1. 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
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Éric Dumont, Lusine Abrahamyan, Stuart Mccluskey, Angela Jerath, Humara Poonawala, Andrew Stevens, Jeannie Callum, Alan Tinmouth, Daniel Wong, Gianluigi Bisleri, Tarit Saha, David Mazer, Hilary Grocott, Jane Yang, Jeff Kinney, Yoan Lamarche, Damon Scales, George Tomlinson, Fuad Moussa, Andrew Shih, Michelle Zeller, Melanie Tokessy, Keyvan Karkouti, Vivek Rao, Summer Syed, Lilia Kaustov, Sophia Wong, Lani Lieberman, Kamrouz Ghadimi, Philippe Demers, Penny Johnson, Jerrold H Levy, Justyna Bartoszko, Miki Peer, Michael Law, Michelle Wong, Mackenzie Quantz, Antoine Rochon, Fraser Rubens, Shagun Jain, Yulia Lin, Katerina Pavenski, Deep Grewal, Deborah DuMerton, Darrin Payne, Saba Ansari, Robert Mayer, Rebecca Randall, Aftab Malik, Bethany Smethurst, Laura Molnar, Angela Sirosky-Yanyk, Mark Peterson, Christopher Harle, Etienne Couture, Diem Tran, Cristina Solomon, Sigurd Knaub, Kenichi A Tanaka, Blaine Achen, Sukhpal Brar, Matthew Coley, Dana Devine, Alana Flexman, Camila Machado de Souza, Maria Rosal Martins, Terri Sun, Rob Tanzola, Mathew Yan, Raffael Zamper, Jo Carrol, Nishanthi Liyanage, Simryn Selby, Reezanoor Kabir, Shelley Oliver, Alioska Escorcia, Susana Medic, Michelle Mozel, Ramanjot Kaur, Kelly Bizovie, Sarah Buchko, Raven Arly Gonzales, Korey Sutherland, Jenna Van Roekel, Alveena Babul, Ken Tanaka, Kofi Vandyck, Amir Butt, Hisako Okada, Robert Tanzola, Reegan Tod, Aiden Scholey, Wafaa Haider, Ester Cisneros-Aguilera, Alexandre Bergeron, Genevieve Belanger, Darren Mullane, Bevan Hughes, Sakara Hutspardol, Shirley Lim, Jian Mi, Debbie Kalar, Matthew Eang, Erick Lorenzana-Saldivar, Edward P Chen, Akash Gupta, Philip Lau, Pablo Perez D’Empaire, Chantal Armali, Amie Malkin, Connie Colavecchia, Harley Meirovich, Annie Bergeron, Francois Laforge, Kim Paradis, Nathalie Gagne, Marie Soleil Saillant, Marie-Claude Vézina, Olivier Royer, Marie-Ève Charest, Lee-Anne Fochesato, Yuxin Bai, Iqbal Jaffar, Nour Alhomsi, Janine Guevarra, Erin Jamula, Wan Chien (Betty) Hsu, Abbey Drew, Hakan Buyukdere, Drashtee Patel, Elizabeth Watt, Hadia Arabi Katbi, Kim Luciano, Amy Moorehead, Kamola Kasimova, Farzana Tasmin, Cielo Bingley, Victoria Barkley, Tob Reegan, Marianna Qu, Jessica Xiong, Sophie Robichaud, Christy Peterson, Manu Jairath, Mathew Tang, Jennita Aariaratnam, Leron DuMerton, Lucas Drew, Sahrish Masood, Toni Tidy, and Elizabeth Krok
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Medicine - Abstract
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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- 2024
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