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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.

Publication ,  Journal Article
Karkouti, K; Callum, J; Bartoszko, J; Solomon, C; Knaub, S; Levy, JH; Tanaka, KA; FARES-II Study Group
Published in: BMJ Open
August 21, 2024

INTRODUCTION: Reduced thrombin generation is an important component of post cardiopulmonary bypass (CPB) coagulopathy. To replenish coagulation factors and enhance thrombin generation in bleeding surgical patients, frozen plasma (FP) and four-factor prothrombin complex concentrate (4F-PCC) are used. However, the efficacy-safety balance of 4F-PCC relative to FP in cardiac surgery is unconfirmed. METHODS AND ANALYSIS: LEX-211 (FARES-II) is an active-control, randomised, phase 3 study comparing two coagulation factor replacement therapies in bleeding adult cardiac surgical patients at 12 hospitals in Canada and the USA. The primary objective is to determine whether 4F-PCC (Octaplex/Balfaxar, Octapharma) is clinically non-inferior to FP for haemostatic effectiveness. Inclusion criteria are any index (elective or non-elective) cardiac surgery employing CPB and coagulation factor replacement with 4F-PCC or FP ordered in the operating room for bleeding management. Patients will be randomised to receive 1500 or 2000 international units of 4F-PCC or 3 or 4 units of FP, depending on body weight. The primary endpoint of haemostatic treatment response is 'effective' if no additional haemostatic intervention is required from 60 min to 24 hours after the first initiation of 4F-PCC or FP; or 'ineffective' if any other haemostatic intervention (including a second dose of study drug) is required. An estimated 410 evaluable patients will be required to demonstrate non-inferiority (one-sided α of 0.025, power ≥90%, non-inferiority margin 0.10). Secondary outcomes include transfusions, bleeding-related clinical endpoints, coagulation parameters and safety. ETHICS AND DISSEMINATION: The trial has been approved by the institutional review boards of all participating centres. Trial completion is anticipated at the end of 2024, and results will be disseminated via publications in peer-reviewed journals and conference presentations in 2025. The results will advance our understanding of coagulation management in bleeding surgical patients, potentially reducing the need for allogeneic blood products and improving outcomes in surgical patients. TRIAL REGISTRATION NUMBER: NCT05523297.

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Published In

BMJ Open

DOI

EISSN

2044-6055

Publication Date

August 21, 2024

Volume

14

Issue

8

Start / End Page

e091381

Location

England

Related Subject Headings

  • United States
  • Postoperative Hemorrhage
  • Plasma
  • Humans
  • Hemostatics
  • Clinical Trials, Phase III as Topic
  • Cardiopulmonary Bypass
  • Cardiac Surgical Procedures
  • Canada
  • Blood Coagulation Factors
 

Citation

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Karkouti, K., Callum, J., Bartoszko, J., Solomon, C., Knaub, S., Levy, J. H., … FARES-II Study Group. (2024). 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, 14(8), e091381. https://doi.org/10.1136/bmjopen-2024-091381
Karkouti, Keyvan, Jeannie Callum, Justyna Bartoszko, Cristina Solomon, Sigurd Knaub, Jerrold H. Levy, Kenichi A. Tanaka, and 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 14, no. 8 (August 21, 2024): e091381. https://doi.org/10.1136/bmjopen-2024-091381.

Published In

BMJ Open

DOI

EISSN

2044-6055

Publication Date

August 21, 2024

Volume

14

Issue

8

Start / End Page

e091381

Location

England

Related Subject Headings

  • United States
  • Postoperative Hemorrhage
  • Plasma
  • Humans
  • Hemostatics
  • Clinical Trials, Phase III as Topic
  • Cardiopulmonary Bypass
  • Cardiac Surgical Procedures
  • Canada
  • Blood Coagulation Factors