Health Canada approves new cardiac-surgery indication for Octaplex®, based on evidence generated in Canada

Health Canada has approved an updated Product Monograph for Octaplex® (Human Prothrombin Complex), adding an indication for the treatment of bleeding in acquired deficiency of prothrombin-complex coagulation factors, including the deficiency that occurs during cardiac surgery. The Monograph also revises dosing and administration guidance for the existing vitamin K antagonist (VKA) indication.

The new indication rests on FARES-II, a Phase 3 randomized controlled trial conducted predominantly in Canada and published in JAMA in May 2025. It is the endpoint of a research program that began with a single-centre pilot at Toronto General Hospital and grew into a multicentre trial run through Canadian academic hospitals with Canadian public research funding.

What the trial found

FARES-II randomised 420 patients between November 2022 and May 2024 across twelve hospitals, ten of them Canadian and including centres in Ontario and Quebec; approximately 95 per cent of participants were enrolled in Canada. Seventy per cent underwent complex procedures. The trial was co-sponsored by the Canadian Institutes of Health Research and Octapharma, and co-led by Dr Keyvan Karkouti at University Health Network and Dr Jeannie Callum at Kingston Health Sciences Centre and Queen’s University.

Bleeding was controlled without the need for further intervention in 77.9 per cent of patients treated with prothrombin complex concentrate, compared with 60.4 per cent of those treated with frozen plasma — a difference of 17.6 percentage points, meeting both non-inferiority and superiority thresholds. Patients in the concentrate group received fewer allogeneic units in the following 24 hours, at an average of 6.6 units against 9.3, counting red cells, platelets and non-study plasma together.

The practical difference in administration was substantial. The first dose of concentrate averaged 99 millilitres and was completed in a median of seven minutes. The first dose of frozen plasma averaged 811 millilitres — more than eight times the volume — and took a median of 26 minutes to complete.

Serious adverse events occurred in 36.2 per cent of the concentrate group against 47.3 per cent of the plasma group. Acute kidney injury, a common complication after cardiopulmonary bypass, occurred in 10.3 per cent against 18.8 per cent. Thromboembolic events did not differ significantly, at 8.5 per cent against 7.2 per cent, and deaths were seven and eight respectively

“The efficacy result was what we set out to test. The safety result was the one that intrigued us the most: fewer serious adverse events, and about half the rate of acute kidney injury, without any excess of thrombotic events. Our working explanation is straightforward: controlling bleeding faster means less blood loss and fewer transfusions, which translates to fewer complications that come with blood loss and transfusion. The Product Monograph change is important because it helps clinicians make it part of their routine practice for bleeding management. They no longer have to reason by analogy from a paper. The dose, the population and the monitoring are now written down."

— said Dr. Keyvan Karkouti, Principal Investigator of the FARES-II trial.

Implications for the Canadian blood system

Frozen plasma must be thawed and matched to blood group before it can be given. A prothrombin complex concentrate is stored ready to use, is pathogen-reduced and does not require blood-group matching. In a system where every unit of plasma originates with a donor, the trial’s reduction in allogeneic component use speaks directly to the objectives of Patient Blood Management, the international standard that treats a patient’s own blood as a resource to be conserved rather than replaced.

“FARES-II wasn't about replacing plasma for all patients - it studied bleeding in patients after cardiopulmonary bypass, which is the most common use of plasma in many jurisdictions. Used in this context, the case is compelling: better haemostatic control, fewer red cell and platelet units, less kidney injury, less costs to care, and a product that's ready in minutes - no thawing, no blood-group matching. In a system where every unit of plasma is a donation, that's real stewardship. The numbers back it up: a 29% reduction in allogeneic blood product use in the trial. Prothrombin Complex Concentrate is a major innovation for the care of the bleeding cardiac surgery patient.”

— said Dr Jeannie Callum, Principal Investigator of the FARES-II trial.

“Many transfusion experts have long believed and practiced that the use of prothrombin complex concentrates like Octaplex, produces better outcomes for bleeding cardiac surgery patients.  Octaplex in this setting is also advantageous since time means lives saved, where thawing plasma would take anywhere from 30 minutes to an hour which is not appropriate for surgical bleeding. For the blood bank, we also don’t need to match blood groups, be limited by freezer space or thawers, or be practically concerned about transfusion-transmitted infection. I believe the FARES-II study and the subsequent label change now gives everyone the rationale to support current best practice as routine policy.”

— said Dr. Andrew Shih, Regional Director, Transfusion Medicine, Hamilton Regional Laboratory Medicine Program.

A within-trial economic evaluation led at University Health Network and presented at the Canadian Society for Transfusion Medicine Annual Conference in May 2026 assessed 152 FARES-II participants from one Canadian centre from a health-system payer perspective. In this preliminary analysis, the concentrate was both more effective and less costly in 91 per cent of bootstrap samples, with an estimated average reduction in 30-day hospital costs of $7,952 per patient. Analyses using the full trial dataset are ongoing.

FARES-II was an open-label trial, and its accompanying JAMA editorial noted that neither mortality nor length of stay differed between groups. The approved indication covers targeted factor replacement in patients with documented or suspected deficiency, rather than routine substitution for plasma.

Updated dosing and infusion speed guidance

For the new cardiac-surgery indication, the approved dose is 1,500 IU for patients weighing 60 kg or less and 2,000 IU for patients above 60 kg, with one repeat dose if required, infused at approximately 15 mL/min to a maximum of 20 mL/min.

The existing indication for VKA-associated bleeding and perioperative prophylaxis is retained, with dosing based on pre-treatment INR and body weight: 25 IU/kg for INR 2 to below 4, 35 IU/kg for INR 4 to 6, and 50 IU/kg for INR above 6. The maximum single dose is now 2,500 IU, 3,500 IU or 5,000 IU according to pre-treatment INR, with the maximum for INR above 6 raised to 5,000 IU from the previous limit of 3,000 IU. The approved infusion rate is 0.12 mL/kg/min, to a maximum of 8 mL/min.

"Ten years ago, this began as a single question asked at one Toronto hospital. It became a trial across ten Canadian centres, funded alongside the Canadian Institutes of Health Research, designed by Canadian investigators, and answered on Canadian patients. We did not bring this evidence to Canada; it was built here. The most durable thing a company can contribute to a health system is not a product but a question properly answered, and once that answer is in a Product Monograph, it belongs to every clinician in the country. That is also the step from evidence to practice, and it is where Patient Blood Management in this country has often stalled for want of Canadian data. Our contribution has been to help supply that data, at scale, in the settings where the decisions are actually made. We intend to keep doing”

— said Sri Adapa, General Manager, Octapharma Canada.

For complete prescribing information, including indications, contraindications, warnings and precautions, consult the Octaplex® Product Monograph.

About Octaplex®

Octaplex® (Human Prothrombin Complex) is a plasma-derived, four-factor prothrombin complex concentrate.

About Octapharma Canada

For over two decades, Octapharma Canada has worked alongside Canadian clinicians, blood operators, and institutions to help improve how bleeding is managed in surgery, trauma, and pre-hospital care.

Through well-powered clinical studies and four pathogen-safe factor concentrates, the company has contributed to a shift away from traditional transfusion toward more precise, evidence-based approaches — supported by products designed to work in and outside the hospital through room temperature storage, long shelf life, and rapid preparation.

Media Contact

Sri Adapa

General Manager, Octapharma Canada

info.canada@octapharma.com

References:

^{1.  Octaplex® Product Monograph. Octapharma Canada Inc., August 2026.}

^{2.  Karkouti K, Callum JL, Bartoszko J, et al. Prothrombin Complex Concentrate vs Frozen Plasma for Coagulopathic Bleeding in Cardiac Surgery: The FARES-II Multicenter Randomized Clinical Trial. JAMA. 2025;333(20):1781–1792. doi:10.1001/jama.2025.3501}

^{3.  Karkouti K, Bartoszko J, Grewal D, et al. 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;4(4):e213936.}

^{4.  Abrahamyan L, Best N, Sahakyan Y, et al. Cost-Effectiveness of Prothrombin Complex Concentrate versus Frozen Plasma for Coagulopathic Bleeding in Cardiac Surgery: Economic Evaluation of the FARES-II RCT. Presented at the Canadian Society for Transfusion Medicine Annual Conference, 26 May 2026.}

^{5.  Wang R, Bennett-Guerrero E. Is it time to replace plasma with prothrombin complex concentrate in cardiac surgery? JAMA. 2025. [Accompanying editorial.]}