Active-control Randomized Trial Comparing 4-factor Prothrombin Complex Concentrate With Frozen Plasma in Cardiac Surgery

NCT05523297 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: LEX-211
• Study Type: interventional
• Target: 420
• Locations: 2 countries
• Sites: 13

Brief Summary

This is a multicenter, active-control randomized, prospective, Phase 3 study in adult cardiac surgery patients. 420 patients were randomized at 12 hospitals.

Conditions

Bleeding Cardiac Surgery Patients

Outcome Measures

Primary Outcomes (1)

• Number of Patients Requiring Additional Hemostatic Intervention

  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 \[rFVIIa\], 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.

  60 minutes to 24 hours after first dose of IMP

Secondary Outcomes (28)

• Comparison of Global Hemostatic Response Based on Requirement of Additional Hemostatic Intervention and Decreased Hemoglobin Levels

  60 minutes to 24 hours after first dose of IMP

• Compare the Amount of Chest Tube Drainage Between the Octaplex and FP Groups.

  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).

  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 Products (ABPs) (IMP and Non-IMP) Transfused Between the Octaplex and FP Groups.

  First 24 hours after the end of CPB

• Compare Efficacy in Terms of the Mean Number of Total Non-IMP Allogeneic Blood Products Transfused Between the Octaplex and FP Groups.

  First 24 hours after the end of CPB

Study Arms (2)

Octaplex

EXPERIMENTAL

Participants were administered Octaplex according to a recommended initial dose of 1,500 IU for patients weighing ≤60 kg and 2,000 IU for patients weighing \>60 kg. A second dose of IMP could be administered if the patient continued to have at least moderate bleeding and suspected coagulation deficiency (e.g., INR ≥1.5) after completion of the first dose, up to the maximum allowable dose (3,000 IU if ≤60 kg or 4,000 IU if \>60 kg). Octaplex: Prothrombin complex concentrate

Drug: Octaplex

Frozen plasma

ACTIVE COMPARATOR

Participants were administered FP according to a recommended initial dose of 3 U for patients weighing ≤60 kg and 4 U for patients weighing \>60 kg. A second dose of IMP could be administered if the patient continued to have at least moderate bleeding and suspected coagulation deficiency (e.g., INR ≥1.5) after completion of the first dose, up to the maximum allowable dose (6 U if ≤60 kg or 8 U if \>60 kg). Frozen Plasma Product, Human

Drug: Frozen Plasma Product, Human

Interventions

Octaplex DRUG

Prothrombin complex concentrate

Octaplex

Frozen Plasma Product, Human DRUG

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

Frozen plasma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Octapharma: lead

Study Sites (13)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Royal Columbian Hospital

New Westminster, British Columbia, V3L 3W7, Canada

Location

University of British Columbia and Vancouver Coastal Health Authority

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Hamilton Health Sciences Corporation

Hamilton, Ontario, L8L 8E7, Canada

Location

Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

London Health Sciences

London, Ontario, N6A 5A5, Canada

Location

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

Location

Sunnybrook Hospital

Toronto, Ontario, M4N 3M5, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

Location

Quebec Laval

Québec, Quebec, G1V 4G5, Canada

Location

Related Publications (2)

• Karkouti K, Callum JL, Bartoszko J, Tanaka KA, Knaub S, Brar S, Ghadimi K, Rochon A, Mullane D, Couture EJ, Lin Y, Harle C, Zeller M, Tran DTT, Solomon C, Rao V, Law M, Butt AL, Chen EP, Martins MR, Saha T, Shih AW, Vezina MC, Moussa F, Pereira Cezar Zamper R, Syed S, Buyukdere H, Werner S, Grewal D, Wong D, Vandyck KB, Tanzola R, Hughes B, Royer O, Wong S, Levy JH; FARES-II Study Group. Prothrombin Complex Concentrate vs Frozen Plasma for Coagulopathic Bleeding in Cardiac Surgery: The FARES-II Multicenter Randomized Clinical Trial. JAMA. 2025 May 27;333(20):1781-1792. doi: 10.1001/jama.2025.3501.

  PMID: 40156829 DERIVED

• Karkouti K, Callum J, Bartoszko J, Solomon C, Knaub S, Levy JH, Tanaka KA; FARES-II Study Group. Protocol for a phase 3, randomised, active-control study of four-factor prothrombin complex concentrate versus frozen plasma in bleeding adult cardiac surgery patients requiring coagulation factor replacement: the LEX-211 (FARES-II) trial. BMJ Open. 2024 Aug 21;14(8):e091381. doi: 10.1136/bmjopen-2024-091381.

  PMID: 39174056 DERIVED

MeSH Terms

Interventions

prothrombin complex concentrates

Results Point of Contact

• Title: Dr Keyvan Karkouti
• Organization: Toronto General Hospital

keyvan.karkouti@uhn.ca

(416) 340-8597

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Given the physical differences in the products and the emergency nature of the intervention, attending clinicians present during the infusion of the blood products/components were not blinded to the treatment. To minimize bias, treating clinicians were blinded to group assignments until immediately prior to IMP infusion. The sponsor and data management teams were also blinded to treatment group allocations
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2022
• First Posted: August 31, 2022
• Study Start: November 30, 2022
• Primary Completion: June 27, 2024
• Study Completion: June 27, 2024
• Last Updated: August 15, 2025
• Results First Posted: August 15, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (11); US (2)