Clinical trial NCT04114643: Factor Replacement in Surgery
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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Bleeding in Cardiac Surgery
Keywords: Frozen Plasma (FP)
Prothrombin Complex Concentrate (PCC)
Octaplex
Coagulation Factor Replacement
Transfusion
Bleeding Cardiac Surgical Patients
Pilot
Phase 2
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2019-10-03
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: OTHER

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.


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:

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

Primary outcomes:
measure: Treatment response
timeFrame: At 4 and 24 hours
measure: Amount of allogeneic blood products
timeFrame: 24 hours after the start of surgery
measure: Number of patients who do not receive any RBC transfusions or any allogeneic blood transfusions
timeFrame: first 24 hours after the start of surgery
Secondary outcomes:
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Sunnybrook Health Science Centre
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Keyvan Karkouti, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.