Download PDF
Endoscopy 2025; 57(11): 1243-1250
DOI: 10.1055/a-2637-3180
Original article

The effect of prophylactic clipping on delayed bleeding after proximal colonic endoscopic mucosal resection: a multicenter, randomized controlled trial (CLIPPER)

Authors

  • Gijs Kemper 

    1   Department of Gastroenterology and Hepatology, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, Netherlands

  • Ayla S. Turan

    1   Department of Gastroenterology and Hepatology, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, Netherlands

  • Ramon-Michel Schreuder

    2   Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, Netherlands

  • Ruud W. M. Schrauwen

    3   Department of Gastroenterology and Hepatology, Bernhoven, Uden, Netherlands

  • Muhammed Hadithi

    4   Department of Gastroenterology and Hepatology, Maasstad Hospital, Rotterdam, Netherlands

  • Paul Didden

    5   Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, Netherlands

  • Barbara A. J. Bastiaansen

    6   Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, Netherlands

  • Bas W. van der Spek 

    7   Department of Gastroenterology and Hepatology, Noordwest Hospital Group, Alkmaar, Netherlands

  • Jochim S. Terhaar sive Droste

    8   Department of Gastroenterology and Hepatology, Jeroen Bosch Hospital, s' Hertogenbosch, Netherlands

  • Matthijs P. Schwartz

    9   Department of Gastroenterology and Hepatology, Meander Medical Center, Amersfoort, Netherlands

  • Wouter L. Hazen

    10   Department of Gastroenterology and Hepatology, Elisabeth-TweeSteden Hospital, Tilburg, Netherlands

  • Jan Willem A. Straathof

    11   Department of Gastroenterology and Hepatology, Máxima Medical Center, Veldhoven, Netherlands

  • Jurjen J. Boonstra

    12   Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, Netherlands

  • Alaa Alkhalaf

    13   Department of Gastroenterology and Hepatology, Isala Clinics, Zwolle, Netherlands

  • Fia J. Voogd

    14   Department of Gastroenterology and Hepatology, Medical Center Leeuwarden, Leeuwarden, Netherlands

  • Daud Allajar

    15   Department of Gastroenterology and Hepatology, Hospital St. Jansdal, Harderwijk, Netherlands

  • Wilmar de Graaf

    16   Department of Gastroenterology and Hepatology, Erasmus MC – University Medical Center, Rotterdam, Netherlands

  • Parweez Koehestanie

    17   Department of Gastroenterology and Hepatology, BRAVIS Hospital, Roosendaal, Netherlands

  • Robert Roomer

    18   Department of Gastroenterology and Hepatology, Franciscus Gasthuis & Vlietland, Rotterdam, Netherlands

  • Rogier J. J. de Ridder

    19   Department of Gastroenterology and Hepatology, Maastricht University Medical Center+, Maastricht, Netherlands

  • Leon M. G. Moons

    5   Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, Netherlands

  • Peter D. Siersema

    1   Department of Gastroenterology and Hepatology, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, Netherlands
    16   Department of Gastroenterology and Hepatology, Erasmus MC – University Medical Center, Rotterdam, Netherlands

  • Erwin J. M. van Geenen

    1   Department of Gastroenterology and Hepatology, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, Netherlands
    • Dutch EMR Study Group

Supported by: Maag Lever Darm Stichting http://dx.doi.org/10.13039/501100008359 Trial Registration: ClinicalTrials.gov Registration number (trial ID): NCT03309683 Type of study: Multicenter randomized crossover trial
Further Information
Also available at
   Permissions and Reprints


Graphical Abstract

Preview

Referred to by:

Prophylactic clip closure after endoscopic mucosal resection in the proximal colon: are we missing the mark or just the right technique?Endoscopy 2025; 57(11): 1251-1253
DOI: 10.1055/a-2662-7940

Abstract

Background Delayed bleeding is the most common complication after endoscopic mucosal resection (EMR) of large colorectal polyps. Randomized controlled trials in high volume centers have suggested that prophylactic clipping of the resection defect reduces delayed bleeding in patients with a high risk for delayed bleeding. We aimed to evaluate the role of prophylactic clipping in reducing delayed bleeding in patients undergoing EMR for large, proximal, nonpedunculated polyps in daily clinical practice.

Methods We performed a randomized controlled trial in 19 Dutch hospitals in patients referred for EMR of laterally spreading and sessile polyps ≥ 20 mm in the proximal colon. Patients were randomly assigned (1:1) into groups receiving or not receiving prophylactic clipping. The primary end point was delayed bleeding, and analyses were performed according to intention-to-treat analysis. The trial was registered at ClinicalTrials.gov (NCT03309683).

Results Between May 2018 and December 2021, 356 patients with a median polyp size of 30 mm (interquartile range 25–40) in the proximal colon were randomized (177 to the prophylactic clipping group and 179 to the control group). Delayed bleeding occurred in 16 patients (9.0 %) receiving prophylactic clipping and 11 control patients (6.1 %; P  = 0.30). No deaths were reported.

Conclusions Prophylactic clipping did not reduce delayed bleeding in patients undergoing EMR for large laterally spreading and sessile polyps in the proximal colon in daily clinical practice.

Supplementary Material



Publication History

Received: 18 September 2024

Accepted after revision: 20 May 2025

Article published online:
22 July 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

  • References

  • 1 Citarda F, Tomaselli G, Capocaccia R. et al. Efficacy in standard clinical practice of colonoscopic polypectomy in reducing colorectal cancer incidence. Gut 2001; 48: 812-815
    Search in Google Scholar
  • 2 Kaltenbach T, Anderson JC, Burke CA. et al. Endoscopic removal of colorectal lesions: recommendations by the US Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol 2020; 115: 435-464
    Search in Google Scholar
  • 3 Ferlitsch M, Moss A, Hassan C. et al. Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy 2017; 49: 270-297
    Search in Google Scholar
  • 4 Conio M, Repici A, Demarquay JF. et al. EMR of large sessile colorectal polyps. Gastrointest Endosc 2004; 60: 234-241
    Search in Google Scholar
  • 5 Ferrara F, Luigiano C, Ghersi S. et al. Efficacy, safety and outcomes of ‘inject and cut’ endoscopic mucosal resection for large sessile and flat colorectal polyps. Digestion 2010; 82: 213-220
    Search in Google Scholar
  • 6 Moss A, Bourke MJ, Williams SJ. et al. Endoscopic mucosal resection outcomes and prediction of submucosal cancer from advanced colonic mucosal neoplasia. Gastroenterology 2011; 140: 1909-1918
    Search in Google Scholar
  • 7 Bahin FF, Naidoo M, Williams SJ. et al. Prophylactic endoscopic coagulation to prevent bleeding after wide-field endoscopic mucosal resection of large sessile colon polyps. Clin Gastroenterol Hepatol 2015; 13: 724-730.e1-2
    Search in Google Scholar
  • 8 Burgess NG, Metz AJ, Williams SJ. et al. Risk factors for intraprocedural and clinically significant delayed bleeding after wide-field endoscopic mucosal resection of large colonic lesions. Clin Gastroenterol Hepatol 2014; 12: 651-661.e1-3
    Search in Google Scholar
  • 9 Lee CK, Lee SH, Park JY. et al. Prophylactic argon plasma coagulation ablation does not decrease delayed postpolypectomy bleeding. Gastrointest Endosc 2009; 70: 353-361
    Search in Google Scholar
  • 10 Metz AJ, Bourke MJ, Moss A. et al. Factors that predict bleeding following endoscopic mucosal resection of large colonic lesions. Endoscopy 2011; 43: 506-511
    Search in Google Scholar
  • 11 van der Star S, Moons LMG, Ter Borg F. et al. Management of delayed bleeding after endoscopic mucosal resection of large colorectal polyps: a retrospective multi-center cohort study. Endosc Int Open 2020; 8: E1052-E1060
    Search in Google Scholar
  • 12 Burgess NG, Williams SJ, Hourigan LF. et al. A management algorithm based on delayed bleeding after wide-field endoscopic mucosal resection of large colonic lesions. Clin Gastroenterol Hepatol 2014; 12: 1525-1533
    Search in Google Scholar
  • 13 Liaquat H, Rohn E, Rex DK. Prophylactic clip closure reduced the risk of delayed postpolypectomy hemorrhage: experience in 277 clipped large sessile or flat colorectal lesions and 247 control lesions. Gastrointest Endosc 2013; 77: 401-407
    Search in Google Scholar
  • 14 Takizawa K, Oda I, Gotoda T. et al. Routine coagulation of visible vessels may prevent delayed bleeding after endoscopic submucosal dissection – an analysis of risk factors. Endoscopy 2008; 40: 179-183
    Search in Google Scholar
  • 15 Huang R, Pan Y, Hui N. et al. Polysaccharide hemostatic system for hemostasis management in colorectal endoscopic mucosal resection. Dig Endosc 2014; 26: 63-68
    Search in Google Scholar
  • 16 Forbes N, Frehlich L, James MT. et al. Routine prophylactic endoscopic clipping is not efficacious in the prevention of delayed post-polypectomy bleeding: a systematic review and meta-analysis of randomized controlled trials. J Can Assoc Gastroenterol 2019; 2: 105-117
    Search in Google Scholar
  • 17 Turan AS, Pohl H, Matsumoto M. et al. The role of clips in preventing delayed bleeding after colorectal polyp resection: an individual patient data meta-analysis. Clin Gastroenterol Hepatol 2022; 20: 362-371.e23
    Search in Google Scholar
  • 18 Gupta S, Sidhu M, Shahidi N. et al. Effect of prophylactic endoscopic clip placement on clinically significant post-endoscopic mucosal resection bleeding in the right colon: a single-centre, randomised controlled trial. Lancet Gastroenterol Hepatol 2022; 7: 152-160
    Search in Google Scholar
  • 19 Endoscopic Classification Review Group. Update on the Paris classification of superficial neoplastic lesions in the digestive tract. Endoscopy 2005; 37: 570-578
    Search in Google Scholar
  • 20 Turan AS, Moons LMG, Schreuder RM. et al. Clip placement to prevent delayed bleeding after colonic endoscopic mucosal resection (CLIPPER): study protocol for a randomized controlled trial. Trials 2021; 22: 63
    Search in Google Scholar
  • 21 Brouwer MA. Beleid antitrombotische therapie rondom endoscopische procedures. 2016. Haarlem: Nederlandse Vereniging van Maag-Darm-Leverartsen (Dutch Association of Gastroenterologists); 2016. Accessed: May 21, 2025. https://www.mdl.nl/sites/www.mdl.nl/files/richlijnen/Richtlijn_antitrombotische_therapie_final_mei_2016.pdf
  • 22 Parra-Blanco A, Kaminaga N, Kojima T. et al. Hemoclipping for postpolypectomy and postbiopsy colonic bleeding. Gastrointest Endosc 2000; 51: 37-41
    Search in Google Scholar
  • 23 Cotton PB, Eisen GM, Aabakken L. et al. A lexicon for endoscopic adverse events: report of an ASGE workshop. Gastrointest Endosc 2010; 71: 446-454
    Search in Google Scholar
  • 24 Albeniz E, Álvarez MA, Espinós JC. et al. Clip closure after resection of large colorectal lesions with substantial risk of bleeding. Gastroenterology 2019; 157: 1213-1221.e4
    Search in Google Scholar
  • 25 Pohl H, Grimm IS, Moyer MT. et al. Clip closure prevents bleeding after endoscopic resection of large colon polyps in a randomized trial. Gastroenterology 2019; 157: 977-984.e3
    Search in Google Scholar
  • 26 Feagins LA, Smith AD, Kim D. et al. Efficacy of prophylactic hemoclips in prevention of delayed post-polypectomy bleeding in patients with large colonic polyps. Gastroenterology 2019; 157: 967-976.e1
    Search in Google Scholar
  • 27 Forbes N, Gupta S, Frehlich L. et al. Clip closure to prevent adverse events after EMR of proximal large nonpedunculated colorectal polyps: meta-analysis of individual patient data from randomized controlled trials. Gastrointest Endosc 2022; 96: 721-731.e2
    Search in Google Scholar
  • 28 Osada T, Sakamoto N, Ritsuno H. et al. Closure with clips to accelerate healing of mucosal defects caused by colorectal endoscopic submucosal dissection. Surg Endosc 2016; 30: 4438-4444
    Search in Google Scholar
  • 29 Yu Z, Albéniz E, Hu J. et al. Prevention of delayed post-polypectomy bleeding by prophylactic clipping after endoscopic colorectal polypectomy: a meta-analysis. Int J Colorectal Dis 2022; 37: 2229-2236
    Search in Google Scholar
  • 30 Spadaccini M, Albéniz E, Pohl H. et al. Prophylactic clipping after colorectal endoscopic resection prevents bleeding of large, proximal polyps: meta-analysis of randomized trials. Gastroenterology 2020; 159: 148-158.e11
    Search in Google Scholar
  • 31 Chen B, Du L, Luo L. et al. Prophylactic clips to reduce delayed polypectomy bleeding after resection of large colorectal polyps: a systematic review and meta-analysis of randomized trials. Gastrointest Endosc 2021; 93: 807-815
    Search in Google Scholar