Please select the eligibility criteria that correspond to the clinical trial below.
Title: REPLACE (Randomized Evaluation of Fibrinogen Versus Placebo in Complex Cardiovascular Surgery): a Prospective, Multinational, Multicenter, Randomized, Double-blind, Placebo-controlled, Phase III Study for the Use of Fibrinogen Concentrate (Human) (FCH) in Complex Cardiovascular Surgery
Brief Summary: The purpose of this study is to demonstrate that Fibrinogen Concentrate (Human)(FCH) can reduce the amount of donor blood products needed during complex cardiovascular surgery, and that it is safe and well tolerated. Subjects in this study will get either a FCH or placebo infusion during surgery. This will be in addition to the standard treatment, which is donor blood or blood products. Placebo does not contain any effective medicine.

The study is randomised. This means that the likelihood that subjects will get FCH or placebo is 50%. To make the comparison between FCH and placebo as fair as possible, the study is "double blind". This means that neither the subjects nor the study doctor will know if FCH or placebo is administered. If necessary, the study doctor can find out which treatment the subjects are receiving.


Options:
A: 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).
B: Inclusion Criteria:

* Eighteen years of age or older
* Undergoing elective thoracoabdominal aortic replacement surgery (TAAA) or thoracic aortic replacement surgery (TAA)
* Understood and willingly given written informed consent (German language) to participate following an explanation of study background, restrictions, and procedures
* Experience clinically relevant bleeding of the microvasculature following removal of CPB during surgery

Exclusion Criteria:

* Positive pregnancy test, pregnancy or lactation
* Women of child bearing age not using a medically approved method of contraception during the study
* Previous aortic replacement at the same aortic site (redo surgeries)
* Undergoing an emergency operation
* Proof or suspicion of a congenital or acquired coagulation disorder (e.g. VWD or via severe liver disease)
* Myocardial Infarction (MI) or apoplexy in the 2 months preceding study surgery
* ASA administration in the 3 days preceding study surgery, and a pathological (\<74.5 U) ASPI Multiplate® test immediately preceding surgery begin
* Clopidogrel administration in the 5 days preceding study surgery, and a pathological (\<31.1 U) ADP/PG Multiplate® test immediately preceding surgery begin
* Tirofiban administration in the 2 days preceding study surgery, and a pathological (\<94.1 U) TRAP Multiplate® test immediately preceding surgery begin
* Phenprocoumon administration in the 5 days preceding study surgery, and an INR \> 1.28 immediately preceding surgery begin
* Participation in another clinical study in the 4 weeks preceding aortic replacement
* Sensitivity to any of the components of study medication, or to MPs with a similar chemical structure to any of the components of study medication
* Any indication that the restrictions or procedures of the study may not be adhered to (e.g. an uncooperative attitude)
* Any indication that the study restrictions, procedures, or consequences therein have not been considered or understood, such that informed consent cannot be convincingly given
* Multiple morbidities, with a notably constrained remaining length of life
C: 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
D: Inclusion Criteria:

At Screening:

* Undergoing elective open surgical procedures on any part of the aorta requiring cardiopulmonary bypass (CPB), with or without other cardiac surgical procedures (e.g. valve replacement or repair, coronary artery bypass grafting, etc.).
* 18 years of age or older.
* Written informed consent for study participation obtained before undergoing any study specific procedures.

Intraoperative (at the 1st 5-minute bleeding mass):

* A 5-minute bleeding mass of 60 to 250 g following discontinuation of CPB, administration of protamine, and establishment of surgical hemostasis.
* Minimum core body temperature 35°C, measured according to local practice.
* Activated clotting time ± 25% of baseline levels.
* Blood pH \> 7.3.

Exclusion Criteria:

At Screening and/or baseline:

* Undergoing emergency aortic repair surgery.
* Reoperative aortic surgery at the same anatomic site as the original procedure such as replacement of a previously placed aortic graft. Resternotomy and rethoracotomy are permitted.
* Any operation for infection.
* Proof or suspicion of a congenital or acquired coagulation disorder (e.g. Von Willebrand's disease, hemophilia or severe liver disease) or a prothrombotic disorder (e.g. protein C or S deficiency).
* Myocardial infarction (MI), acute coronary syndrome or stroke in the 2 months preceding study surgery.
* Low molecular weight or unfractionated heparin in the 24 hours preceding study surgery.
* Clopidogrel administration within 5 days preceding study surgery or prasugrel administration within 7 days preceding study surgery or ticagrelor administration in the 48 hours preceding study surgery.
* Factor Xa inhibitors within 2 days preceding study surgery.
* IIb/IIIa antagonist administration in the 24 hours preceding study surgery.
* Use of direct thrombin inhibitors: within 3 days preceding study surgery for dabigatran and within 24 hours preceding study surgery for all others.
* An international normalized ratio \> 1.3 immediately preceding the start of surgery.

Intraoperative (at the 1st 5-minute bleeding mass):

* Use of any systemic hemostatic therapy (such as FFP, platelets, prothrombin complex concentrates) from the beginning of surgery until IMP administration.

Answer: D