BACKGROUND: The prophylactic administration of tranexamic acid reduces blood loss during procedures at high risk of perioperative bleeding. Several studies in cardiac surgery and orthopedics confirmed this finding. The aim of this prospective, double-blind, randomized study is to evaluate the effect of tranexamic acid on peri-and postoperative blood loss and on the incidence and severity of complications. METHODS/DESIGN: Based on the results of our pilot study, we decided to conduct this prospective, double-blind, randomized trial to confirm the preliminary data. The primary endpoint is to analyze the effect of tranexamic acid on perioperative and postoperative blood loss (decrease in hemoglobin levels) in robotic-assisted radical prostatectomy. The additional endpoint is to analyze the effect of tranexamic acid on postoperative complications and confirm the safety of tranexamic acid in robotic-assisted radical prostatectomy. DISCUSSION: No study to date has tested the prophylactic administration of tranexamic acid at the beginning of robotic-assisted radical prostatectomy. This study is designed to answer the question of whether the administration of tranexamic acid might lower the blood loss after the procedure or increase the rate and severity of complications. TRIAL REGISTRATION: ClinicalTrials.gov NCT04319614. Registered on 25 March 2020.

Department of Surgery Charles University Faculty of Medicine in Hradec Králové Šimkova 870 500 03 Hradec Kralove Czech Republic

Department of Urology Charles University Faculty of Medicine in Hradec Králové Šimkova 870 500 03 Hradec Kralove Czech Republic

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Heidenreich A, Bastian P, Bellmunt J, Bolla M, Joniau S, van der Kwast T, et al. EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent—update 2013. Eur Urol. 2014;65(1):124–137. doi: 10.1016/j.eururo.2013.09.046. PubMed DOI

Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch M, De Santis M, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol. 2017;71(4):618–629. doi: 10.1016/j.eururo.2016.08.003. PubMed DOI

Nilsson S, Norlén B, Widmark A. A systematic overview of radiation therapy effects in prostate cancer. Acta Oncol. 2009;43(4):316–381. doi: 10.1080/02841860410030661. PubMed DOI

Barry M, Gallagher P, Skinner J, Fowler F. Adverse effects of robotic-assisted laparoscopic versus open retropubic radical prostatectomy among a nationwide random sample of medicare-age men. J Clin Oncol. 2012;30(5):513–518. doi: 10.1200/JCO.2011.36.8621. PubMed DOI PMC

Gandaglia G, Sammon J, Chang S, Choueiri T, Hu J, Karakiewicz P, et al. Comparative effectiveness of robot-assisted and open radical prostatectomy in the postdissemination era. J Clin Oncol. 2014;32(14):1419–1426. doi: 10.1200/JCO.2013.53.5096. PubMed DOI

Kasabwala K, Patel N, Hu J. Review of optimal techniques for robotic-assisted radical prostatectomy. Curr Opin Urol. 2018;28(2):102–107. doi: 10.1097/MOU.0000000000000473. PubMed DOI

Montorsi F, Wilson T, Rosen R, Ahlering T, Artibani W, Carroll P, et al. Best practices in robot-assisted radical prostatectomy: recommendations of the Pasadena consensus panel. Eur Urol. 2012;62(3):368–381. doi: 10.1016/j.eururo.2012.05.057. PubMed DOI

Sammon J, Karakiewicz P, Sun M, Sukumar S, Ravi P, Ghani K, et al. Robot-assisted versus open radical prostatectomy: the differential effect of regionalization, procedure volume and operative approach. J Urol. 2013;189(4):1289–1294. doi: 10.1016/j.juro.2012.10.028. PubMed DOI

Rothermel L, Lipman J. Estimation of blood loss is inaccurate and unreliable. Surgery. 2016;160(4):946–953. doi: 10.1016/j.surg.2016.06.006. PubMed DOI

Poletajew S, Antoniewicz A. Urological oncology. Blood loss during laparoscopic radical prostatectomy – is it significant or not? Central Eur J Urol. 2012;65:11–13. doi: 10.5173/ceju.2012.01.art3. PubMed DOI PMC

Lee S, Seo H, Kim H, Lim S, Yoon S, Kim H, et al. Effect of intraoperative red blood cell transfusion on postoperative complications after open radical cystectomy: old versus fresh stored blood. Clin Genitourin Cancer. 2015;13(6):581–587. doi: 10.1016/j.clgc.2015.06.002. PubMed DOI

Sampaio A, Guimarães G, Medeiros G, Damasceno G, Silva R, Nunes R, et al. Eficácia e segurança de antifibrinolíticos em cirurgia oncológica: uma revisão sistemática e metanálise. Braz J Anesthesiol. 2019;69(5):484–492. doi: 10.1016/j.bjan.2019.06.005. PubMed DOI PMC

Henry D, Carles P, Moxey A, O’Connell D, Stokes B, Fergusson D, et al. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2011;2011(3):CD001886. PubMed PMC

Levi M, Levy J, Andersen H, Truloff D. Safety of recombinant activated factor VII in randomized clinical trials. N Engl J Med. 2010;363(19):1791–1800. doi: 10.1056/NEJMoa1006221. PubMed DOI

Fergusson D, Hébert P, Mazer C, Fremes S, MacAdams C, Murkin J, et al. A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. N Engl J Med. 2008;358(22):2319–2331. doi: 10.1056/NEJMoa0802395. PubMed DOI

Dunn C, Goa K. Tranexamic acid. Drugs. 1999;57(6):1005–1032. doi: 10.2165/00003495-199957060-00017. PubMed DOI

Erstad B. Systemic hemostatic medications for reducing surgical blood loss. Ann Pharmacother. 2001;35(7-8):925–934. doi: 10.1345/aph.10337. PubMed DOI

McCormack P. Tranexamic acid. Drugs. 2012;72(5):585–617. doi: 10.2165/11209070-000000000-00000. PubMed DOI

Benoni G, Lethagen S, Nilsson P, Fredin H. Tranexamic acid, given at the end of the operation, does not reduce postoperative blood loss in hip arthroplasty. Acta Orthop Scand. 2009;71(3):250–254. doi: 10.1080/000164700317411834. PubMed DOI

Nielsen J, Gram J, Fabrin K, Holm-Nielsen A, Jespersen J. Lack of correlation between blood fibrinolysis and the immediate or post-operative blood loss in transurethral resection of the prostate. BJU Int. 1997;80(1):105–110. doi: 10.1046/j.1464-410X.1997.00251.x. PubMed DOI

Sharifi R, Lee M, Ray P, Millner S, Dupont P. Safety and efficacy of intravesical aminocaproic acid for bleeding after transurethral resection of prostate. Urology. 1986;27(3):214–219. doi: 10.1016/0090-4295(86)90277-3. PubMed DOI

Jendoubi A, Malouch A, Bouzouita A, Riahi Y, Necib H, Ghedira S, et al. Intérêt de l’acide tranexamique dans les résections endoscopiques urologiques : étude prospective randomisée. Prog Urol. 2017;27(16):1036–1042. doi: 10.1016/j.purol.2017.09.008. PubMed DOI

Rannikko A, Pétas A, Taari K. Tranexamic acid in control of primary hemorrhage during transurethral prostatectomy. Urology. 2004;64(5):955–958. doi: 10.1016/j.urology.2004.07.008. PubMed DOI

Kumsar Ş, Dirim A, Toksöz S, Sağlam H, Adsan Ö. BPH tranexamic acid decreases blood loss during transurethral resection of the prostate (TUR-P) Central Eur J Urol. 2011;64:156–158. doi: 10.5173/ceju.2011.03.art13. PubMed DOI PMC

Crescenti A, Borghi G, Bignami E, Bertarelli G, Landoni G, Casiraghi G, et al. Intraoperative use of tranexamic acid to reduce transfusion rate in patients undergoing radical retropubic prostatectomy: double blind, randomised, placebo controlled trial. BMJ. 2011;343(oct19 3):d5701. doi: 10.1136/bmj.d5701. PubMed DOI PMC

Zaid H, Yang D, Tollefson M, Frank I, Winters J, Thapa P, et al. Efficacy and safety of intraoperative tranexamic acid infusion for reducing blood transfusion during open radical cystectomy. Urology. 2016;92:57–62. doi: 10.1016/j.urology.2016.02.044. PubMed DOI

Montroy J, Fergusson N, Hutton B, Lavallée L, Morash C, Cagiannos I, et al. The safety and efficacy of lysine analogues in cancer patients: a systematic review and meta-analysis. Transfus Med Rev. 2017;31(3):141–148. doi: 10.1016/j.tmrv.2017.03.002. PubMed DOI

Longo M, Cavalheiro B, de Oliveira Filho G. Systematic review and meta-analyses of tranexamic acid use for bleeding reduction in prostate surgery. J Clin Anesth. 2018;48:32–38. doi: 10.1016/j.jclinane.2018.04.014. PubMed DOI

Balík M, Košina J, Hušek P, Broďák M, Čečka F. Safety and efficacy of using tranexamic acid at the beginning of robotic-assisted radical prostatectomy in a double-blind prospective randomized pilot study. Acta Med Austriaca. 2020;2020(64):176–182. PubMed

Martini A, Tewari A. Anatomic robotic prostatectomy: current best practice. Ther Adv Urol. 2019;11 [cited 2022-01-04]. Available from: http://journals.sagepub.com/doi/10.1177/1756287218813789. PubMed DOI PMC

Pacovský J, Hušek P, Balík M, Louda M, Košina J, Navrátil P. Biochemic evidence of the presence of urine in a drain following surgery. Rozhl Chir. 2011;2011(90):478–481. PubMed

Dias Neto J, Dall’oglio M, Colombo J, Jr, Coelho R, Nahas W. The influence of previous robotic experience in the initial learning curve of laparoscopic radical prostatectomy. Int Braz J Urol. 2017;43(5):871–879. doi: 10.1590/s1677-5538.ibju.2016.0526. PubMed DOI PMC

Dindo D, Demartines N, Clavien P. Classification of surgical complications. Ann Surg. 2004;240(2):205–213. doi: 10.1097/01.sla.0000133083.54934.ae. PubMed DOI PMC

Schulz K, Altman D, Moher D. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340(mar23 1):c332. doi: 10.1136/bmj.c332. PubMed DOI PMC

Chan A, Tetzlaff J, Gotzsche P, Altman D, Mann H, Berlin J, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013;346(jan08 15):e7586. doi: 10.1136/bmj.e7586. PubMed DOI PMC

Chesnut G, Benfante N, Barham D, Dean L, Tin A, Sjoberg D, et al. Routine postoperative hemoglobin assessment poorly predicts transfusion requirement among patients undergoing minimally invasive radical prostatectomy. Urol Pract. 2020;7(4):299–304. doi: 10.1097/UPJ.0000000000000108. PubMed DOI PMC

Dean L, Tin A, Chesnut G, Assel M, LaDuke E, Fromkin J, et al. Contemporary management of hemorrhage after minimally invasive radical prostatectomy. Urology. 2019;130:120–125. doi: 10.1016/j.urology.2019.04.021. PubMed DOI PMC

Elizalde J, Clemente J, Marin J, Panes J, Aragon B, Mas A, et al. Early changes in hemoglobin and hematocrit levels after packed red cell transfusion in patients with acute anemia. Transfusion. 1997;37(6):573–576. doi: 10.1046/j.1537-2995.1997.37697335150.x. PubMed DOI

Kashefi P, Rahmani A, Khalifesoltani M. Changes in the hemoglobin level after one unit of packed red blood cell transfusion in intensive care unit patients. J Res Med Sci. 2018;23(1) [cited 2022-01-04]. Available from: http://www.jmsjournal.net/text.asp?2018/23/1/85/242089. PubMed PMC

Meunier A, Petersson A, Good L, Berlin G. Validation of a haemoglobin dilution method for estimation of blood loss. Vox Sang. 2008;95(2):120–124. doi: 10.1111/j.1423-0410.2008.01071.x. PubMed DOI

Chan R, Barocas D, Chang S, Herrell S, Clark P, Baumgartner R, et al. Effect of a large prostate gland on open and robotically assisted laparoscopic radical prostatectomy. BJU Int. 2008;101(9):1140–1144. doi: 10.1111/j.1464-410X.2007.07428.x. PubMed DOI

Kordan Y, Barocas D, Altamar H, Clark P, Chang S, Davis R, et al. Comparison of transfusion requirements between open and robotic-assisted laparoscopic radical prostatectomy. BJU Int. 2010;106(7):1036–1040. doi: 10.1111/j.1464-410X.2010.09233.x. PubMed DOI

Goodnough L, Brecher M, Kanter M, AuBuchon J. Transfusion medicine—blood transfusion. N Engl J Med. 1999;340(6):438–447. doi: 10.1056/NEJM199902113400606. PubMed DOI

Linder B, Frank I, Cheville J, Tollefson M, Thompson R, Tarrell R, et al. The impact of perioperative blood transfusion on cancer recurrence and survival following radical cystectomy. Eur Urol. 2013;63(5):839–845. doi: 10.1016/j.eururo.2013.01.004. PubMed DOI

Wang Y, Jiang B, Yin F, Shi H, Xu X, Zheng S, et al. Perioperative blood transfusion promotes worse outcomes of bladder cancer after radical cystectomy: a systematic review and meta-analysis. PLoS One. 2015;10(6) [cited 2022-01-04]. Available from: https://dx.plos.org/10.1371/journal.pone.0130122. PubMed DOI PMC

Tikkinen K, Craigie S, Agarwal A, Violette P, Novara G, Cartwright R, et al. Procedure-specific risks of thrombosis and bleeding in urological cancer surgery: systematic review and meta-analysis. Eur Urol. 2018;73(2):242–251. doi: 10.1016/j.eururo.2017.03.008. PubMed DOI

Wolfenden L, Foy R, Presseau J, Grimshaw J, Ivers N, Powell B, et al. Designing and undertaking randomised implementation trials: guide for researchers. BMJ. [cited 2022-01-05];. Available from: https://www.bmj.com/lookup/doi/10.1136/bmj.m3721. PubMed DOI PMC

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NCT04319614