Trial of RiaSTAP Versus Cryoprecipitate to Lower Operative Transfusions

All eligible subjects undergoing cardiac surgery requiring cardiopulmonary bypass (CPB) at
New York Presbyterian Hospital-Weill Cornell Medical College will be invited to participate.
Consenting subjects will be enrolled and treated according to the protocol. Study
investigators anticipate that by consenting all eligible cardiovascular surgical subjects,
investigators will not omit the results of subjects who may present with microvascular
bleeding after CPB. It is well known that microvascular bleeding occurs more often in
reoperations or complex, open cardiac procedures, such as coronary revascularization and
valve repair/replacement, or aortic replacements under deep hypothermic circulatory arrest.

Enrolled subjects will receive intraoperative anesthetic, anticoagulation, laboratory
testing, and hemodynamic management according to WCMC standards of practice. The need for
blood products, including fibrinogen supplementation (CRYO/FIB), will be assessed using a
point-of-care (ROTEM) based transfusion algorithm (Appendix A) to ensure consistency and
accuracy of treatment. The cardiac anesthesiologists and surgeons are currently using the
ROTEM algorithm for the treatment of bleeding during cardiovascular surgery with CPB as part
of routine clinical practice at WCMC. The algorithm will have been in place for greater than
9 months prior to study initiation. Randomization will occur in the blood bank when study
product (CRYO/FIB) is requested to treat intraoperative acquired hypofibrinogenemia (based on
ROTEM tracings). Transfusion of the randomized study product (CRYO/FIB), however, will only
occur when the surgeon declares the presence of microvascular bleeding. Surgeons will be
blinded to the subject's ROTEM results and randomized study arm. Intraoperative
anesthesiologists will not be blinded as the two products require different preparation and
administration techniques and cannot be blinded easily.

Once the subject is randomized to their study intervention they will receive that product at
all subsequent points during the procedure when fibrinogen replacement is required. If
microvascular bleeding occurs and there is no indication by the ROTEM algorithm to administer
CRYO/FIB, the subject will revert to standard of care treatment guided by ROTEM or
traditional laboratory testing. The subject will not be randomized in the study. In the case
of abnormal ROTEM parameters but no clinical evidence of microvascular bleeding as evaluated
by the cardiac surgeon, the subject will continue to be monitored carefully for bleeding for
the remainder of the procedure. If non-surgical bleeding is subsequently observed prior to
chest closure and the consensus is that fibrinogen is needed based on ROTEM results (FIBTEM
A10 less than or equal to 10 mm), the subject will be treated with their randomized study
product according to the algorithm. Following completion of the procedure, postoperative
coagulation management will be according to standard practice and guided by standard
laboratory testing, when possible. Unless persistent bleeding is noted, all subjects will
receive aspirin (300 mg per rectum) 6 hours postoperatively. Subjects with mechanical or
mitral tissue valves will be anticoagulated with warfarin (no heparin bridge) starting on
postoperative day two (POD#2). Any subjects experiencing significant arrhythmias (e.g. atrial
fibrillation in the perioperative setting) will also be anticoagulated with warfarin.
Pharmacologic deep vein thrombosis (DVT) prophylaxis will follow the usual standard of care.
Subjects enrolled, randomized, and transfused study product will be observed until hospital
discharge (total observation time). Research staff from the Department of Anesthesiology will
collect outcomes data, including transfused blood products, laboratory results, evidence of
perioperative thrombosis or infection, returns to the OR, length of stay, and mortality using
case report forms reports and enter all collected data into a secure REDCap database.

Inclusion Criteria:

1. All subjects age 18 and older who have given written informed consent

2. Undergoing cardiac surgery cardiopulmonary bypass (CBP) at Weill Cornell Medical
Center

Exclusion Criteria:

1. Subjects on anticoagulation medications including:

- Clopidogrel, ticagrelor, prasugrel with platelet function analyzer-100 assay
closure time (CT) prolonged greater than 15%

- Last doses of dabigatran, rivaroxaban, apixaban within 72 hours

- Warfarin with international normalized ratio (INR) greater than 1.5

2. Positive pregnancy test, pregnancy or lactation

3. Thrombocytopenia: platelet count less than 100,000 u/L

4. Emergency procedures

5. Proof or suspicion of a congenital or acquired coagulation disorder (e.g. von
Willebrand Factor or via severe liver disease)

6. Participation in another randomized clinical trial