Randomized Controlled Trial

. 2024 Oct 22;150(17):1315-1323.

doi: 10.1161/CIRCULATIONAHA.124.069606. Epub 2024 Apr 8.

Topical Versus Intravenous Tranexamic Acid in Patients Undergoing Cardiac Surgery: The DEPOSITION Randomized Controlled Trial

André Lamy^{1

2}, Dmitry A Sirota³, Frederic Jacques⁴, Ahmad Poostizadeh⁵, Nicolas Noiseux⁶, Sergey Efremov⁷, Philippe Demers⁸, Boris Akselrod⁹, Chew Yin Wang¹⁰, Rakesh C Arora^{11

12}, Piotr Branny¹³, Shay P McGuinness¹⁴, Craig D Brown¹⁵, Hugues Jeanmart¹⁶, Qiang Zhao^{17

18}, Haibo Zhang¹⁹, Emilie P Belley-Côté^{1

20}, Richard P Whitlock^{1

2}, Austin Browne²¹, Ingrid Copland¹, Jessica Vincent¹, Rutaba Khatun¹, Kumar Balasubramanian¹, Shrikant I Bangdiwala^{1

22}, Michael H McGillion^{1

23}, Alison E Fox-Robichaud^{20

24}, Jessica Spence^{1

22

25}, Salim Yusuf^{1

20}, P J Devereaux; DEPOSITION Study Group^{1

22

20}

Collaborators, Affiliations

Collaborators

DEPOSITION Study Group:
Hyla Peens-Hough, Keri-Anne Crowdrey, Rachael Parke, Shay McGuinness, Jiangang Wang, Sheng Wang, Nicolas Noiseux, Jessica Forcillo, Joannie Dionne, Joe Helou, Louis Mathieu Stevens, Virginie Cote-Gravel, Alexander Boboshko, Alexander Bogachev-Prokophiev, Alexey Fomichev, Andrey Protopopov, Dmitry Sirota, Dmitry Khvan, Elena Kliver, Galina Mankevich, Kaisar Kaldar, Maxim Lyashenko, Sergey Alsov, Vladimir Lomivorotov, Ali Alsagheir, Diane Lourenco, Dominic Parry, Iqbal Jaffer, Lloyd Semelhago, Michelle Isac, Mike Zhu, Natalie Ricotta, Nayer Youssef, Patricia Power, Tomas Vanhelder, Victor Chu, Austin Browne, Rakesh Arora, Angela Nauleau Javaudin, Angélica Ostiguy, Clément Schneider, Annie Bergeron, Dimitri Kalavrouziotis, Éric Dumont, Éric Charbonneau, Etienne Couture, François Dagenais, François Dagenais, François Laforge, Frederic Jacques, Maxime Laflamme, Mohamed Marzouk, Nathalie Gagné, Pierre Voisine, Siamak Mohammadi, Ahmad Poostizadeh, Alissa Smith, Calvin Wan, Costas Schulze, Jia Lin Soon, Keerit Tauh, Osama Ben Hameid, Richard Saczkowski, Alison E. Fox-Robichaud, Antoine Rochon, Denis Bouchard, Lebon Jean-Sébastien, Louis Perrault, Michel Pellerin, Philippe Demers, Pierre-Emmanuel Noly, Sebastian Andrés Parisi, Yoan Lamarche, Petr Kacer, Vladimir Buzalka, Dominik Petrovič, Filip Glac, Štefan Michut, Chris White, Craig D. Brown, Ivan Zalentsov, Jf Legare, Boris Akselrod, Andrey Lysenko, Artem Gubko, Denis Guskov, Ekaterina Tereshchenko, Evgeny Evseev, Olga Lipatova, Pavel Lednev, Emily Dai, Eric Deng, Gianluca Rigitano, Ingrid Copland, Jessica Vincent, Kumar Balasubramanian, Louay Habbab, Martin Renters, Nikki Pinder, Rutaba Khatun, Sarah Apolcer, Tahsin Ferdous, Yongning Ou, André Lamy, Emilie P. Belley-Côté, Fei Yuan, Jessica Spence, Michael H. McGillion, Pj Devereaux, Richard P. Whitlock, Salim Yusuf, Shrikant I. Bangdiwala, Joel Parlow, Rene Allard, Yiwei Xu, Yun Liu, Yunpeng Zhu, Anastasia V. Shudra, Artem V. Tolstykh, Dmitry V. Shmatov, Elizaveta A. Leonova, Nikita S. Popkov, Oleg B. Povodish, Polina N. Turina, Sergey Efremov, David Kent, Marnie Boyle, Michael Yamashita, Mullein Thorleifson, Nitin Ghorpade, Stephen Fremes, Ashvin K. Nair, Chew Yin Wang, Mohd Fitry Zainal Abidin, Noorjahan H. Md Hashim, Shahrul A. Hashim, Sivakumar Krishnasamy, Bernard McDonald, Dean Fergusson, Fraser Rubens, Dave Nagpal

Affiliations

¹ Population Health Research Institute, Hamilton, ON, Canada (A.L., E.P.B-C., R.P.W., I.C., J.V., R.K., K.B., S.I.B., M.H.M., J.S., S.Y., P.J.D.).
² Surgery (A.L., R.P.W.), McMaster University, Hamilton, ON, Canada.
³ E. Meshalkin National Medical Research Center, Novosibirsk, Russia (D.A.S.).
⁴ Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Canada (F.J.).
⁵ Kelowna General Hospital, BC, Canada (A.P.).
⁶ Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), QC, Canada (N.N.).
⁷ Saint Petersburg State University Hospital, Russia (S.E.).
⁸ Montreal Heart Institute, University of Montréal, QC, Canada (P.D.).
⁹ Petrovsky National Centre of Surgery, Moscow, Russia (B.A.).
¹⁰ Department of Anesthesiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia (C.Y.W.).
¹¹ Division of Cardiac Surgery, University Hospitals Harrington Heart and Vascular Institute, Cleveland, OH (R.C.A.).
¹² Department of Surgery, Case Western Reserve University, Cleveland, OH (R.C.A.).
¹³ Department of Cardiac Surgery, Hospital Agel Trinec-Podlesi, Trinec, Czech Republic (P.B.).
¹⁴ Auckland City Hospital, New Zealand (S.P.M.).
¹⁵ New Brunswick Heart Centre, Saint John, Canada (C.D.B.).
¹⁶ Centre Intégré Universitaire de Santé et de Services Sociaux du Nord-de-l'Île-de-Montréal, Hôpital du Sacré-Coeur de Montréal, QC, Canada (H.J.).
¹⁷ Rujin Hospital, Shanghai, China (Q.Z.).
¹⁸ Shanghai Jiao Tong University School of Medicine, China (Q.Z.).
¹⁹ Beijing Anzhen Hospital, China (H.Z.).
²⁰ Medicine (E.P.B-C., A.E.F-B., S.Y., P.J.D.), McMaster University, Hamilton, ON, Canada.
²¹ Hamilton Health Sciences, Hamilton General Hospital, Ontario, Canada (A.B.).
²² Departments of Health Research Methods, Evidence, and Impact (S.I.B., J.S., P.J.D.), McMaster University, Hamilton, ON, Canada.
²³ School of Nursing (M.H.M.), McMaster University, Hamilton, ON, Canada.
²⁴ Thrombosis and Atherosclerosis Research Institute (A.E.F-B.), McMaster University, Hamilton, ON, Canada.
²⁵ Anesthesia (J.S.), McMaster University, Hamilton, ON, Canada.

PMID: 38587333
DOI: 10.1161/CIRCULATIONAHA.124.069606

Randomized Controlled Trial

Topical Versus Intravenous Tranexamic Acid in Patients Undergoing Cardiac Surgery: The DEPOSITION Randomized Controlled Trial

André Lamy et al. Circulation. 2024.

. 2024 Oct 22;150(17):1315-1323.

doi: 10.1161/CIRCULATIONAHA.124.069606. Epub 2024 Apr 8.

Authors

Collaborators

DEPOSITION Study Group:
Hyla Peens-Hough, Keri-Anne Crowdrey, Rachael Parke, Shay McGuinness, Jiangang Wang, Sheng Wang, Nicolas Noiseux, Jessica Forcillo, Joannie Dionne, Joe Helou, Louis Mathieu Stevens, Virginie Cote-Gravel, Alexander Boboshko, Alexander Bogachev-Prokophiev, Alexey Fomichev, Andrey Protopopov, Dmitry Sirota, Dmitry Khvan, Elena Kliver, Galina Mankevich, Kaisar Kaldar, Maxim Lyashenko, Sergey Alsov, Vladimir Lomivorotov, Ali Alsagheir, Diane Lourenco, Dominic Parry, Iqbal Jaffer, Lloyd Semelhago, Michelle Isac, Mike Zhu, Natalie Ricotta, Nayer Youssef, Patricia Power, Tomas Vanhelder, Victor Chu, Austin Browne, Rakesh Arora, Angela Nauleau Javaudin, Angélica Ostiguy, Clément Schneider, Annie Bergeron, Dimitri Kalavrouziotis, Éric Dumont, Éric Charbonneau, Etienne Couture, François Dagenais, François Dagenais, François Laforge, Frederic Jacques, Maxime Laflamme, Mohamed Marzouk, Nathalie Gagné, Pierre Voisine, Siamak Mohammadi, Ahmad Poostizadeh, Alissa Smith, Calvin Wan, Costas Schulze, Jia Lin Soon, Keerit Tauh, Osama Ben Hameid, Richard Saczkowski, Alison E. Fox-Robichaud, Antoine Rochon, Denis Bouchard, Lebon Jean-Sébastien, Louis Perrault, Michel Pellerin, Philippe Demers, Pierre-Emmanuel Noly, Sebastian Andrés Parisi, Yoan Lamarche, Petr Kacer, Vladimir Buzalka, Dominik Petrovič, Filip Glac, Štefan Michut, Chris White, Craig D. Brown, Ivan Zalentsov, Jf Legare, Boris Akselrod, Andrey Lysenko, Artem Gubko, Denis Guskov, Ekaterina Tereshchenko, Evgeny Evseev, Olga Lipatova, Pavel Lednev, Emily Dai, Eric Deng, Gianluca Rigitano, Ingrid Copland, Jessica Vincent, Kumar Balasubramanian, Louay Habbab, Martin Renters, Nikki Pinder, Rutaba Khatun, Sarah Apolcer, Tahsin Ferdous, Yongning Ou, André Lamy, Emilie P. Belley-Côté, Fei Yuan, Jessica Spence, Michael H. McGillion, Pj Devereaux, Richard P. Whitlock, Salim Yusuf, Shrikant I. Bangdiwala, Joel Parlow, Rene Allard, Yiwei Xu, Yun Liu, Yunpeng Zhu, Anastasia V. Shudra, Artem V. Tolstykh, Dmitry V. Shmatov, Elizaveta A. Leonova, Nikita S. Popkov, Oleg B. Povodish, Polina N. Turina, Sergey Efremov, David Kent, Marnie Boyle, Michael Yamashita, Mullein Thorleifson, Nitin Ghorpade, Stephen Fremes, Ashvin K. Nair, Chew Yin Wang, Mohd Fitry Zainal Abidin, Noorjahan H. Md Hashim, Shahrul A. Hashim, Sivakumar Krishnasamy, Bernard McDonald, Dean Fergusson, Fraser Rubens, Dave Nagpal

Affiliations

¹ Population Health Research Institute, Hamilton, ON, Canada (A.L., E.P.B-C., R.P.W., I.C., J.V., R.K., K.B., S.I.B., M.H.M., J.S., S.Y., P.J.D.).
² Surgery (A.L., R.P.W.), McMaster University, Hamilton, ON, Canada.
³ E. Meshalkin National Medical Research Center, Novosibirsk, Russia (D.A.S.).
⁴ Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Canada (F.J.).
⁵ Kelowna General Hospital, BC, Canada (A.P.).
⁶ Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), QC, Canada (N.N.).
⁷ Saint Petersburg State University Hospital, Russia (S.E.).
⁸ Montreal Heart Institute, University of Montréal, QC, Canada (P.D.).
⁹ Petrovsky National Centre of Surgery, Moscow, Russia (B.A.).
¹⁰ Department of Anesthesiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia (C.Y.W.).
¹¹ Division of Cardiac Surgery, University Hospitals Harrington Heart and Vascular Institute, Cleveland, OH (R.C.A.).
¹² Department of Surgery, Case Western Reserve University, Cleveland, OH (R.C.A.).
¹³ Department of Cardiac Surgery, Hospital Agel Trinec-Podlesi, Trinec, Czech Republic (P.B.).
¹⁴ Auckland City Hospital, New Zealand (S.P.M.).
¹⁵ New Brunswick Heart Centre, Saint John, Canada (C.D.B.).
¹⁶ Centre Intégré Universitaire de Santé et de Services Sociaux du Nord-de-l'Île-de-Montréal, Hôpital du Sacré-Coeur de Montréal, QC, Canada (H.J.).
¹⁷ Rujin Hospital, Shanghai, China (Q.Z.).
¹⁸ Shanghai Jiao Tong University School of Medicine, China (Q.Z.).
¹⁹ Beijing Anzhen Hospital, China (H.Z.).
²⁰ Medicine (E.P.B-C., A.E.F-B., S.Y., P.J.D.), McMaster University, Hamilton, ON, Canada.
²¹ Hamilton Health Sciences, Hamilton General Hospital, Ontario, Canada (A.B.).
²² Departments of Health Research Methods, Evidence, and Impact (S.I.B., J.S., P.J.D.), McMaster University, Hamilton, ON, Canada.
²³ School of Nursing (M.H.M.), McMaster University, Hamilton, ON, Canada.
²⁴ Thrombosis and Atherosclerosis Research Institute (A.E.F-B.), McMaster University, Hamilton, ON, Canada.
²⁵ Anesthesia (J.S.), McMaster University, Hamilton, ON, Canada.

PMID: 38587333
DOI: 10.1161/CIRCULATIONAHA.124.069606

Abstract

Background: Although intravenous tranexamic acid is used in cardiac surgery to reduce bleeding and transfusion, topical tranexamic acid results in lower plasma concentrations compared with intravenous tranexamic acid, which may lower the risk of seizures. We aimed to determine whether topical tranexamic acid reduces the risk of in-hospital seizure without increasing the risk of transfusion among cardiac surgery patients.

Methods: We conducted a multicenter, double dummy, blinded, randomized controlled trial of patients recruited by convenience sampling in academic hospitals undergoing cardiac surgery with cardiopulmonary bypass. Between September 17, 2019, and November 28, 2023, a total of 3242 patients from 16 hospitals in 6 countries were randomly assigned (1:1 ratio) to receive either intravenous tranexamic acid (control) through surgery or topical tranexamic acid (treatment) at the end of surgery. The primary outcome was seizure, and the secondary outcome was red blood cell transfusion. After the last planned interim analysis, when 75% of anticipated participants had completed follow up, the data and safety monitoring board recommended to terminate the trial, and upon unblinding, the operations committee stopped the trial for safety.

Results: Among 3242 randomized patients (mean age, 66.0 years; 77.7% male), in-hospital seizure occurred in 4 of 1624 patients (0.2%) in the topical group, and 11 of 1628 patients (0.7%) in the intravenous group (absolute risk difference, -0.5% [95% CI, -0.9 to 0.03]; P=0.07). Red blood cell transfusion occurred in 570 patients (35.1%) in the topical group and in 433 (26.8%) in the intravenous group (absolute risk difference, 8.3% [95% CI, 5.2-11.5]; P=0.007). The absolute risk difference in transfusion of ≥4 units of red blood cells in the topical group compared with the intravenous group was 8.2% (95% CI, 3.4-12.9).

Conclusions: Among patients undergoing cardiac surgery, topical administration of tranexamic acid resulted in an 8.3% absolute increase in transfusion without reducing the incidence of seizure, compared with intravenous tranexamic acid.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03954314.

Keywords: administration, intravenous; administration, topical; blood transfusion; seizures; thoracic surgery; tranexamic acid.

PubMed Disclaimer

Conflict of interest statement

Dr Devereaux is employed as a professor at McMaster University. Dr Spence is employed as an anesthesiologist and intensivist at Hamilton Health Sciences and reports consultant fees from AOP Pharmaceuticals and PhaseBio outside the submitted work. Dr Whitlock reports grants from Abbott Canada during the conduct of the study and consultant fees from AtriCure Inc and Cytosorbents outside the submitted work. Dr Belley-Côté reports grants from Abbott Laboratories, Bayer, Bristol-Myers Squibb, Pfizer, and Roche Diagnostics Corporation during the conduct of the study and consultant fees from Trimedic Therapeutics outside the submitted work. Dr Arora reports other funding from Bioporto, Edwards Lifesciences, HLS Therapeutics Inc, and Renibus Therapeutics Inc outside the submitted work. The other authors report no conflicts.

Comment in

Bleeding After Cardiovascular Surgery: A Continuing Problem.
Sellke FW. Sellke FW. Circulation. 2024 Oct 22;150(17):1324-1326. doi: 10.1161/CIRCULATIONAHA.124.071147. Epub 2024 Oct 21. Circulation. 2024. PMID: 39432577 No abstract available.

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Topical Versus Intravenous Tranexamic Acid in Patients Undergoing Cardiac Surgery: The DEPOSITION Randomized Controlled Trial

Collaborators

Affiliations

Topical Versus Intravenous Tranexamic Acid in Patients Undergoing Cardiac Surgery: The DEPOSITION Randomized Controlled Trial

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Comment in

References

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MeSH terms

Substances

Associated data

LinkOut - more resources

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Medical