Factor Replacement in Surgery

NCT04114643 | Unknown Phase 2 DMC

• 1 other identifier: 19-5393
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicentre, randomized, active-control, pragmatic, Phase 2 pilot study in adult cardiac surgery patients. Two Canadian hospitals will participate, and it is estimated that the study will take approximately 9 months to complete. Approximately 120 bleeding adult cardiac surgical patients who require coagulation factor replacement during cardiac surgery will be included. Patients will be randomized to receive either PCC or FP when the blood bank receives the first order for coagulation factor replacement and deems it to be in accordance with accepted clinical standards. Patients will be treated according to their assigned group on the first and second times when coagulation factor replacement is ordered during the treatment period (24 hours after randomization). For any additional doses (i.e., the third dose and thereafter), patients in both groups will receive FP (in 1U increments at the discretion of the ordering physician). No other aspects of care will be modified. This pilot study aims to select a clinically relevant primary efficacy endpoint for a confirmative Phase 3 study, which will subsequently aim to determine if PCC is non-inferior or superior to FP in terms of effica-cy and safety in bleeding cardiac surgical patients. In the pilot study, safety outcomes will be measured for the first 28 days, which is the duration of participation of each patient in the trial.

Conditions

Bleeding in Cardiac Surgery

Keywords

Frozen Plasma (FP); Prothrombin Complex Concentrate (PCC); Octaplex; Coagulation Factor Replacement; Transfusion; Bleeding Cardiac Surgical Patients; Pilot; Phase 2

Outcome Measures

Primary Outcomes (3)

• Treatment response

  Administration of hemostatic agents including a second dose of IMP, platelet transfusion, or surgical re-exploration

  At 4 and 24 hours

• Amount of allogeneic blood products

  24 hours after the start of surgery

• Number of patients who do not receive any RBC transfusions or any allogeneic blood transfusions

  first 24 hours after the start of surgery

Study Arms (2)

Prothrombin Complex Concentrate

ACTIVE COMPARATOR

Biological: Prothrombin Complex Concentrate

Frozen Plasma

ACTIVE COMPARATOR

Biological: Frozen Plasma

Interventions

Prothrombin Complex Concentrate BIOLOGICAL

Octaplex will be administered when the blood bank receives an order for coagulation factor replacement

Also known as: Octaplex

Prothrombin Complex Concentrate

Frozen Plasma BIOLOGICAL

Frozen Plasma will be administered when the blood bank receives an order for coagulation factor replacement

Also known as: Fresh Frozen Plasma

Frozen Plasma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients undergoing any index cardiac surgery with or without CPB in whom coagulation factor replacement with PCC or FP is ordered in the operating room for:
• Management of bleeding, or
• Anticipated bleeding in a patient who has
• been on-pump for \>2 hours, or
• undergone a complex procedure (e.g., ACB + AVR). Coagulation factor deficiency must either be known to exist (as indicated by elevated EXTEM clotting time \[CT\] or international normalized ratio \[INR\]), or be suspected based on the clinical situation.

You may not qualify if:

• Patients who meet any of the following criteria are not eligible for the study:
• Undergoing heart transplantation, insertion or removal of ventricular assist devices (not including intra-aortic balloon pump \[IABP\]), or repair of thoracoabdominal aneurysm
• Critical state immediately before emergency surgery with high probability of death within 24 hours of surgery (e.g., acute aortic dissection, cardiac arrest within 24 hours before start of surgery)
• History of heparin induced thrombocytopenia
• Last preoperative INR \>1.5 and patient on warfarin
• Taken dabigatran, rivaroxaban, apixaban, or edoxaban within 48 hours of start of surgery
• Administered PCC or FP within 48 hours before start of surgery
• History of severe allergic reaction to PCC or FP
• Refusal of allogeneic blood products due to religious or other reasons
• Known pregnancy

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Sunnybrook Health Science Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Related Publications (2)

• Hayes K, Fernando MC, Jordan V. Prothrombin complex concentrate in cardiac surgery for the treatment of coagulopathic bleeding. Cochrane Database Syst Rev. 2022 Nov 21;11(11):CD013551. doi: 10.1002/14651858.CD013551.pub2.

  PMID: 36408876 DERIVED

• Karkouti K, Bartoszko J, Grewal D, Bingley C, Armali C, Carroll J, Hucke HP, Kron A, McCluskey SA, Rao V, Callum J. Comparison of 4-Factor Prothrombin Complex Concentrate With Frozen Plasma for Management of Hemorrhage During and After Cardiac Surgery: A Randomized Pilot Trial. JAMA Netw Open. 2021 Apr 1;4(4):e213936. doi: 10.1001/jamanetworkopen.2021.3936.

  PMID: 33792729 DERIVED

MeSH Terms

Conditions

Hemophilia B

Interventions

Factor IX; prothrombin complex concentrates

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Intervention Hierarchy (Ancestors)

Enzyme Precursors; Enzymes and Coenzymes; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Study Officials

• Keyvan Karkouti, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will be randomized to receive either PCC or FP when the blood bank receives the first order for coagulation factor replacement and deems it to be in accordance with accepted clinical standards.

Study Record Dates

• First Submitted: September 25, 2019
• First Posted: October 3, 2019
• Study Start: September 24, 2019
• Primary Completion: July 21, 2020
• Study Completion: December 31, 2020
• Last Updated: November 3, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)