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

NCT ID: NCT05523297

Last Updated: 2025-08-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 420 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-30
• Study Completion Date: 2024-06-27

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.

Detailed Description

Patients were randomized to receive either 4-factor PCC (Octaplex) or frozen plasma (FP). The study compared 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 includes adult (≥18 years old) patients who underwent cardiac surgery with cardiopulmonary bypass (CPB) and required 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.

Conditions

Bleeding Cardiac Surgery Patients

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Octaplex

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

Group Type: EXPERIMENTAL

Octaplex

Intervention Type: DRUG

Prothrombin complex concentrate

Frozen plasma

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

Group Type: ACTIVE_COMPARATOR

Frozen Plasma Product, Human

Intervention Type: 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

Interventions

Octaplex

Prothrombin complex concentrate

Intervention Type: DRUG

Frozen Plasma Product, Human

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

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Octapharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Duke University Health System

Durham, North Carolina, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Royal Columbian Hospital

New Westminster, British Columbia, Canada

University of British Columbia and Vancouver Coastal Health Authority

Vancouver, British Columbia, Canada

Hamilton Health Sciences Corporation

Hamilton, Ontario, Canada

Kingston General Hospital

Kingston, Ontario, Canada

London Health Sciences

London, Ontario, Canada

University of Ottawa Heart Institute

Ottawa, Ontario, Canada

Sunnybrook Hospital

Toronto, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

Toronto General Hospital

Toronto, Ontario, Canada

Montreal Heart Institute

Montreal, Quebec, Canada

Quebec Laval

Québec, Quebec, Canada

Countries

United States; Canada

References

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.

Reference Type: DERIVED

PMID: 40156829 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39174056 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

LEX-211

Identifier Type: -

Identifier Source: org_study_id