Back to resultsActive-control Randomised Trial Comparing 4-factor Prothrombin Complex Concentrate With Frozen Plasma in Cardiac Surgery (FARES-2)
Primary Purpose
Bleeding Cardiac Surgery Patients
Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Octaplex
Frozen Plasma Product, Human
Sponsored by
About this trial
This is an interventional treatment trial for Bleeding Cardiac Surgery Patients
Eligibility Criteria
Inclusion Criteria:
- Adult (≥18 years old) patients undergoing any index cardiac surgery employing CPB
Coagulation factor replacement with PCC or FP ordered in the operating room for:
- Management of bleeding, or
- Anticipated bleeding in a patient who has been on-pump for >2 hours or has undergone a complex procedure (e.g., aortocoronary bypass [ACB] plus aortic valve replacement)
- Coagulation factor deficiency, either known to exist (e.g., as indicated by elevated EXTEM clotting time [CT] or INR) or suspected based on the clinical situation
- Patients who have given written informed consent. In United States patients will provide informed consent prior to surgery. In Canada, informed consent will be obtained after surgery, in accordance with Article 3.7A of the 2018 Tri- Council Policy Statement on the Ethical Conduct for Research Involving Humans.
Exclusion Criteria:
- 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 surgery with high probability of death within 24 hours of surgery (e.g., acute aortic dissection, cardiac arrest within 24 hours before surgery)
- Severe right heart failure (clinical diagnosis ± echocardiography)
- Known contraindications to heparin
- PCC required for reversal of warfarin or direct oral anticoagulant (DOAC; dabigatran, rivaroxaban, apixaban or edoxaban) within 3 days prior to or during surgery
- Known thromboembolic event (TEE) within 3 months prior to surgery
- History of severe allergic reactions to PCC or FP
- Individuals who have immunoglobulin A (IgA) deficiency with known antibodies against IgA
- Refusal of allogeneic blood products
- Known pregnancy
- Currently enrolled in other interventional clinical trials
Sites / Locations
- Duke University Health SystemRecruiting
- University of Oklahoma Health Sciences CenterRecruiting
- Royal Columbian HospitalRecruiting
- University of British Columbia and Vancouver Coastal Health AuthorityRecruiting
- Hamilton Health Sciences CorporationRecruiting
- Kingston General HospitalRecruiting
- London Health SciencesRecruiting
- University of Ottawa Heart InstituteRecruiting
- Sunnybrook HospitalRecruiting
- St. Michael's Hospital
- Toronto General HospitalRecruiting
- Montreal Heart Institute
- Quebec LavalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Octaplex
Frozen plasma
Arm Description
Each participant to receive up to 2 Octaplex infusion intravenously within first 24 hours. Exceeding 24 hours frozen plasma will be administered
Each participant will be administered FP according to the local standard
Outcomes
Primary Outcome Measures
Number of patients requiring additional hemostatic intervention
Defined as 'effective' if no additional hemostatic intervention, such as administration of any systemic hemostatic agents (including platelets, cryoprecipitate, fibrinogen concentrate, activated recombinant factor VII, other coagulation factor products or a second dose of IMP) or any hemostatic interventions (including surgical re-opening for bleeding) is required from 60 minutes to 24 hours after initiation of the first dose of IMP.
Secondary Outcome Measures
Number of patients requiring additional hemostatic intervention based on hemoglobin level
Defined as 'positive' if no additional hemostatic intervention is required and hemoglobin levels decrease by <30% (after accounting for red cell transfusions) from 60 minutes to 24 hours after initiation of the first dose of IMP.
Compare the amount of chest tube drainage between the Octaplex and FP groups.
Compare the incidence of severe to massive bleeding between the Octaplex and FP groups using a modification of the universal definition of perioperative bleeding (UDPB).
Compare efficacy in terms of the mean number of total allogeneic blood components (IMP and non-IMP) transfused between the Octaplex and FP groups.
Compare efficacy in terms of the mean number of total non-IMP allogeneic blood components transfused between the Octaplex and FP groups.
Compare efficacy in terms of the mean number of total non-IMP allogeneic blood components transfused between the Octaplex and FP groups.
Compare mean number of individual allogeneic blood components transfused between the Octaplex and FP groups.
Compare efficacy in terms of the incidence of transfusion of individual allogeneic blood components transfused between the Octaplex and FP groups.
Compare incidence of administration of non-IMP coagulation factor products between Octaplex and FP groups
Compare incidence of intracerebral hemorrhage between the Octaplex and FP groups
Compare incidence of gastrointestinal hemorrhage between Octaplex and FP groups
Compare incidence of surgical re-exploration between Octaplex and FP groups
Compare the effect of Octaplex versus FP administration on the change in international normalised ratio (INR) before and after therapy administration.
INR reduction will be considered successful if the magnitude of the reduction is >1.0 or the post-treatment level drops below 1.5
Compare the effect of Octaplex versus FP administration on Prothrombin Time (PT)
Compare the effect of Octaplex versus FP administration on aPTT
Compare the effect of Octaplex versus FP administration on fibrinogen activity
Compare the effect of Octaplex versus FP administration on ROTEM EXTEM CT
Compare the effect of Octaplex versus FP administration on ROTEM EXTEM MCT
Compare the effect of Octaplex versus FP administration on ROTEM FIBTEM MCF
Compare the effect of Octaplex versus FP administration on platelets
Compare total time elapsed from initiation of the first dose of IMP to arrival at the ICU room between the Octaplex and FP groups.
Comparison of incidence of serious treatment-emergent adverse events between Octaplex and FP groups
Comparison of the duration of mechanical ventilation between Octaplex and FP groups
Comparison of the duration of ICU stay between Octaplex and FP groups
Comparison of the duration of hospitalization between Octaplex and FP groups
Comparison of the incidence of death between Octaplex and FP groups
Comparison of the number of days alive and out of hospital between Octaplex and FP groups
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05523297
Brief Title
Active-control Randomised Trial Comparing 4-factor Prothrombin Complex Concentrate With Frozen Plasma in Cardiac Surgery
Acronym
FARES-2
Official Title
Prospective, Multicentre, Active-control Randomised Trial Comparing 4-factor Prothrombin Complex Concentrate With Frozen Plasma in Bleeding Adult Cardiac Surgical Patients
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 10, 2022 (Actual)
Primary Completion Date
October 2024 (Anticipated)
Study Completion Date
October 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Octapharma
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a multicentre, active-control randomized, prospective, Phase 3 study in adult cardiac surgery patients. Approximately 500 patients will be randomized at approximately 12 hospitals.
Detailed Description
Patients will be randomized to receive either 4-factor PCC (Octaplex) or frozen plasma (FP).
The study will compare the hemostatic treatment response to Octaplex versus FP, defined as effective if no additional systemic or surgical hemostatic intervention is required from 60 minutes to 24 hours after initiation of the first treatment dose.
The study will include adult (≥18 years old) patients who undergo cardiac surgery with cardiopulmonary bypass (CPB) and require coagulation factor replacement due to bleeding post-CPB and after adequate reversal of heparin with protamine (as assessed by the surgical staff based on clinical and laboratory criteria) during surgery, and who have a known (e.g., as indicated by INR) or suspected coagulation factor deficiency.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bleeding Cardiac Surgery Patients
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Masking Description
Given the physical differences in the products and the emergency nature of the intervention, attending clinicians present during the infusion of the blood products/components will not be blinded to the treatment. To minimize bias, treating clinicians will be blinded to group assignments until immediately prior to IMP infusion.
Allocation
Randomized
Enrollment
500 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Octaplex
Arm Type
Experimental
Arm Description
Each participant to receive up to 2 Octaplex infusion intravenously within first 24 hours. Exceeding 24 hours frozen plasma will be administered
Arm Title
Frozen plasma
Arm Type
Active Comparator
Arm Description
Each participant will be administered FP according to the local standard
Intervention Type
Drug
Intervention Name(s)
Octaplex
Intervention Description
Prothrombin complex concentrate
Intervention Type
Drug
Intervention Name(s)
Frozen Plasma Product, Human
Intervention Description
If additional treatment is required after the maximum dose of IMP is administered or the treatment period has elapsed, patients in both groups will receive frozen plasma
Primary Outcome Measure Information:
Title
Number of patients requiring additional hemostatic intervention
Description
Defined as 'effective' if no additional hemostatic intervention, such as administration of any systemic hemostatic agents (including platelets, cryoprecipitate, fibrinogen concentrate, activated recombinant factor VII, other coagulation factor products or a second dose of IMP) or any hemostatic interventions (including surgical re-opening for bleeding) is required from 60 minutes to 24 hours after initiation of the first dose of IMP.
Time Frame
60 minutes to 24 hours after first dose of IMP
Secondary Outcome Measure Information:
Title
Number of patients requiring additional hemostatic intervention based on hemoglobin level
Description
Defined as 'positive' if no additional hemostatic intervention is required and hemoglobin levels decrease by <30% (after accounting for red cell transfusions) from 60 minutes to 24 hours after initiation of the first dose of IMP.
Time Frame
60 minutes to 24 hours after first dose of IMP
Title
Compare the amount of chest tube drainage between the Octaplex and FP groups.
Time Frame
12 and 24 hours after chest closure
Title
Compare the incidence of severe to massive bleeding between the Octaplex and FP groups using a modification of the universal definition of perioperative bleeding (UDPB).
Time Frame
24 hours after surgery start, after the end of CPB and after IMP initiation
Title
Compare efficacy in terms of the mean number of total allogeneic blood components (IMP and non-IMP) transfused between the Octaplex and FP groups.
Time Frame
24 hours after the end of CPB and after IMP initiation
Title
Compare efficacy in terms of the mean number of total non-IMP allogeneic blood components transfused between the Octaplex and FP groups.
Time Frame
24 hours after the end of CPB and after IMP initiation
Title
Compare efficacy in terms of the mean number of total non-IMP allogeneic blood components transfused between the Octaplex and FP groups.
Time Frame
24 hours and 7 days after the end of CPB and after IMP initiation
Title
Compare mean number of individual allogeneic blood components transfused between the Octaplex and FP groups.
Time Frame
24 hours and 7 days after start of surgery, and after the end of CPB and after IMP initiation
Title
Compare efficacy in terms of the incidence of transfusion of individual allogeneic blood components transfused between the Octaplex and FP groups.
Time Frame
24 hours and 7 days after start of surgery and after the end of CPB and after IMP initiation
Title
Compare incidence of administration of non-IMP coagulation factor products between Octaplex and FP groups
Time Frame
24 hours and 7 days after the start of surgery, after the end of CPB and after IMP initiation
Title
Compare incidence of intracerebral hemorrhage between the Octaplex and FP groups
Time Frame
24 hours after start of surgery, after the end of CPB and after IMP initiation
Title
Compare incidence of gastrointestinal hemorrhage between Octaplex and FP groups
Time Frame
24 hours after start of surgery, after the end of CPB and after IMP initiation
Title
Compare incidence of surgical re-exploration between Octaplex and FP groups
Time Frame
24 hours after start of surgery, after the end of CPB and after IMP initiation
Title
Compare the effect of Octaplex versus FP administration on the change in international normalised ratio (INR) before and after therapy administration.
Description
INR reduction will be considered successful if the magnitude of the reduction is >1.0 or the post-treatment level drops below 1.5
Time Frame
Within 30 minutes before to within 60 minutes after the initiation of IMP administration.
Title
Compare the effect of Octaplex versus FP administration on Prothrombin Time (PT)
Time Frame
Within 75 minutes before to within 75 minutes after the initiation of IMP administration
Title
Compare the effect of Octaplex versus FP administration on aPTT
Time Frame
Within 75 minutes before to within 75 minutes after the initiation of IMP administration
Title
Compare the effect of Octaplex versus FP administration on fibrinogen activity
Time Frame
Within 75 minutes before to within 75 minutes after the initiation of IMP administration
Title
Compare the effect of Octaplex versus FP administration on ROTEM EXTEM CT
Time Frame
Within 75 minutes before to within 75 minutes after the initiation of IMP administration
Title
Compare the effect of Octaplex versus FP administration on ROTEM EXTEM MCT
Time Frame
Within 75 minutes before to within 75 minutes after the initiation of IMP administration
Title
Compare the effect of Octaplex versus FP administration on ROTEM FIBTEM MCF
Time Frame
Within 75 minutes before to within 75 minutes after the initiation of IMP administration
Title
Compare the effect of Octaplex versus FP administration on platelets
Time Frame
Within 75 minutes before to within 75 minutes after the initiation of IMP administration
Title
Compare total time elapsed from initiation of the first dose of IMP to arrival at the ICU room between the Octaplex and FP groups.
Time Frame
From initiation of IMP to arrival at ICU room (within 24 hours)
Title
Comparison of incidence of serious treatment-emergent adverse events between Octaplex and FP groups
Time Frame
From start of IMP administration up to 30 days post-operatively
Title
Comparison of the duration of mechanical ventilation between Octaplex and FP groups
Time Frame
From start of IMP administration up to 30 days post-operatively
Title
Comparison of the duration of ICU stay between Octaplex and FP groups
Time Frame
From start of IMP administration up to 30 days post-operatively
Title
Comparison of the duration of hospitalization between Octaplex and FP groups
Time Frame
From start of IMP administration up to 30 days post-operatively
Title
Comparison of the incidence of death between Octaplex and FP groups
Time Frame
From start of IMP administration up to 30 days post-operatively
Title
Comparison of the number of days alive and out of hospital between Octaplex and FP groups
Time Frame
From start of IMP administration up to 30 days post-operatively
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult (≥18 years old) patients undergoing any index cardiac surgery employing CPB
Coagulation factor replacement with PCC or FP ordered in the operating room for:
Management of bleeding, or
Anticipated bleeding in a patient who has been on-pump for >2 hours or has undergone a complex procedure (e.g., aortocoronary bypass [ACB] plus aortic valve replacement)
Coagulation factor deficiency, either known to exist (e.g., as indicated by elevated EXTEM clotting time [CT] or INR) or suspected based on the clinical situation
Patients who have given written informed consent. In United States patients will provide informed consent prior to surgery. In Canada, informed consent will be obtained after surgery, in accordance with Article 3.7A of the 2018 Tri- Council Policy Statement on the Ethical Conduct for Research Involving Humans.
Exclusion Criteria:
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 surgery with high probability of death within 24 hours of surgery (e.g., acute aortic dissection, cardiac arrest within 24 hours before surgery)
Severe right heart failure (clinical diagnosis ± echocardiography)
Known contraindications to heparin
PCC required for reversal of warfarin or direct oral anticoagulant (DOAC; dabigatran, rivaroxaban, apixaban or edoxaban) within 3 days prior to or during surgery
Known thromboembolic event (TEE) within 3 months prior to surgery
History of severe allergic reactions to PCC or FP
Individuals who have immunoglobulin A (IgA) deficiency with known antibodies against IgA
Refusal of allogeneic blood products
Known pregnancy
Currently enrolled in other interventional clinical trials
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sigurd Knaub
Phone
+41795330529
Email
Sigurd.Knaub@Octapharma.com
Facility Information:
Facility Name
Duke University Health System
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Individual Site Status
Recruiting
Facility Name
Royal Columbian Hospital
City
New Westminster
State/Province
British Columbia
ZIP/Postal Code
V3L 3W7
Country
Canada
Individual Site Status
Recruiting
Facility Name
University of British Columbia and Vancouver Coastal Health Authority
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 1M9
Country
Canada
Individual Site Status
Recruiting
Facility Name
Hamilton Health Sciences Corporation
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8L 8E7
Country
Canada
Individual Site Status
Recruiting
Facility Name
Kingston General Hospital
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 2V7
Country
Canada
Individual Site Status
Recruiting
Facility Name
London Health Sciences
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5A5
Country
Canada
Individual Site Status
Recruiting
Facility Name
University of Ottawa Heart Institute
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4W7
Country
Canada
Individual Site Status
Recruiting
Facility Name
Sunnybrook Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Individual Site Status
Recruiting
Facility Name
St. Michael's Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B 1W8
Country
Canada
Individual Site Status
Not yet recruiting
Facility Name
Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
Individual Site Status
Recruiting
Facility Name
Montreal Heart Institute
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H1T 1C8
Country
Canada
Individual Site Status
Not yet recruiting
Facility Name
Quebec Laval
City
Québec
State/Province
Quebec
ZIP/Postal Code
G1V 4G5
Country
Canada
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Active-control Randomised Trial Comparing 4-factor Prothrombin Complex Concentrate With Frozen Plasma in Cardiac Surgery
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