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Factor Replacement in Surgery (FARES)

Primary Purpose

Bleeding in Cardiac Surgery

Status
Unknown status
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Prothrombin Complex Concentrate
Frozen Plasma
Sponsored by
University Health Network, Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Bleeding in Cardiac Surgery focused on measuring Frozen Plasma (FP), Prothrombin Complex Concentrate (PCC), Octaplex, Coagulation Factor Replacement, Transfusion, Bleeding Cardiac Surgical Patients, Pilot, Phase 2

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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:

  1. Management of bleeding, or

  2. Anticipated bleeding in a patient who has

    1. been on-pump for >2 hours, or
    2. 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.

Exclusion Criteria:

Patients who meet any of the following criteria are not eligible for the study:

  1. Undergoing heart transplantation, insertion or removal of ventricular assist devices (not including intra-aortic balloon pump [IABP]), or repair of thoracoabdominal aneurysm
  2. 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)
  3. History of heparin induced thrombocytopenia
  4. Last preoperative INR >1.5 and patient on warfarin
  5. Taken dabigatran, rivaroxaban, apixaban, or edoxaban within 48 hours of start of surgery
  6. Administered PCC or FP within 48 hours before start of surgery
  7. History of severe allergic reaction to PCC or FP
  8. Refusal of allogeneic blood products due to religious or other reasons
  9. Known pregnancy

Sites / Locations

  • Sunnybrook Health Science Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Prothrombin Complex Concentrate

Frozen Plasma

Arm Description

Outcomes

Primary Outcome Measures

Treatment response
Administration of hemostatic agents including a second dose of IMP, platelet transfusion, or surgical re-exploration
Amount of allogeneic blood products
Number of patients who do not receive any RBC transfusions or any allogeneic blood transfusions

Secondary Outcome Measures

Full Information

First Posted
September 25, 2019
Last Updated
November 2, 2020
Sponsor
University Health Network, Toronto
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1. Study Identification

Unique Protocol Identification Number
NCT04114643
Brief Title
Factor Replacement in Surgery
Acronym
FARES
Official Title
Prothrombin Complex Concentrate Versus Frozen Plasma in Bleeding Adult Cardiac Surgical Patients: A Multicentre, Randomized, Active-control, Pragmatic, Phase 2 Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Unknown status
Study Start Date
September 24, 2019 (Actual)
Primary Completion Date
July 21, 2020 (Actual)
Study Completion Date
December 31, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bleeding in Cardiac Surgery
Keywords
Frozen Plasma (FP), Prothrombin Complex Concentrate (PCC), Octaplex, Coagulation Factor Replacement, Transfusion, Bleeding Cardiac Surgical Patients, Pilot, Phase 2

7. Study Design

Primary Purpose
Other
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
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.
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
103 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Prothrombin Complex Concentrate
Arm Type
Active Comparator
Arm Title
Frozen Plasma
Arm Type
Active Comparator
Intervention Type
Biological
Intervention Name(s)
Prothrombin Complex Concentrate
Other Intervention Name(s)
Octaplex
Intervention Description
Octaplex will be administered when the blood bank receives an order for coagulation factor replacement
Intervention Type
Biological
Intervention Name(s)
Frozen Plasma
Other Intervention Name(s)
Fresh Frozen Plasma
Intervention Description
Frozen Plasma will be administered when the blood bank receives an order for coagulation factor replacement
Primary Outcome Measure Information:
Title
Treatment response
Description
Administration of hemostatic agents including a second dose of IMP, platelet transfusion, or surgical re-exploration
Time Frame
At 4 and 24 hours
Title
Amount of allogeneic blood products
Time Frame
24 hours after the start of surgery
Title
Number of patients who do not receive any RBC transfusions or any allogeneic blood transfusions
Time Frame
first 24 hours after the start of surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Keyvan Karkouti, MD
Organizational Affiliation
University Health Network, Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sunnybrook Health Science Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33792729
Citation
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.
Results Reference
derived

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Factor Replacement in Surgery

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