Please select the eligibility criteria that correspond to the clinical trial below.
Title: RiaSTAP vs. Conventional Transfusion for Patients Undergoing Valve Replacement Surgery: RiaCT
Brief Summary: Heart surgery involving valve replacement often involves the use of the heart-lung machine for over 90 minutes, and bleeding tendency is frequently seen. Conventionally, platelet transfusion has been the primary therapy to treat bleeding after this type of procedure. More recently, perioperative supplementation of purified fibrinogen (RiaSTAP, CSL Behring) was shown to reduce bleeding and blood product use (plasma or platelets) after heart surgery. The objective of this trial is to demonstrate the clinical equivalency and economic utility of using fibrinogen concentrate, RiaSTAP for the mitigation of post-operative bleeding in patients in lieu of platelet transfusion.

Purified fibrinogen concentrate has been approved by FDA, and it has been used for the treatment of acute bleeding episodes in patients with low fibrinogen due to hereditary causes (e.g., afibrinogenemia). Compared to the transfusion of platelets which may be associated with volume overload, bacterial/viral infection, immunological effects and excess blood clotting, purified fibrinogen has several advantages. First, it contains no liquid plasma allowing for low volume infusion. Several viral inactivation/reduction steps are used to prepare the fibrinogen concentrate, increasing its viral safety. No antibodies or white blood cells are contained in the fibrinogen concentrate; therefore transfusion reactions are rare. Although platelet transfusion is widely used after heart surgery, there has been no randomized study to endorse this practice. In this study, patients undergoing heart valve replacement will be randomized to receive either platelet (1 unit) transfusion or fibrinogen concentrate (4g) after heparin anticoagulation is reversed. Subjects will be treated only if there is evidence of significant microvascular bleeding. Fifteen minutes after the initial treatment, subjects will be reevaluated for bleeding. If bleeding continues, subjects will be treated with blood transfusion per institutional standard of care.

The primary endpoints for this study are the hemostatic condition of the surgical field and 24-hour total of blood product transfusion.


Options:
A: Inclusion Criteria:

* Chronic liver failure (cirrhosis or chronic graft dysfunction) from any cause and medical indication of central venous line placement

Exclusion Criteria:

* Acute liver failure or
* Use of therapeutic doses of oral or parenteral anticoagulants (unfractionated heparin or low molecular weight heparin or oral anticoagulants) or
* Use of oral or parenteral platelet aggregation inhibitors or
* Patients with von Willebrand syndrome or
* Over-the-guidewire central venous catheter changing
* Patients previously included in this study protocol during the same hospital stay
B: Inclusion Criteria:

* Male and female subjects, 18 years of age or more with chronic liver disease.
* Child-Pugh score of 12 or less.
* Model of End Stage Liver Disease (MELD) score of 24 or less.
* Subjects who, in the opinion of the investigator, are appropriate candidates to undergo an elective invasive procedure and who require a platelet transfusion to manage the risk of bleeding associated with the procedure.
* A baseline platelet count \<50,000/µL.
* A baseline serum sodium level \>130mEq/L.
* Haemoglobin concentration \>8g/dL stable for at least one month.
* A female is eligible to enter and participate in the study if she is of:

Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) including any female who:

* Has had a hysterectomy
* Has had a bilateral oophorectomy (ovariectomy)
* Has had a bilateral tubal ligation
* Is post-menopausal (demonstrate total cessation of menses for greater than one year)

Childbearing potential, has a negative urine and/or serum pregnancy test at screening, and within the 24 hour period prior to the first dose of investigational product and uses one of the following acceptable methods of contraception:

* Complete abstinence from intercourse for two weeks before exposure to the study drug, throughout the clinical study, and for 28 days after completion or premature discontinuation from the study to account for the elimination of the study drug (minimum of 5 half-lives).
* Any intrauterine device (IUD) with a documented failure rate of less than 1% per year.
* Double-barrier contraception (condom with spermicidal jelly, or diaphragm with spermicide).
* Male partner who is sterile (diagnosed by a qualified medical professional) prior to the female subject's study entry and is the sole sexual partner for that female.
* Oral contraceptive (either combined or progesterone only).
* Any other contraceptive method with a documented failure rate of \<1% per year.
* Subject has no physical limitation to ingest and retain oral medication.
* Subject is able to understand and comply with protocol requirements and instructions and is likely to complete the study as planned.
* Subject is able to provide signed and dated written informed consent.
* In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

* Subjects with a known hypersensitivity, intolerance or allergy to any of the ingredients in eltrombopag tablets.
* Evidence of portal vein thrombosis on abdominal imaging (ultrasound with Doppler or appropriate MRI/CT imaging techniques) within 3 months of study start.
* History of arterial or venous thrombosis, including Budd-Chiari Syndrome, AND ≥ two of the following risk factors: hereditary thrombophilic disorders (e.g. Factor V Leiden, ATIII deficiency, etc.), hormone replacement therapy, systemic contraception therapy (containing oestrogen), smoking, diabetes, hypercholesterolemia, medication for hypertension or cancer.
* Any disease condition associated with current active WHO Grade 3 or 4 bleeding.
* Active infection requiring systemic antibiotic therapy. Prophylactic use of antibiotics is permitted.
* Pregnant or nursing women.
* Treatment with an investigational drug within 30 days or five half-lives (whichever is longer) preceding the first dose of study medication.
* History of platelet agglutination abnormality that prevents reliable measurement of platelet counts.
* History of porphyria.
* Previous participation in TPL104054.
C: Hospital Inclusion:

* Participating hospitals must not currently be using a POC-based blood conservation algorithm; must have an in-hospital RBC transfusion rate of \> 35% and platelet or plasma transfusion rates of \> 20%; must conduct \> 600 cardiac surgeries employing CPB per year; and must have commitments from departments of Anesthesia, Cardiac Surgery, and Laboratory Medicine to support the study and to abide by the algorithm
* Blood transfusion algorithm instituted as standard-of-care at participating hospitals
* All adult (≥ 18 years) patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) will be included in the analysis.

Exclusion Criteria: Hospitals not meeting inclusion.
D: Inclusion Criteria:

* Willing and able to provide written informed consent
* Age \>17 and \< 86 years
* Patients undergoing planned cardiopulmonary bypass (CPB) for:

  1. combined coronary artery bypass grafting and valve replacement/repair surgery
  2. single valve replacement surgery
  3. mitral valve repair surgery

  3. or double valve surgery (aortic and mitral)
* Presence of clinically relevant microvascular bleeding after protamine administration (hemostasis assessment score of 2-3)
* Patients should fulfill the following parameters prior to the study intervention:

  * Body temperature \> 35.0°C
  * Blood pH \> 7.2
  * Hb \> 7.0 mg/dL
  * Activated clotting time (ACT) \< 155 seconds
  * CPB time \> 60 minutes

Exclusion Criteria:

* Replacement of aorta
* Planned valve replacement without median sternotomy
* Previous valve replacement surgery (previous coronary artery bypass graft (CABG) acceptable)
* History or suspicion of a congenital or acquired coagulation disorder such as hemophilia, von Willebrand disease, and liver disease
* Hemodialysis dependent renal failure
* Liver dysfunction (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) increased ≥ 2-fold above the upper limit of local laboratory normal ranges)
* Known allergy/anaphylaxis to fibrinogen concentrate or apheresis platelet units
* Clopidogrel administration within 5 days of surgery
* Coumadin (warfarin) administration within 5 days of surgery
* Participation in another clinical study in the 4 weeks preceding surgery
* Any indication that a potential subject did not comprehend the study restrictions, procedures, or consequences therein an informed consent cannot be convincingly given
* Life expectancy less than 48 hours

Answer: D