Clinical trial NCT02540434: Trial of RiaSTAP Versus Cryoprecipitate to Lower Operative Transfusions
Official title: Trial of RiaSTAP Versus Cryoprecipitate to Lower Operative Transfusions (TOP-CLOT)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Coagulopathy
Keywords: Hypofibrinogenemia
ROTEM
Cardiac Surgery
Concentrated Fibrinogen
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
First posted: 2015-09-04
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study aligns with the strategic plan of New York-Presbyterian Hospital (NYPH) to reduce allogeneic blood product use and decrease unnecessary laboratory costs. One of the NYPH Quality and Patient Safety Goals for 2013 was to improve the appropriate use of transfusion guidelines and reduce unnecessary red blood cell (RBC) transfusions. Further, this study will help to answer whether RiaSTAP is a more effective product to treat bleeding than cryoprecipitate. In addition, this trial will provide investigators with preliminary data to apply for future federal funding opportunities, such as the National Heart Lung and Blood Institute sponsored R21 grant (PAR-13-025) that encourages research grant applications from investigators who propose to study research topics in blood banking and transfusion medicine aimed at improving the safety and availability of the blood supply and the practice of transfusion medicine. The investigators anticipate future follow-on studies further investigating fibrinogen concentrate and other similar therapeutics in other perioperative populations, such as in postpartum hemorrhage or surgical ICU settings. Finally, this study involves the use of a safer therapeutic, fibrinogen concentrate, to improve patient care and patient safety. This product does not require the time-intensive process of thawing; therefore, delays in patient care can be avoided by having the product readily available in the OR.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Intraoperative Blood Transfusion Total
timeFrame: Procedure length, the average for participants is approximately 6 hours
Secondary outcomes:
measure: 24-hour Blood Transfusion Total
timeFrame: 24 hours
measure: Fibrinogen Repletion
timeFrame: Procedure length, the average for participants is approximately 6 hours
measure: Incidence of Zero Transfusions
timeFrame: 24 hours
measure: Correction of Microvascular Bleeding
timeFrame: ~30 min intraoperatively
measure: CTICU Length of Stay
timeFrame: Length of Hospital Stay, the average for participants is approximately 7 days
measure: Hospital Length of Stay
timeFrame: Length of Hospital Stay, the average for participants is approximately 7 days
measure: Thrombosis and Transfusion Reactions
timeFrame: Length of Hospital Stay, the average for participants is approximately 7 days
measure: Infection and Respiratory Failure
timeFrame: Length of Hospital Stay, the average for participants is approximately 7 days
measure: Blood Loss
timeFrame: Length of Hospital Stay, the average for participants is approximately 7 days,
measure: Incidence of Re-exploration
timeFrame: Length of Hospital Stay, the average for participants is approximately 7 days
measure: Mortality Rate
timeFrame: Length of Hospital Stay, the average for participants is approximately 7 days
measure: Correlation of Laboratory and ROTEM Data
timeFrame: Procedure length, the average for participants is approximately 6 hours
measure: Time to Product Administration
timeFrame: Procedure length, the average for participants is approximately 6 hours
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Nikolaos J Skubas, M.D.
role: PRINCIPAL_INVESTIGATOR
References: