- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05523297
Active-control Randomised Trial Comparing 4-factor Prothrombin Complex Concentrate With Frozen Plasma in Cardiac Surgery (FARES-2)
Prospective, Multicentre, Active-control Randomised Trial Comparing 4-factor Prothrombin Complex Concentrate With Frozen Plasma in Bleeding Adult Cardiac Surgical Patients
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Sigurd Knaub
- Phone Number: +41795330529
- Email: Sigurd.Knaub@Octapharma.com
Study Locations
-
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British Columbia
-
New Westminster, British Columbia, Canada, V3L 3W7
- Recruiting
- Royal Columbian Hospital
-
Vancouver, British Columbia, Canada, V5Z 1M9
- Recruiting
- University of British Columbia and Vancouver Coastal Health Authority
-
-
Ontario
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Hamilton, Ontario, Canada, L8L 8E7
- Recruiting
- Hamilton Health Sciences Corporation
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Kingston, Ontario, Canada, K7L 2V7
- Recruiting
- Kingston General Hospital
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London, Ontario, Canada, N6A 5A5
- Recruiting
- London Health Sciences
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Ottawa, Ontario, Canada, K1Y 4W7
- Recruiting
- University of Ottawa Heart Institute
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Toronto, Ontario, Canada, M5B 1W8
- Recruiting
- St. Michael's Hospital
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Toronto, Ontario, Canada, M5G 2C4
- Recruiting
- Toronto General Hospital
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Toronto, Ontario, Canada, M4N 3M5
- Recruiting
- Sunnybrook Hospital
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Quebec
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Montréal, Quebec, Canada, H1T 1C8
- Recruiting
- Montreal Heart Institute
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Québec, Quebec, Canada, G1V 4G5
- Recruiting
- Quebec Laval
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-
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North Carolina
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Durham, North Carolina, United States, 27710
- Recruiting
- Duke University Health System
-
-
Oklahoma
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Oklahoma City, Oklahoma, United States, 73104
- Recruiting
- University of Oklahoma Health Sciences Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Octaplex
Each participant to receive up to 2 Octaplex infusion intravenously within first 24 hours.
Exceeding 24 hours frozen plasma will be administered
|
Prothrombin complex concentrate
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Active Comparator: Frozen plasma
Each participant will be administered FP according to the local standard
|
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
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of patients requiring additional hemostatic intervention
Time Frame: 60 minutes to 24 hours after first dose of IMP
|
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.
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60 minutes to 24 hours after first dose of IMP
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of patients requiring additional hemostatic intervention based on hemoglobin level
Time Frame: 60 minutes to 24 hours after first dose of IMP
|
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.
|
60 minutes to 24 hours after first dose of IMP
|
Compare the amount of chest tube drainage between the Octaplex and FP groups.
Time Frame: 12 and 24 hours after chest closure
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12 and 24 hours after chest closure
|
|
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
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24 hours after surgery start, after the end of CPB and after IMP initiation
|
|
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
|
24 hours after the end of CPB and after IMP initiation
|
|
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
|
24 hours after the end of CPB and after IMP initiation
|
|
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
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24 hours and 7 days after the end of CPB and after IMP initiation
|
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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
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24 hours and 7 days after start of surgery, and after the end of CPB and after IMP initiation
|
|
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
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24 hours and 7 days after start of surgery and after the end of CPB and after IMP initiation
|
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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
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24 hours and 7 days after the start of surgery, after the end of CPB and after IMP initiation
|
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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
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24 hours after start of surgery, after the end of CPB and after IMP initiation
|
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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
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24 hours after start of surgery, after the end of CPB and after IMP initiation
|
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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
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24 hours after start of surgery, after the end of CPB and after IMP initiation
|
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Compare the effect of Octaplex versus FP administration on the change in international normalised ratio (INR) before and after therapy administration.
Time Frame: Within 30 minutes before to within 60 minutes after the initiation of IMP administration.
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INR reduction will be considered successful if the magnitude of the reduction is >1.0 or the post-treatment level drops below 1.5
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Within 30 minutes before to within 60 minutes after the initiation of IMP administration.
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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
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Within 75 minutes before to within 75 minutes after the initiation of IMP administration
|
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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
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Within 75 minutes before to within 75 minutes after the initiation of IMP administration
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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
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Within 75 minutes before to within 75 minutes after the initiation of IMP administration
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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
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Within 75 minutes before to within 75 minutes after the initiation of IMP administration
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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
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Within 75 minutes before to within 75 minutes after the initiation of IMP administration
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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
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Within 75 minutes before to within 75 minutes after the initiation of IMP administration
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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
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Within 75 minutes before to within 75 minutes after the initiation of IMP administration
|
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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
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From start of IMP administration up to 30 days post-operatively
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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
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From start of IMP administration up to 30 days post-operatively
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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
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From start of IMP administration up to 30 days post-operatively
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Comparison of the duration of hospitalization between Octaplex and FP groups
Time Frame: From start of IMP administration up to 30 days post-operatively
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From start of IMP administration up to 30 days post-operatively
|
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Comparison of the incidence of death between Octaplex and FP groups
Time Frame: From start of IMP administration up to 30 days post-operatively
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From start of IMP administration up to 30 days post-operatively
|
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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
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From start of IMP administration up to 30 days post-operatively
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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)
|
From initiation of IMP to arrival at ICU room (within 24 hours)
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- LEX-211
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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