Please select the eligibility criteria that correspond to the clinical trial below.
Title: The ZEroPLASmaTrial (ZEPLAST): a Randomized, Controlled Trial on Transfusion Avoidance in High Transfusion-risk Cardiac Surgery Patients
Brief Summary: Prospective, randomized, double blind trial. The rationale of the study is the concept that fresh frozen plasma (FFP) is still largely used in cardiac surgery, despite the fact that prothrombin complexes and fibrinogen are available.The experimental hypothesis is that cardiac surgery patients may be operated with no use of FFP and with a coagulation factors replacement based on fibrinogen and prothrombin complexes (when needed).

Primary endpoint: Transfusion avoidance Secondary endpoints: Transfusion limitation, massive blood transfusion, bleeding.

Study population: high-risk adult cardiac surgery patients Sample size : 2 groups of 60 patients each


Options:
A: Inclusion Criteria:

* Male and female subjects greater than or equal to 18 years,
* Subjects currently on oral vitamin K antagonist (VKA) therapy,
* An urgent surgical procedure is required within 24 hours of the start of investigational medicinal product (IMP),
* Due to the nature of the procedure, withdrawal of oral VKA therapy and infusion of plasma are also indicated to reverse the VKA effect,
* INR greater than or equal to 2 within 3 hours before start of IMP,
* Informed consent has been obtained.

Exclusion Criteria:

* Subjects requiring urgent surgical procedures where according to the surgeon's clinical judgment, an accurate estimate of blood loss is not possible (e.g., ruptured aneurysm),
* Subjects for whom administration of intravenous vitamin K and vitamin K antagonists withdrawal alone can adequately correct the subject's coagulopathy before initiation of the urgent surgical procedure,
* Administration of intravenous vitamin K more than 3 hours or administration of oral vitamin K more than 6 hours prior to infusion of IMP,
* Subjects in whom lowering INR within normal range may present an unacceptable risk for a thromboembolic complication where the INR goal is to lower but not normalize the INR because of risk of a procedure-associated stroke,
* Subjects, who despite medical management that includes close monitoring and diuretics, may not, by investigator assessment, tolerate the total volume of IMP required by the protocol,
* Expected need for additional non-study blood products before infusion of IMP (Note: Administration of packed red blood cells is not an exclusion criterion),
* Expected need for platelet transfusions or desmopressin before Day 10,
* Acute trauma for which reversal of vitamin K antagonists alone would not be expected to control or resolve an acute bleeding complication and/or control the acute bleeding event,
* Unfractionated or low molecular weight heparin use within 24 hours before randomization or potential need before completion of the procedure,
* History of thromboembolic event, myocardial infarction, unstable angina pectoris, critical aortic stenosis, cerebral vascular accident, transient ischemic attack, severe peripheral vascular disease, disseminated intravascular coagulation within 3 months of enrollment,
* Reversal of VKA therapy alone may not resolve the coagulopathy (eg, receiving a potent anti-platelet agent, i.e., clopidogrel or prasugrel, or advanced liver disease),
* Known history of antiphospholipid antibody syndrome or lupus anticoagulant antibodies,
* Suspected or confirmed serious viral or bacterial infection, e.g., meningitis, or sepsis at time of enrollment,
* Administration of whole blood, plasma, plasma fractions or platelets within 2 weeks prior to inclusion into the study (Note: Administration of packed red blood cells is not an exclusion criterion),
* Pre-existing progressive fatal disease with a life expectancy of less than 2 months,
* Known inhibitors to coagulation factors II, VII, IX, or X; or hereditary protein C or protein S deficiency; or heparin-induced, type II thrombocytopenia,
* Treatment with any other investigational medicinal product within 30 days prior to inclusion into the study,
* Presence or history of hypersensitivity to components of the study medication,
* Pregnant or breast-feeding women,
* Prior inclusion in this study or any other CSL Behring sponsored Beriplex study,
* For subjects with intracranial hemorrhage with:

  * Glasgow Coma Score \<10 (see Appendix 8)
  * Modified Rankin Score \> 3 prior to ICH (see Appendix 9)
  * Intracerebral hemorrhage
  * Epidural hematomas
  * Infratentorial hemorrhage
  * Subarachnoid hemorrhage (SAH) subjects with a Hunt and Hess Scale \>2
  * Subdural hematomas that:

    * are judged to be an acute subdural hematoma (based on neurosurgeon review)
    * have a concurrent SAH or parenchymal contusion
B: Inclusion Criteria:

* - Planned coronary artery bypass grafting (CABG) or CABG plus single heart valve replacement/repair or planned replacement/repair of a single heart valve

Exclusion Criteria:

* Known intolerance to protamine
* Known or suspected allergy to the used antifibrinolytic agent
* Refusal to receive blood or blood product
* Planned surgery including the aortic arch and/or descending aorta
* Planned surgery including any implantable ventricular assist device
* Adult congenital heart diseases
* Two or more previous cardiac surgery procedures
* Any known autoimmune diseases: Collagen vascular disease (Systemic lupus erythematosus, Rheumatoid arthritis, Sjögrens syndrome) - Endocrine: hyperthyroidism (Graves disease), adrenal insufficiency, Hashimoto's thyroiditis - Neurologic: Multiple sclerosis, myasthenia gravis - Skin: pemphigous vulgaris Hematologic: Pernicious anaemia, Autoimmune haemolytic anaemia - Vasculitis - Primary or secondary antiphospholipid syndrome
* Weight above 140 kg
C: Inclusion Criteria:

* The patients will be screened according to a modified TRUST1 Transfusion Score. This score attributes 1 point to each of the following conditions:

  * Hb level \< 13.5 g/dL
  * Weight \< 77 kg
  * Female sex
  * Age \> 65 years
  * Non elective surgery
  * Serum creatinine \> 1.36 mg/dL
  * Redo operation
  * Non isolated surgery
  * Factors are hemodilution-related factors, and will not be included. Non isolated surgery is mandatory for inclusion. Patients will be included in presence of at least 1 within the remaining 4 risk factors:
  * Age \> 65 years
  * Non elective surgery
  * Serum creatinine \> 1.36 mg/dL '8Redo operation INCLUSION CRITERIA (patients randomized)

    1. Combined cardiac operation with expected CPB duration \> 90 minutes
    2. At least one additional risk factor within the following: Age \> 65 years; Non elective surgery; Serum creatinine \> 1.36 mg/dL; Redo operation

Exclusion Criteria:

1. Age \< 18 years
2. Patients under thienopyridines
3. Known coagulopathy
4. Known autoimmune disorders
5. Participation in another RCT
6. Pregnancy
7. Emergency operation
8. Baseline HCT \< 35%
9. Baseline Antithrombin \< 80%
10. BSA \< 1.7 m2

WITHDRAWAL CRITERION:

1. Lowest HCT on CPB \< 23%
2. Transfusions during CPB

   * Patients randomized and not withdrawn will be DOSED with the investigational drugs.
D: Inclusion Criteria:

* Eighteen years of age or older.
* Undergoing elective complex cardiac surgery.
* Understood and willingly given written informed consent.
* Experience clinically relevant non-surgical microvascular bleeding following removal of cardiopulmonary bypass.

Exclusion Criteria:

* Positive pregnancy test, pregnancy or lactation.
* Undergoing an emergency operation.
* Proof or suspicion of a congenital or acquired coagulation disorder.
* Clopidogrel use in the 5 days preceding surgery.
* INR \>1.4 if on coumadin.

Answer: C