Factor Replacement in Surgery

NCT ID: NCT04114643

Last Updated: 2020-11-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

103 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-09-24

Study Completion Date

2020-12-31

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.

Detailed Description

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Conditions

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Bleeding in Cardiac Surgery

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

OTHER

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Prothrombin Complex Concentrate

Group Type ACTIVE_COMPARATOR

Prothrombin Complex Concentrate

Intervention Type BIOLOGICAL

Octaplex will be administered when the blood bank receives an order for coagulation factor replacement

Frozen Plasma

Group Type ACTIVE_COMPARATOR

Frozen Plasma

Intervention Type BIOLOGICAL

Frozen Plasma will be administered when the blood bank receives an order for coagulation factor replacement

Interventions

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Prothrombin Complex Concentrate

Octaplex will be administered when the blood bank receives an order for coagulation factor replacement

Intervention Type BIOLOGICAL

Frozen Plasma

Frozen Plasma will be administered when the blood bank receives an order for coagulation factor replacement

Intervention Type BIOLOGICAL

Other Intervention Names

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Octaplex Fresh Frozen Plasma

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:

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Health Network, Toronto

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Keyvan Karkouti, MD

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Locations

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Sunnybrook Health Science Centre

Toronto, Ontario, Canada

Site Status

Countries

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Canada

References

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Hayes K, Fernando MC, Jordan V. Prothrombin complex concentrate in cardiac surgery for the treatment of coagulopathic bleeding. Cochrane Database Syst Rev. 2022 Nov 21;11(11):CD013551. doi: 10.1002/14651858.CD013551.pub2.

Reference Type DERIVED
PMID: 36408876 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33792729 (View on PubMed)

Other Identifiers

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19-5393

Identifier Type: -

Identifier Source: org_study_id