Aggressive fluid hydration plus non-steroidal anti-inflammatory drugs versus non-steroidal anti-inflammatory drugs alone for post-endoscopic retrograde cholangiopancreatography pancreatitis (FLUYT): a multicentre, open-label, randomised, controlled trial

Christina J. Sperna Weiland; Xavier J.N.M. Smeets; the Dutch Pancreatitis Study Group; Wietske Kievit; Robert C. Verdonk; Alexander C. Poen; Abha Bhalla; Niels G. Venneman; Ben J.M. Witteman; David W. da Costa; Brechje C. van Eijck; Matthijs P. Schwartz; Tessa E.H. Römkens; Jan Maarten Vrolijk; Muhammed Hadithi; Annet M.C.J. Voorburg; Lubbertus C. Baak; Willem J. Thijs; Roy L. van Wanrooij; Adriaan C.I.T.L. Tan; Tom C.J. Seerden; Yolande C.A. Keulemans; Thomas R. de Wijkerslooth; Wim van de Vrie; Peter van der Schaar; Sven M. van Dijk; Nora D.L. Hallensleben; Ruud L. Sperna Weiland; Hester C. Timmerhuis; Devica S. Umans; Jeanin E. van Hooft; Harry van Goor; Hjalmar C. van Santvoort; Marc G. Besselink; Marco J. Bruno; Paul Fockens; Joost P.H. Drenth; Erwin J.M. van Geenen

doi:10.1016/S2468-1253(21)00057-1

Aggressive fluid hydration plus non-steroidal anti-inflammatory drugs versus non-steroidal anti-inflammatory drugs alone for post-endoscopic retrograde cholangiopancreatography pancreatitis (FLUYT): a multicentre, open-label, randomised, controlled trial

Christina J. Sperna Weiland, Xavier J.N.M. Smeets, the Dutch Pancreatitis Study Group, Wietske Kievit, Robert C. Verdonk, Alexander C. Poen, Abha Bhalla, Niels G. Venneman, Ben J.M. Witteman, David W. da Costa, Brechje C. van Eijck, Matthijs P. Schwartz, Tessa E.H. Römkens, Jan Maarten Vrolijk, Muhammed Hadithi, Annet M.C.J. Voorburg, Lubbertus C. Baak, Willem J. Thijs, Roy L. van Wanrooij, Adriaan C.I.T.L. TanTom C.J. Seerden, Yolande C.A. Keulemans, Thomas R. de Wijkerslooth, Wim van de Vrie, Peter van der Schaar, Sven M. van Dijk, Nora D.L. Hallensleben, Ruud L. Sperna Weiland, Hester C. Timmerhuis, Devica S. Umans, Jeanin E. van Hooft, Harry van Goor, Hjalmar C. van Santvoort, Marc G. Besselink, Marco J. Bruno, Paul Fockens, Joost P.H. Drenth, Erwin J.M. van Geenen^*

^*Corresponding author for this work

Gastroenterology & Hepatology

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Background: Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Prophylactic rectal administration of non-steroidal anti-inflammatory drugs (NSAIDs) is considered as standard of care to reduce the risk of post-ERCP pancreatitis. It has been suggested that aggressive hydration might further reduce this risk. Guidelines already recommend aggressive hydration in patients who are unable to receive rectal NSAIDs, although it is laborious and time consuming. We aimed to evaluate the added value of aggressive hydration in patients receiving prophylactic rectal NSAIDs. Methods: FLUYT, a multicentre, open-label, randomised, controlled trial done across 22 Dutch hospitals, included patients aged between 18 and 85 years with moderate to high risk of post-ERCP pancreatitis. Patients were randomly assigned (1:1) by a web-based module with varying block sizes to a combination of aggressive hydration and rectal NSAIDs (100 mg diclofenac or indomethacin; aggressive hydration group) or rectal NSAIDs (100 mg diclofenac or indomethacin) alone (control group). Randomisation was stratified according to treatment centre. Aggressive hydration comprised 20 mL/kg intravenous Ringer's lactate solution within 60 min from the start of ERCP, followed by 3 mL/kg per h for 8 h. The control group received normal intravenous saline with a maximum of 1·5 mL/kg per h and 3 L per 24 h. The primary endpoint was post-ERCP pancreatitis and was analysed on a modified intention-to-treat basis (including all patients who underwent randomisation and an ERCP and for whom data regarding the primary outcome were available). The trial is registered with the ISRCTN registry, ISRCTN13659155. Findings: Between June 5, 2015, and June 6, 2019, 826 patients were randomly assigned, of whom 388 in the aggressive hydration group and 425 in the control group were included in the modified intention-to-treat analysis. Post-ERCP pancreatitis occurred in 30 (8%) patients in the aggressive hydration group and in 39 (9%) patients in the control group (relative risk 0·84, 95% CI 0·53–1·33, p=0·53). There were no differences in serious adverse events, including hydration-related complications (relative risk 0·99, 95% CI 0·59–1·64; p=1·00), ERCP-related complications (0·90, 0·62–1·31; p=0·62), intensive care unit admission (0·37, 0·07–1·80; p=0·22), and 30-day mortality (0·95, 0·50–1·83; p=1·00). Interpretation: Aggressive periprocedural hydration did not reduce the incidence of post-ERCP pancreatitis in patients with moderate to high risk of developing this complication who routinely received prophylactic rectal NSAIDs. Therefore, the burden of laborious and time-consuming aggressive periprocedural hydration to further reduce the risk of post-ERCP pancreatitis is not justified. Funding: Netherlands Organisation for Health Research and Development and Radboud University Medical Center.

Original language	English
Pages (from-to)	350-358
Number of pages	9
Journal	The Lancet Gastroenterology and Hepatology
Volume	6
Issue number	5
Early online date	12 Apr 2021
DOIs	https://doi.org/10.1016/S2468-1253(21)00057-1
Publication status	Published - May 2021

Bibliographical note

Funding Information:
The study was funded by the Netherlands Organisation for Health Research and Development ( grant number 837001506 ) and the Radboud University Medical Center. We thank members of the data safety monitoring board (Ruud Loffeld [chair; Department of Gastroenterology and Hepatology, Zaans Medical Centre, Zaandam, Netherlands], Tom Nijenhuis [Department of Nephrology, Radboud University Medical Center, Nijmegen, Netherlands], David M Burger [Department of Pharmacy, Radboud University Medical Center, Nijmegen, Netherlands], and Michiel Vaneker [Department of Anesthesiology, Radboud University Medical Center, Nijmegen, Netherlands]) and the independent statistician for the interim analysis (Joanna IntHout at the Department for Health Evidence, Radboud University Medical Center, Nijmegen, Netherlands) for their services.

Funding Information:
The study was funded by the Netherlands Organisation for Health Research and Development (grant number 837001506) and the Radboud University Medical Center. We thank members of the data safety monitoring board (Ruud Loffeld [chair; Department of Gastroenterology and Hepatology, Zaans Medical Centre, Zaandam, Netherlands], Tom Nijenhuis [Department of Nephrology, Radboud University Medical Center, Nijmegen, Netherlands], David M Burger [Department of Pharmacy, Radboud University Medical Center, Nijmegen, Netherlands], and Michiel Vaneker [Department of Anesthesiology, Radboud University Medical Center, Nijmegen, Netherlands]) and the independent statistician for the interim analysis (Joanna IntHout at the Department for Health Evidence, Radboud University Medical Center, Nijmegen, Netherlands) for their services.

Funding Information:
EJMvG reports grants from Mylan and Olympus and personal fees from MTW-Endoskopie, outside the submitted work. JPHD reports grants from Gilead, outside the submitted work. PF reports personal fees from Olympus, Cook Medical, and Ethicon Endosurgery, outside the submitted work. MJB reports personal fees from Boston Scientific, grants and personal fees from Cook Medical, and grants from Pentax Medical, 3M, InterScope, and Mylan, outside the submitted work. JEvH reports grants and personal fees from Cook Medical and personal fees from Boston Scientific and Medtronics, outside the submitted work. All other authors declare no competing interests.

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Sperna Weiland, C. J., Smeets, X. J. N. M., the Dutch Pancreatitis Study Group, Kievit, W., Verdonk, R. C., Poen, A. C., Bhalla, A., Venneman, N. G., Witteman, B. J. M., da Costa, D. W., van Eijck, B. C., Schwartz, M. P., Römkens, T. E. H., Vrolijk, J. M., Hadithi, M., Voorburg, A. M. C. J., Baak, L. C., Thijs, W. J., van Wanrooij, R. L., ... van Geenen, E. J. M. (2021). Aggressive fluid hydration plus non-steroidal anti-inflammatory drugs versus non-steroidal anti-inflammatory drugs alone for post-endoscopic retrograde cholangiopancreatography pancreatitis (FLUYT): a multicentre, open-label, randomised, controlled trial. The Lancet Gastroenterology and Hepatology, 6(5), 350-358. https://doi.org/10.1016/S2468-1253(21)00057-1

Sperna Weiland, Christina J. ; Smeets, Xavier J.N.M. ; the Dutch Pancreatitis Study Group et al. / Aggressive fluid hydration plus non-steroidal anti-inflammatory drugs versus non-steroidal anti-inflammatory drugs alone for post-endoscopic retrograde cholangiopancreatography pancreatitis (FLUYT) : a multicentre, open-label, randomised, controlled trial. In: The Lancet Gastroenterology and Hepatology. 2021 ; Vol. 6, No. 5. pp. 350-358.

@article{4441787b359c4f24ba839204ef2f0ac6,

title = "Aggressive fluid hydration plus non-steroidal anti-inflammatory drugs versus non-steroidal anti-inflammatory drugs alone for post-endoscopic retrograde cholangiopancreatography pancreatitis (FLUYT): a multicentre, open-label, randomised, controlled trial",

abstract = "Background: Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Prophylactic rectal administration of non-steroidal anti-inflammatory drugs (NSAIDs) is considered as standard of care to reduce the risk of post-ERCP pancreatitis. It has been suggested that aggressive hydration might further reduce this risk. Guidelines already recommend aggressive hydration in patients who are unable to receive rectal NSAIDs, although it is laborious and time consuming. We aimed to evaluate the added value of aggressive hydration in patients receiving prophylactic rectal NSAIDs. Methods: FLUYT, a multicentre, open-label, randomised, controlled trial done across 22 Dutch hospitals, included patients aged between 18 and 85 years with moderate to high risk of post-ERCP pancreatitis. Patients were randomly assigned (1:1) by a web-based module with varying block sizes to a combination of aggressive hydration and rectal NSAIDs (100 mg diclofenac or indomethacin; aggressive hydration group) or rectal NSAIDs (100 mg diclofenac or indomethacin) alone (control group). Randomisation was stratified according to treatment centre. Aggressive hydration comprised 20 mL/kg intravenous Ringer's lactate solution within 60 min from the start of ERCP, followed by 3 mL/kg per h for 8 h. The control group received normal intravenous saline with a maximum of 1·5 mL/kg per h and 3 L per 24 h. The primary endpoint was post-ERCP pancreatitis and was analysed on a modified intention-to-treat basis (including all patients who underwent randomisation and an ERCP and for whom data regarding the primary outcome were available). The trial is registered with the ISRCTN registry, ISRCTN13659155. Findings: Between June 5, 2015, and June 6, 2019, 826 patients were randomly assigned, of whom 388 in the aggressive hydration group and 425 in the control group were included in the modified intention-to-treat analysis. Post-ERCP pancreatitis occurred in 30 (8%) patients in the aggressive hydration group and in 39 (9%) patients in the control group (relative risk 0·84, 95% CI 0·53–1·33, p=0·53). There were no differences in serious adverse events, including hydration-related complications (relative risk 0·99, 95% CI 0·59–1·64; p=1·00), ERCP-related complications (0·90, 0·62–1·31; p=0·62), intensive care unit admission (0·37, 0·07–1·80; p=0·22), and 30-day mortality (0·95, 0·50–1·83; p=1·00). Interpretation: Aggressive periprocedural hydration did not reduce the incidence of post-ERCP pancreatitis in patients with moderate to high risk of developing this complication who routinely received prophylactic rectal NSAIDs. Therefore, the burden of laborious and time-consuming aggressive periprocedural hydration to further reduce the risk of post-ERCP pancreatitis is not justified. Funding: Netherlands Organisation for Health Research and Development and Radboud University Medical Center.",

author = "{Sperna Weiland}, {Christina J.} and Smeets, {Xavier J.N.M.} and {the Dutch Pancreatitis Study Group} and Wietske Kievit and Verdonk, {Robert C.} and Poen, {Alexander C.} and Abha Bhalla and Venneman, {Niels G.} and Witteman, {Ben J.M.} and {da Costa}, {David W.} and {van Eijck}, {Brechje C.} and Schwartz, {Matthijs P.} and R{\"o}mkens, {Tessa E.H.} and Vrolijk, {Jan Maarten} and Muhammed Hadithi and Voorburg, {Annet M.C.J.} and Baak, {Lubbertus C.} and Thijs, {Willem J.} and {van Wanrooij}, {Roy L.} and Tan, {Adriaan C.I.T.L.} and Seerden, {Tom C.J.} and Keulemans, {Yolande C.A.} and {de Wijkerslooth}, {Thomas R.} and {van de Vrie}, Wim and {van der Schaar}, Peter and {van Dijk}, {Sven M.} and Hallensleben, {Nora D.L.} and {Sperna Weiland}, {Ruud L.} and Timmerhuis, {Hester C.} and Umans, {Devica S.} and {van Hooft}, {Jeanin E.} and {van Goor}, Harry and {van Santvoort}, {Hjalmar C.} and Besselink, {Marc G.} and Bruno, {Marco J.} and Paul Fockens and Drenth, {Joost P.H.} and {van Geenen}, {Erwin J.M.}",

note = "Funding Information: The study was funded by the Netherlands Organisation for Health Research and Development ( grant number 837001506 ) and the Radboud University Medical Center. We thank members of the data safety monitoring board (Ruud Loffeld [chair; Department of Gastroenterology and Hepatology, Zaans Medical Centre, Zaandam, Netherlands], Tom Nijenhuis [Department of Nephrology, Radboud University Medical Center, Nijmegen, Netherlands], David M Burger [Department of Pharmacy, Radboud University Medical Center, Nijmegen, Netherlands], and Michiel Vaneker [Department of Anesthesiology, Radboud University Medical Center, Nijmegen, Netherlands]) and the independent statistician for the interim analysis (Joanna IntHout at the Department for Health Evidence, Radboud University Medical Center, Nijmegen, Netherlands) for their services. Funding Information: The study was funded by the Netherlands Organisation for Health Research and Development (grant number 837001506) and the Radboud University Medical Center. We thank members of the data safety monitoring board (Ruud Loffeld [chair; Department of Gastroenterology and Hepatology, Zaans Medical Centre, Zaandam, Netherlands], Tom Nijenhuis [Department of Nephrology, Radboud University Medical Center, Nijmegen, Netherlands], David M Burger [Department of Pharmacy, Radboud University Medical Center, Nijmegen, Netherlands], and Michiel Vaneker [Department of Anesthesiology, Radboud University Medical Center, Nijmegen, Netherlands]) and the independent statistician for the interim analysis (Joanna IntHout at the Department for Health Evidence, Radboud University Medical Center, Nijmegen, Netherlands) for their services. Funding Information: EJMvG reports grants from Mylan and Olympus and personal fees from MTW-Endoskopie, outside the submitted work. JPHD reports grants from Gilead, outside the submitted work. PF reports personal fees from Olympus, Cook Medical, and Ethicon Endosurgery, outside the submitted work. MJB reports personal fees from Boston Scientific, grants and personal fees from Cook Medical, and grants from Pentax Medical, 3M, InterScope, and Mylan, outside the submitted work. JEvH reports grants and personal fees from Cook Medical and personal fees from Boston Scientific and Medtronics, outside the submitted work. All other authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 Elsevier Ltd",

year = "2021",

month = may,

doi = "10.1016/S2468-1253(21)00057-1",

language = "English",

volume = "6",

pages = "350--358",

journal = "The Lancet Gastroenterology and Hepatology",

issn = "2468-1253",

publisher = "Elsevier Ltd.",

number = "5",

}

Sperna Weiland, CJ, Smeets, XJNM, the Dutch Pancreatitis Study Group, Kievit, W, Verdonk, RC, Poen, AC, Bhalla, A, Venneman, NG, Witteman, BJM, da Costa, DW, van Eijck, BC, Schwartz, MP, Römkens, TEH, Vrolijk, JM, Hadithi, M, Voorburg, AMCJ, Baak, LC, Thijs, WJ, van Wanrooij, RL, Tan, ACITL, Seerden, TCJ, Keulemans, YCA, de Wijkerslooth, TR, van de Vrie, W, van der Schaar, P, van Dijk, SM, Hallensleben, NDL, Sperna Weiland, RL, Timmerhuis, HC, Umans, DS, van Hooft, JE, van Goor, H, van Santvoort, HC, Besselink, MG, Bruno, MJ, Fockens, P, Drenth, JPH & van Geenen, EJM 2021, 'Aggressive fluid hydration plus non-steroidal anti-inflammatory drugs versus non-steroidal anti-inflammatory drugs alone for post-endoscopic retrograde cholangiopancreatography pancreatitis (FLUYT): a multicentre, open-label, randomised, controlled trial', The Lancet Gastroenterology and Hepatology, vol. 6, no. 5, pp. 350-358. https://doi.org/10.1016/S2468-1253(21)00057-1

Aggressive fluid hydration plus non-steroidal anti-inflammatory drugs versus non-steroidal anti-inflammatory drugs alone for post-endoscopic retrograde cholangiopancreatography pancreatitis (FLUYT): a multicentre, open-label, randomised, controlled trial. / Sperna Weiland, Christina J.; Smeets, Xavier J.N.M.; the Dutch Pancreatitis Study Group et al.
In: The Lancet Gastroenterology and Hepatology, Vol. 6, No. 5, 05.2021, p. 350-358.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Aggressive fluid hydration plus non-steroidal anti-inflammatory drugs versus non-steroidal anti-inflammatory drugs alone for post-endoscopic retrograde cholangiopancreatography pancreatitis (FLUYT)

T2 - a multicentre, open-label, randomised, controlled trial

AU - Sperna Weiland, Christina J.

AU - Smeets, Xavier J.N.M.

AU - the Dutch Pancreatitis Study Group

AU - Kievit, Wietske

AU - Verdonk, Robert C.

AU - Poen, Alexander C.

AU - Bhalla, Abha

AU - Venneman, Niels G.

AU - Witteman, Ben J.M.

AU - da Costa, David W.

AU - van Eijck, Brechje C.

AU - Schwartz, Matthijs P.

AU - Römkens, Tessa E.H.

AU - Vrolijk, Jan Maarten

AU - Hadithi, Muhammed

AU - Voorburg, Annet M.C.J.

AU - Baak, Lubbertus C.

AU - Thijs, Willem J.

AU - van Wanrooij, Roy L.

AU - Tan, Adriaan C.I.T.L.

AU - Seerden, Tom C.J.

AU - Keulemans, Yolande C.A.

AU - de Wijkerslooth, Thomas R.

AU - van de Vrie, Wim

AU - van der Schaar, Peter

AU - van Dijk, Sven M.

AU - Hallensleben, Nora D.L.

AU - Sperna Weiland, Ruud L.

AU - Timmerhuis, Hester C.

AU - Umans, Devica S.

AU - van Hooft, Jeanin E.

AU - van Goor, Harry

AU - van Santvoort, Hjalmar C.

AU - Besselink, Marc G.

AU - Bruno, Marco J.

AU - Fockens, Paul

AU - Drenth, Joost P.H.

AU - van Geenen, Erwin J.M.

N1 - Funding Information: The study was funded by the Netherlands Organisation for Health Research and Development ( grant number 837001506 ) and the Radboud University Medical Center. We thank members of the data safety monitoring board (Ruud Loffeld [chair; Department of Gastroenterology and Hepatology, Zaans Medical Centre, Zaandam, Netherlands], Tom Nijenhuis [Department of Nephrology, Radboud University Medical Center, Nijmegen, Netherlands], David M Burger [Department of Pharmacy, Radboud University Medical Center, Nijmegen, Netherlands], and Michiel Vaneker [Department of Anesthesiology, Radboud University Medical Center, Nijmegen, Netherlands]) and the independent statistician for the interim analysis (Joanna IntHout at the Department for Health Evidence, Radboud University Medical Center, Nijmegen, Netherlands) for their services. Funding Information: The study was funded by the Netherlands Organisation for Health Research and Development (grant number 837001506) and the Radboud University Medical Center. We thank members of the data safety monitoring board (Ruud Loffeld [chair; Department of Gastroenterology and Hepatology, Zaans Medical Centre, Zaandam, Netherlands], Tom Nijenhuis [Department of Nephrology, Radboud University Medical Center, Nijmegen, Netherlands], David M Burger [Department of Pharmacy, Radboud University Medical Center, Nijmegen, Netherlands], and Michiel Vaneker [Department of Anesthesiology, Radboud University Medical Center, Nijmegen, Netherlands]) and the independent statistician for the interim analysis (Joanna IntHout at the Department for Health Evidence, Radboud University Medical Center, Nijmegen, Netherlands) for their services. Funding Information: EJMvG reports grants from Mylan and Olympus and personal fees from MTW-Endoskopie, outside the submitted work. JPHD reports grants from Gilead, outside the submitted work. PF reports personal fees from Olympus, Cook Medical, and Ethicon Endosurgery, outside the submitted work. MJB reports personal fees from Boston Scientific, grants and personal fees from Cook Medical, and grants from Pentax Medical, 3M, InterScope, and Mylan, outside the submitted work. JEvH reports grants and personal fees from Cook Medical and personal fees from Boston Scientific and Medtronics, outside the submitted work. All other authors declare no competing interests. Publisher Copyright: © 2021 Elsevier Ltd

PY - 2021/5

Y1 - 2021/5

N2 - Background: Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Prophylactic rectal administration of non-steroidal anti-inflammatory drugs (NSAIDs) is considered as standard of care to reduce the risk of post-ERCP pancreatitis. It has been suggested that aggressive hydration might further reduce this risk. Guidelines already recommend aggressive hydration in patients who are unable to receive rectal NSAIDs, although it is laborious and time consuming. We aimed to evaluate the added value of aggressive hydration in patients receiving prophylactic rectal NSAIDs. Methods: FLUYT, a multicentre, open-label, randomised, controlled trial done across 22 Dutch hospitals, included patients aged between 18 and 85 years with moderate to high risk of post-ERCP pancreatitis. Patients were randomly assigned (1:1) by a web-based module with varying block sizes to a combination of aggressive hydration and rectal NSAIDs (100 mg diclofenac or indomethacin; aggressive hydration group) or rectal NSAIDs (100 mg diclofenac or indomethacin) alone (control group). Randomisation was stratified according to treatment centre. Aggressive hydration comprised 20 mL/kg intravenous Ringer's lactate solution within 60 min from the start of ERCP, followed by 3 mL/kg per h for 8 h. The control group received normal intravenous saline with a maximum of 1·5 mL/kg per h and 3 L per 24 h. The primary endpoint was post-ERCP pancreatitis and was analysed on a modified intention-to-treat basis (including all patients who underwent randomisation and an ERCP and for whom data regarding the primary outcome were available). The trial is registered with the ISRCTN registry, ISRCTN13659155. Findings: Between June 5, 2015, and June 6, 2019, 826 patients were randomly assigned, of whom 388 in the aggressive hydration group and 425 in the control group were included in the modified intention-to-treat analysis. Post-ERCP pancreatitis occurred in 30 (8%) patients in the aggressive hydration group and in 39 (9%) patients in the control group (relative risk 0·84, 95% CI 0·53–1·33, p=0·53). There were no differences in serious adverse events, including hydration-related complications (relative risk 0·99, 95% CI 0·59–1·64; p=1·00), ERCP-related complications (0·90, 0·62–1·31; p=0·62), intensive care unit admission (0·37, 0·07–1·80; p=0·22), and 30-day mortality (0·95, 0·50–1·83; p=1·00). Interpretation: Aggressive periprocedural hydration did not reduce the incidence of post-ERCP pancreatitis in patients with moderate to high risk of developing this complication who routinely received prophylactic rectal NSAIDs. Therefore, the burden of laborious and time-consuming aggressive periprocedural hydration to further reduce the risk of post-ERCP pancreatitis is not justified. Funding: Netherlands Organisation for Health Research and Development and Radboud University Medical Center.

AB - Background: Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Prophylactic rectal administration of non-steroidal anti-inflammatory drugs (NSAIDs) is considered as standard of care to reduce the risk of post-ERCP pancreatitis. It has been suggested that aggressive hydration might further reduce this risk. Guidelines already recommend aggressive hydration in patients who are unable to receive rectal NSAIDs, although it is laborious and time consuming. We aimed to evaluate the added value of aggressive hydration in patients receiving prophylactic rectal NSAIDs. Methods: FLUYT, a multicentre, open-label, randomised, controlled trial done across 22 Dutch hospitals, included patients aged between 18 and 85 years with moderate to high risk of post-ERCP pancreatitis. Patients were randomly assigned (1:1) by a web-based module with varying block sizes to a combination of aggressive hydration and rectal NSAIDs (100 mg diclofenac or indomethacin; aggressive hydration group) or rectal NSAIDs (100 mg diclofenac or indomethacin) alone (control group). Randomisation was stratified according to treatment centre. Aggressive hydration comprised 20 mL/kg intravenous Ringer's lactate solution within 60 min from the start of ERCP, followed by 3 mL/kg per h for 8 h. The control group received normal intravenous saline with a maximum of 1·5 mL/kg per h and 3 L per 24 h. The primary endpoint was post-ERCP pancreatitis and was analysed on a modified intention-to-treat basis (including all patients who underwent randomisation and an ERCP and for whom data regarding the primary outcome were available). The trial is registered with the ISRCTN registry, ISRCTN13659155. Findings: Between June 5, 2015, and June 6, 2019, 826 patients were randomly assigned, of whom 388 in the aggressive hydration group and 425 in the control group were included in the modified intention-to-treat analysis. Post-ERCP pancreatitis occurred in 30 (8%) patients in the aggressive hydration group and in 39 (9%) patients in the control group (relative risk 0·84, 95% CI 0·53–1·33, p=0·53). There were no differences in serious adverse events, including hydration-related complications (relative risk 0·99, 95% CI 0·59–1·64; p=1·00), ERCP-related complications (0·90, 0·62–1·31; p=0·62), intensive care unit admission (0·37, 0·07–1·80; p=0·22), and 30-day mortality (0·95, 0·50–1·83; p=1·00). Interpretation: Aggressive periprocedural hydration did not reduce the incidence of post-ERCP pancreatitis in patients with moderate to high risk of developing this complication who routinely received prophylactic rectal NSAIDs. Therefore, the burden of laborious and time-consuming aggressive periprocedural hydration to further reduce the risk of post-ERCP pancreatitis is not justified. Funding: Netherlands Organisation for Health Research and Development and Radboud University Medical Center.

UR - http://www.scopus.com/inward/record.url?scp=85104065517&partnerID=8YFLogxK

U2 - 10.1016/S2468-1253(21)00057-1

DO - 10.1016/S2468-1253(21)00057-1

M3 - Article

C2 - 33740415

AN - SCOPUS:85104065517

SN - 2468-1253

VL - 6

SP - 350

EP - 358

JO - The Lancet Gastroenterology and Hepatology

JF - The Lancet Gastroenterology and Hepatology

IS - 5

ER -

Sperna Weiland CJ, Smeets XJNM, the Dutch Pancreatitis Study Group, Kievit W, Verdonk RC, Poen AC et al. Aggressive fluid hydration plus non-steroidal anti-inflammatory drugs versus non-steroidal anti-inflammatory drugs alone for post-endoscopic retrograde cholangiopancreatography pancreatitis (FLUYT): a multicentre, open-label, randomised, controlled trial. The Lancet Gastroenterology and Hepatology. 2021 May;6(5):350-358. Epub 2021 Apr 12. doi: 10.1016/S2468-1253(21)00057-1

Aggressive fluid hydration plus non-steroidal anti-inflammatory drugs versus non-steroidal anti-inflammatory drugs alone for post-endoscopic retrograde cholangiopancreatography pancreatitis (FLUYT): a multicentre, open-label, randomised, controlled trial

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