Factor Replacement in Surgery

Study Overview
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Brief Summary
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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.

Official Title
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Prothrombin Complex Concentrate Versus Frozen Plasma in Bleeding Adult Cardiac Surgical Patients: A Multicentre, Randomized, Active-control, Pragmatic, Phase 2 Pilot Study

Conditions
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Bleeding in Cardiac Surgery

Intervention / Treatment
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* Biological: Prothrombin Complex Concentrate
* Biological: Frozen Plasma


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Prothrombin Complex Concentrate<br> | Biological: Prothrombin Complex Concentrate<br>* Octaplex will be administered when the blood bank receives an order for coagulation factor replacement<br>* Other names: Octaplex;|
| Active Comparator: Frozen Plasma<br> | Biological: Frozen Plasma<br>* Frozen Plasma will be administered when the blood bank receives an order for coagulation factor replacement<br>* Other names: Fresh Frozen Plasma;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Frozen Plasma (FP), Prothrombin Complex Concentrate (PCC), Octaplex, Coagulation Factor Replacement, Transfusion, Bleeding Cardiac Surgical Patients, Pilot, Phase 2