Active-control Randomized Trial Comparing 4-factor Prothrombin Complex Concentrate With Frozen Plasma in Cardiac Surgery (FARES-2)

Octapharma

Status and phase: Completed; Phase 3

Conditions: Bleeding Cardiac Surgery Patients

Treatments: Drug: Frozen Plasma Product, Human; Drug: Octaplex

Study type: Interventional

Funder types: Industry

Identifiers

NCT05523297

LEX-211

Details and patient eligibility

About

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

Full 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.

Enrollment: 420 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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420 participants in 2 patient groups

Octaplex

Experimental group

Description:

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

Treatment:

Drug: Octaplex

Frozen plasma

Active Comparator group

Description:

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

Treatment:

Drug: Frozen Plasma Product, Human