Transfusion of Pathogen Reduced Cryoprecipitated Fibrinogen to Expedite Product Availability in Perioperative Bleeding

Bleeding Clinical Trial

Official title:

Pilot Clinical Trial of Transfusion of Pathogen Reduced Cryoprecipitated Fibrinogen (INTERCEPT Fibrinogen Complex) in Patients With Bleeding to Expedite Product Availability and Improve Outcomes in Perioperative Bleeding

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05711524
• Other study ID #: 22-04024649
• Status: Recruiting
• Phase: Phase 4
• Start date: April 1, 2023
• Est. completion date: March 2025

Study information

• Verified date: September 2023
• Source: Weill Medical College of Cornell University
• Contact: Melissa Cushing
• Phone: 212-746-3527
• Email: mec2013[@]med.cornell.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this quality improvement study is to compare pathogen-reduced cryoprecipitate with traditional cryoprecipitate in liver transplant and cardiovascular patients. The investigators hypothesize that by having immediate access to a readily available thawed blood product that replaces fibrinogen (the main substrate of a blood clot), early bleeding can be treated before it escalates into uncontrolled hemorrhage, and therefore additional blood products, like platelets, plasma and red blood cells can be avoided.

Participants will be given one of the two FDA-approved blood products.

Description:

Immediately replacing fibrinogen in perioperative bleeding patients with acquired fibrinogen deficiency improves outcomes. The product that is primarily used for fibrinogen replacement in the US, cryoprecipitate (cryo), must be stored frozen and expires six hours after thawing, resulting in a delay in transfusion of approximately 50 minutes from the time it is ordered, as well as unnecessary transfusion of more readily available but not indicated blood components that are transfused while the patients waits for cryo . A modified version of the product, pathogen reduced (PR) cryo, is now FDA approved and can be thawed and stored for 5 days, allowing the product to be available immediately when needed. In this quality improvement study, the investigators will compare the effect that readily available, pre-thawed PR cryo has on transfusion practice in cardiovascular and liver transplant patients who receive PR cryo versus those who receive traditional cryo by randomizing cryo transfusions in the blood bank by month to all cryo or all PR cryo. All clinical decisions, including the need for cryo, and laboratory testing will occur per standard of care.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 302
• Est. completion date: March 2025
• Est. primary completion date: March 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adult patients undergoing cardiovascular surgery or liver transplant who receive cryo during surgery during the two year study period.

2. Cardiovascular surgery includes the following procedures:

1. coronary artery bypass grafting

2. valve repair or replacement

3. open thoracic aortic and thoracoabdominal aortic surgery

4. atrial or ventricular septal defects

5. ventricular assist device implantation or revision

6. or any combination of the above.

Exclusion Criteria:

1. Patients who do not receive any cryo product in the OR

2. Patients who are not cardiovascular surgery or liver transplant patients

3. Cardiac transplantation surgery

4. Patients who receive a product in error within either the cryo time period or the PR cryo time period. For example, PR cryo during a cryo month or cryo during a PR cryo time month.

5. Patients who receive less than 1 pool (5 units) of cryo

6. Pediatric patients (less than 18 years of age).

7. Patients who received both PR cryo and traditional cryo

8. Pregnant women

Related Conditions & MeSH terms

• Bleeding
• Hemorrhage
• Hypofibrinogenemia

Intervention

Biological:
• Traditional Cryoprecipitate
This is the cryoprecipitate already currently being given to patients with a cryo order.
• Pathogen-Reduced Cryoprecipitate
This is the pathogen-reduced cryoprecipitate that is intended to be compared to the standard cryoprecipitate.

Locations

Country	Name	City	State
United States	New York-Presbyterian Hospital/Weill Cornell Medical Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	Cerus Corporation

Country where clinical trial is conducted

United States, 

References & Publications (9)

Arnup SJ, Forbes AB, Kahan BC, Morgan KE, McKenzie JE. Appropriate statistical methods were infrequently used in cluster-randomized crossover trials. J Clin Epidemiol. 2016 Jun;74:40-50. doi: 10.1016/j.jclinepi.2015.11.013. Epub 2015 Nov 26. — View Citation

Bulkley GB, Wheaton LG, Strandberg JD, Zuidema GD. Assessment of small intestinal recovery from ischemic injury after segmental, arterial, venous, and arteriovenous occlusion. Surg Forum. 1979;30:210-3. No abstract available. — View Citation

Cushing MM, Fitzgerald MM, Harris RM, Asmis LM, Haas T. Influence of cryoprecipitate, Factor XIII, and fibrinogen concentrate on hyperfibrinolysis. Transfusion. 2017 Oct;57(10):2502-2510. doi: 10.1111/trf.14259. Epub 2017 Jul 21. — View Citation

Cushing MM, Haas T, Karkouti K, Callum J. Which is the preferred blood product for fibrinogen replacement in the bleeding patient with acquired hypofibrinogenemia-cryoprecipitate or fibrinogen concentrate? Transfusion. 2020 Jun;60 Suppl 3:S17-S23. doi: 10.1111/trf.15614. Epub 2020 Jun 1. — View Citation

Fenderson JL, Meledeo MA, Rendo MJ, Peltier GC, McIntosh CS, Davis KW, Corley JB, Cap AP. Hemostatic characteristics of thawed, pooled cryoprecipitate stored for 35 days at refrigerated and room temperatures. Transfusion. 2019 Apr;59(S2):1560-1567. doi: 10.1111/trf.15180. — View Citation

Hsien S, Dayton JD, Chen D, Stock A, Bacha E, Cushing MM, Nellis ME. Hemostatic efficacy of pathogen-reduced platelets in children undergoing cardiopulmonary bypass. Transfusion. 2022 Feb;62(2):298-305. doi: 10.1111/trf.16768. Epub 2021 Dec 13. — View Citation

Lokhandwala PM, O'Neal A, Patel EU, Brunker PAR, Gehrie EA, Zheng G, Kickler TS, Ness PM, Tobian AAR. Hemostatic profile and safety of pooled cryoprecipitate up to 120 hours after thawing. Transfusion. 2018 May;58(5):1126-1131. doi: 10.1111/trf.14550. Epub 2018 Feb 25. — View Citation

Saland LC. Effects of reserpine administration on the fine structure of the rat pars intermedia. Cell Tissue Res. 1978 Nov 9;194(1):115-23. doi: 10.1007/BF00209237. — View Citation

Thomson C, Sobieraj-Teague M, Scott D, Duncan E, Abraham S, Roxby D. Extending the post-thaw viability of cryoprecipitate. Transfusion. 2021 May;61(5):1578-1585. doi: 10.1111/trf.16366. Epub 2021 Mar 17. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total number of RBCs used over admission		Within the first 30 days after surgery.
Primary	Total number of platelets used over admission		Within the first 30 days after surgery.
Primary	Total number of plasma used over admission		Within the first 30 days after surgery.
Secondary	Number of cryo or fibrinogen concentrate products used perioperatively		3 days post procedure
Secondary	Number of RBCs used perioperatively		3 days post procedure
Secondary	Number of plasma used perioperatively		3 days post procedure
Secondary	Number of platelets used perioperatively		3 days post procedure
Secondary	Time from OR start time to start of cryo transfusion		procedure (Time from OR start time to start of cryo transfusion)
Secondary	Time from cryo order to start of transfusion		procedure (Time from cryo order to start of transfusion)
Secondary	Number of cryo units wasted by blood bank		Daily, up to approximately 24 months
Secondary	Pre transfusion FIBTEM amplitude at 10mins		Within 10 minutes to one hour after the end of the first cryo transfusion.
Secondary	Post transfusion FIBTEM amplitude at 10mins		Within 10 minutes to one hour after the end of the first cryo transfusion.
Secondary	Maximum clot firmness at 10mins		Within 10 minutes to one hour after the end of the first cryo transfusion.
Secondary	Fibrinogen level at 10mins		Within 10 minutes to one hour after the end of the first cryo transfusion.
Secondary	Highest fibrinogen level within 24 hours		Within 24 hours after surgery
Secondary	Lowest fibrinogen level within 24 hours		Within 24 hours after surgery
Secondary	Cumulative volume in drains after surgery (e.g., chest tube for CV surgery) at the time of removal		Up to approximately 3 days
Secondary	Volume in drains (e.g. chest tube for CV surgery)		At 24 hours after surgery
Secondary	Time from end of bypass pump for CV surgery		Until end of surgery
Secondary	Length of stay in OR		During hospitalization, approximately 5 days to 30 days
Secondary	Length of stay in ICU		During hospitalization, approximately 5 days to 30 days
Secondary	Length of stay in hospital		During hospitalization, approximately 5 days to 30 days
Secondary	Need for ventilator		During hospitalization, approximately 5 days to 30 days
Secondary	Time on ventilator		During hospitalization, approximately 5 days to 30 days
Secondary	Overall cost of cryo vs PR cryo, when factoring wastage		Daily, approximately 24 months
Secondary	Number of adverse events: fevers	All fevers that occur during the time frame	Within 5 days of surgery start time
Secondary	Number of adverse events: infections	All infections that occur during the time frame	Within 5 days of surgery start time
Secondary	Number of adverse events: transfusion reactions	All transfusion reactions that occur during the time frame	Within 5 days of surgery start time
Secondary	Fibrinogen level		Most proximal to end of procedure