgical intervention beyond the liver (applied to hepatic surgery \[IG1202-B\] only; concurrent interventions on the pancreas, gall bladder, bile duct, or intestines were allowed).
* Underwent a re-operative procedure, which was defined as a second, or successive, surgical procedure on the same anatomic location.
* Underwent other vascular procedures during the same surgical session (applied to vascular surgery \[IG1202-A\] only; stenting and/or endarterectomy of the same artery were allowed).
* Underwent a therapeutic surgical procedure within 30 days from screening (diagnostic procedures were allowed).
* Previously included in this trial (i.e. each subject could only be enrolled once in this study).
* TBS could not be identified according to the investigator's judgment.
* TBS had a severe bleeding according to the Investigator's judgment.
* Occurrence of major intra-operative complications that required resuscitation or deviation from the planned surgical procedure.
* Application of any topical haemostatic material on the resection surface of the liver prior to application of the study treatment (applied to hepatic surgery \[IG1202-B\] only).
* Radiofrequency precoagulation of the liver resection surface, except focal use of radiofrequency as primary haemostatic treatment (applied to hepatic surgery \[IG1202-B\] only).
* Intra-operative change in planned surgical procedure which resulted in subject no longer meeting preoperative inclusion and/or exclusion criteria.
* Application of any topical haemostatic material on the cut soft tissue surface prior to application of the study treatment (applied to soft tissue surgery \[IG1202-C\] only).

Answer: D