Clinical trial NCT05523297: Active-control Randomised Trial Comparing 4-factor Prothrombin Complex Concentrate With Frozen Plasma in Cardiac Surgery
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bleeding Cardiac Surgery Patients
Lead sponsor: Octapharma
Sponsor class: INDUSTRY
First posted: 2022-08-31
Enrollment: 419
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Adult (≥18 years old) patients undergoing any index cardiac surgery employing CPB
2. Coagulation factor replacement with PCC or FP ordered in the operating room for:

   1. Management of bleeding, or
   2. 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)
3. 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
4. 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:

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 surgery with high probability of death within 24 hours of surgery (e.g., acute aortic dissection, cardiac arrest within 24 hours before surgery)
3. Severe right heart failure (clinical diagnosis ± echocardiography)
4. Known contraindications to heparin
5. PCC required for reversal of warfarin or direct oral anticoagulant (DOAC; dabigatran, rivaroxaban, apixaban or edoxaban) within 3 days prior to or during surgery
6. Known thromboembolic event (TEE) within 3 months prior to surgery
7. History of severe allergic reactions to PCC or FP
8. Individuals who have immunoglobulin A (IgA) deficiency with known antibodies against IgA
9. Refusal of allogeneic blood products
10. Known pregnancy
11. Currently enrolled in other interventional clinical trials

Primary outcomes:
measure: Number of patients requiring additional hemostatic intervention
timeFrame: 60 minutes to 24 hours after first dose of IMP
Secondary outcomes:
measure: Number of patients requiring additional hemostatic intervention based on hemoglobin level
timeFrame: 60 minutes to 24 hours after first dose of IMP
measure: Compare the amount of chest tube drainage between the Octaplex and FP groups.
timeFrame: 12 and 24 hours after chest closure
measure: 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).
timeFrame: 24 hours after surgery start, after the end of CPB and after IMP initiation
measure: Compare efficacy in terms of the mean number of total allogeneic blood components (IMP and non-IMP) transfused between the Octaplex and FP groups.
timeFrame: First 24 hours after the end of CPB
measure: Compare efficacy in terms of the mean number of total non-IMP allogeneic blood components transfused between the Octaplex and FP groups.
timeFrame: First 24 hours after the end of CPB
measure: Compare efficacy in terms of the mean number of total non-IMP allogeneic blood components transfused between the Octaplex and FP groups.
timeFrame: First 24 hours and 7 days after imp initiation
measure: Compare mean number of individual allogeneic blood components transfused between the Octaplex and FP groups.
timeFrame: 24 hours and 7 days after start of surgery, and after the end of CPB and after IMP initiation
measure: Compare efficacy in terms of the incidence of transfusion of individual allogeneic blood components transfused between the Octaplex and FP groups.
timeFrame: 24 hours and 7 days after start of surgery and after the end of CPB and after IMP initiation
measure: Compare incidence of administration of non-IMP coagulation factor products between Octaplex and FP groups
timeFrame: 24 hours and 7 days after the start of surgery, after the end of CPB and after IMP initiation
measure: Compare incidence of intracerebral hemorrhage between the Octaplex and FP groups
timeFrame: 24 hours after start of surgery, after the end of CPB and after IMP initiation
measure: Compare incidence of gastrointestinal hemorrhage between Octaplex and FP groups
timeFrame: 24 hours after start of surgery, after the end of CPB and after IMP initiation
measure: Compare incidence of surgical re-exploration between Octaplex and FP groups
timeFrame: 24 hours after start of surgery, after the end of CPB and after IMP initiation
measure: Compare the effect of Octaplex versus FP administration on the change in international normalised ratio (INR) before and after therapy administration.
timeFrame: Within 30 minutes before to within 60 minutes after the initiation of IMP administration.
measure: Compare the effect of Octaplex versus FP administration on Prothrombin Time (PT)
timeFrame: Within 75 minutes before to within 75 minutes after the initiation of IMP administration
measure: Compare the effect of Octaplex versus FP administration on aPTT
timeFrame: Within 75 minutes before to within 75 minutes after the initiation of IMP administration
measure: Compare the effect of Octaplex versus FP administration on fibrinogen activity
timeFrame: Within 75 minutes before to within 75 minutes after the initiation of IMP administration
measure: Compare the effect of Octaplex versus FP administration on ROTEM EXTEM CT
timeFrame: Within 75 minutes before to within 75 minutes after the initiation of IMP administration
measure: Compare the effect of Octaplex versus FP administration on ROTEM EXTEM MCT
timeFrame: Within 75 minutes before to within 75 minutes after the initiation of IMP administration
measure: Compare the effect of Octaplex versus FP administration on ROTEM FIBTEM MCF
timeFrame: Within 75 minutes before to within 75 minutes after the initiation of IMP administration
measure: Compare the effect of Octaplex versus FP administration on platelets
timeFrame: Within 75 minutes before to within 75 minutes after the initiation of IMP administration
measure: Compare total time elapsed from initiation of the first dose of IMP to arrival at the ICU room between the Octaplex and FP groups.
timeFrame: From initiation of IMP to arrival at ICU room (within 24 hours)
measure: Comparison of incidence of serious treatment-emergent adverse events between Octaplex and FP groups
timeFrame: From the beginning of surgery up to postoperative day 30
measure: Comparison of the duration of mechanical ventilation between Octaplex and FP groups
timeFrame: From the beginning of surgery up to postoperative day 30
measure: Comparison of the duration of ICU stay between Octaplex and FP groups
timeFrame: From the beginning of surgery up to postoperative day 30
measure: Comparison of the duration of hospitalization between Octaplex and FP groups
timeFrame: From the beginning of surgery up to postoperative day 30
measure: Comparison of the incidence of death between Octaplex and FP groups
timeFrame: From the beginning of surgery up to postoperative day 30
measure: Comparison of the number of days alive and out of hospital between Octaplex and FP groups
timeFrame: From the beginning of surgery up to postoperative day 30
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: New Westminster
country: Canada
facility: Royal Columbian Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: University of British Columbia and Vancouver Coastal Health Authority
state: British Columbia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Corporation
state: Ontario
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Hospital
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Montréal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Québec
country: Canada
facility: Quebec Laval
state: Quebec
Study officials:
References: