Minimally invasive versus open pancreatoduodenectomy for pancreatic and peri-ampullary neoplasm (DIPLOMA-2): study protocol for an international multicenter patient-blinded randomized controlled trial.
Laparoscopic
Minimally invasive
Pancreatic cancer
Pancreatic ductal adenocarcinoma
Pancreatic surgery
Pancreatoduodenectomy
Peri-ampullary cancer
Robot-assisted
Whipple
Journal
Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253
Informations de publication
Date de publication:
12 Oct 2023
12 Oct 2023
Historique:
received:
15
06
2023
accepted:
16
09
2023
medline:
1
11
2023
pubmed:
13
10
2023
entrez:
12
10
2023
Statut:
epublish
Résumé
Minimally invasive pancreatoduodenectomy (MIPD) aims to reduce the negative impact of surgery as compared to open pancreatoduodenectomy (OPD) and is increasingly becoming part of clinical practice for selected patients worldwide. However, the safety of MIPD remains a topic of debate and the potential shorter time to functional recovery needs to be confirmed. To guide safe implementation of MIPD, large-scale international randomized trials comparing MIPD and OPD in experienced high-volume centers are needed. We hypothesize that MIPD is non-inferior in terms of overall complications, but superior regarding time to functional recovery, as compared to OPD. The DIPLOMA-2 trial is an international randomized controlled, patient-blinded, non-inferiority trial performed in 14 high-volume pancreatic centers in Europe with a minimum annual volume of 30 MIPD and 30 OPD. A total of 288 patients with an indication for elective pancreatoduodenectomy for pre-malignant and malignant disease, eligible for both open and minimally invasive approach, are randomly allocated for MIPD or OPD in a 2:1 ratio. Centers perform either laparoscopic or robot-assisted MIPD based on their surgical expertise. The primary outcome is the Comprehensive Complication Index (CCI®), measuring all complications graded according to the Clavien-Dindo classification up to 90 days after surgery. The sample size is calculated with the following assumptions: 2.5% one-sided significance level (α), 80% power (1-β), expected difference of the mean CCI® score of 0 points between MIPD and OPD, and a non-inferiority margin of 7.5 points. The main secondary outcome is time to functional recovery, which will be analyzed for superiority. Other secondary outcomes include post-operative 90-day Fitbit™ measured activity, operative outcomes (e.g., blood loss, operative time, conversion to open surgery, surgeon-reported outcomes), oncological findings in case of malignancy (e.g., R0-resection rate, time to adjuvant treatment, survival), postoperative outcomes (e.g., clinically relevant complications), healthcare resource utilization (length of stay, readmissions, intensive care stay), quality of life, and costs. Postoperative follow-up is up to 36 months. The DIPLOMA-2 trial aims to establish the safety of MIPD as the new standard of care for this selected patient population undergoing pancreatoduodenectomy in high-volume centers, ultimately aiming for superior patient recovery. ISRCTN27483786. Registered on August 2, 2023.
Sections du résumé
BACKGROUND
BACKGROUND
Minimally invasive pancreatoduodenectomy (MIPD) aims to reduce the negative impact of surgery as compared to open pancreatoduodenectomy (OPD) and is increasingly becoming part of clinical practice for selected patients worldwide. However, the safety of MIPD remains a topic of debate and the potential shorter time to functional recovery needs to be confirmed. To guide safe implementation of MIPD, large-scale international randomized trials comparing MIPD and OPD in experienced high-volume centers are needed. We hypothesize that MIPD is non-inferior in terms of overall complications, but superior regarding time to functional recovery, as compared to OPD.
METHODS/DESIGN
METHODS
The DIPLOMA-2 trial is an international randomized controlled, patient-blinded, non-inferiority trial performed in 14 high-volume pancreatic centers in Europe with a minimum annual volume of 30 MIPD and 30 OPD. A total of 288 patients with an indication for elective pancreatoduodenectomy for pre-malignant and malignant disease, eligible for both open and minimally invasive approach, are randomly allocated for MIPD or OPD in a 2:1 ratio. Centers perform either laparoscopic or robot-assisted MIPD based on their surgical expertise. The primary outcome is the Comprehensive Complication Index (CCI®), measuring all complications graded according to the Clavien-Dindo classification up to 90 days after surgery. The sample size is calculated with the following assumptions: 2.5% one-sided significance level (α), 80% power (1-β), expected difference of the mean CCI® score of 0 points between MIPD and OPD, and a non-inferiority margin of 7.5 points. The main secondary outcome is time to functional recovery, which will be analyzed for superiority. Other secondary outcomes include post-operative 90-day Fitbit™ measured activity, operative outcomes (e.g., blood loss, operative time, conversion to open surgery, surgeon-reported outcomes), oncological findings in case of malignancy (e.g., R0-resection rate, time to adjuvant treatment, survival), postoperative outcomes (e.g., clinically relevant complications), healthcare resource utilization (length of stay, readmissions, intensive care stay), quality of life, and costs. Postoperative follow-up is up to 36 months.
DISCUSSION
CONCLUSIONS
The DIPLOMA-2 trial aims to establish the safety of MIPD as the new standard of care for this selected patient population undergoing pancreatoduodenectomy in high-volume centers, ultimately aiming for superior patient recovery.
TRIAL REGISTRATION
BACKGROUND
ISRCTN27483786. Registered on August 2, 2023.
Identifiants
pubmed: 37828593
doi: 10.1186/s13063-023-07657-7
pii: 10.1186/s13063-023-07657-7
pmc: PMC10571285
doi:
Types de publication
Clinical Trial Protocol
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
665Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
Références
Gagner M, Pomp A. Laparoscopic pylorus-preserving pancreatoduodenectomy. Surg Endosc. 1994;8(5):408–10.
doi: 10.1007/BF00642443
pubmed: 7915434
Kendrick ML. Laparoscopic and robotic resection for pancreatic cancer. Cancer J. 2012;18(6):571–6.
doi: 10.1097/PPO.0b013e31827b8f86
pubmed: 23187844
Giulianotti PC, et al. Robotics in general surgery: personal experience in a large community hospital. Arch Surg. 2003;138(7):777–84.
doi: 10.1001/archsurg.138.7.777
pubmed: 12860761
Poves, I., et al. Comparison of perioperative outcomes between laparoscopic and open approach for pancreatoduodenectomy: The Padulap randomized controlled trial.
Palanivelu, C., et al., Randomized clinical trial of laparoscopic versus open pancreatoduodenectomy for periampullary tumours. British Journal of Surgery, 2017.
van Hilst, J., et al., Laparoscopic versus open pancreatoduodenectomy for pancreatic or periampullary tumours (LEOPARD-2): a multicentre, patient-blinded, randomised controlled phase 2/3 trial. The Lancet Gastroenterology and Hepatology, 2019.
Wang M, et al. Laparoscopic versus open pancreatoduodenectomy for pancreatic or periampullary tumours: a multicentre, open-label, randomised controlled trial. Lancet Gastroenterol Hepatol. 2021;6(6):438–47.
doi: 10.1016/S2468-1253(21)00054-6
pubmed: 33915091
Peters BS, et al. Review of emerging surgical robotic technology. Surg Endosc. 2018;32(4):1636–55.
doi: 10.1007/s00464-018-6079-2
Joyce D, et al. Robotic surgery of the pancreas. World J Gastroenterol. 2014;20(40):14726–32.
doi: 10.3748/wjg.v20.i40.14726
pubmed: 25356035
pmcid: 4209538
Zureikat, A.H., et al., 500 minimally invasive robotic pancreatoduodenectomies. Annals of Surgery, 2019.
McMillan MT, et al. A propensity score-matched analysis of robotic vs open pancreatoduodenectomy on incidence of pancreatic fistula. JAMA Surg. 2017;152(4):327–35.
doi: 10.1001/jamasurg.2016.4755
pubmed: 28030724
pmcid: 5470429
Napoli, N., et al., Robotic versus open pancreatoduodenectomy: a propensity score-matched analysis based on factors predictive of postoperative pancreatic fistula. Surgical Endoscopy, 2018.
Weng Y, et al. Oncological outcomes of robotic-assisted versus open pancreatoduodenectomy for pancreatic ductal adenocarcinoma: a propensity score-matched analysis. Surg Endosc. 2021;35(7):3437–48.
doi: 10.1007/s00464-020-07791-2
pubmed: 32696148
Asbun, H.J., et al., The Miami International Evidence-based Guidelines on Minimally Invasive Pancreas Resection. Annals of Surgery, 2020.
Adam MA, et al. Defining a hospital volume threshold for minimally invasive pancreaticoduodenectomy in the United States. JAMA Surg. 2017;152(4):336–42.
doi: 10.1001/jamasurg.2016.4753
pubmed: 28030713
Chan, A.W., et al., SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ (Clinical research ed.), 2013.
Schneider A, Lohr JM, Singer MV. The M-ANNHEIM classification of chronic pancreatitis: introduction of a unifying classification system based on a review of previous classifications of the disease. J Gastroenterol. 2007;42(2):101–19.
doi: 10.1007/s00535-006-1945-4
pubmed: 17351799
Montagnini AL, et al. Standardizing terminology for minimally invasive pancreatic resection. HPB (Oxford). 2017;19(3):182–9.
doi: 10.1016/j.hpb.2017.01.006
pubmed: 28317657
Wong-Lun-Hing EM, et al. Randomized clinical trial of open versus laparoscopic left lateral hepatic sectionectomy within an enhanced recovery after surgery programme (ORANGE II study). Br J Surg. 2017;104(5):525–35.
doi: 10.1002/bjs.10438
pubmed: 28138958
de Rooij, T., et al., Minimally invasive versus open distal pancreatectomy (LEOPARD): a multicenter patient-blinded randomized controlled trial. Ann Surg, 2018.
de Rooij T, et al. Minimally invasive versus open pancreatoduodenectomy (LEOPARD-2): study protocol for a randomized controlled trial. Trials. 2018;19(1):1.
doi: 10.1186/s13063-017-2423-4
pubmed: 29298706
pmcid: 5753506
Bang H, Ni L, Davis CE. Assessment of blinding in clinical trials. Control Clin Trials. 2004;25(2):143–56.
doi: 10.1016/j.cct.2003.10.016
pubmed: 15020033
Slankamenac, K., et al., The comprehensive complication index: a novel continuous scale to measure surgical morbidity. Annals of Surgery, 2013.
Slankamenac, K., et al. The comprehensive complication index a novel and more sensitive endpoint for assessing outcome and reducing sample size in randomized controlled trials.
Dindo, D., N. Demartines, and P.A. Clavien, Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. 2004.
De Boer, C., et al., Utility of wearable sensors to assess postoperative recovery in pediatric patients after appendectomy. Journal of Surgical Research, 2021.
Jonker, L.T., et al., Postoperative recovery of accelerometer-based physical activity in older cancer patients. Eur J Surg Oncol, 2020.
Kim, D.H., et al., The usefulness of a wearable device in daily physical activity monitoring for the hospitalized patients undergoing lumbar surgery. J Korean Neurosurg Soc, 2019.
Symer, M.M., et al., A mobile health application to track patients after gastrointestinal surgery: results from a pilot study. J Gastrointest Surg, 2017.
Bassi C, et al. The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 Years After. Surgery. 2017;161(3):584–91.
doi: 10.1016/j.surg.2016.11.014
pubmed: 28040257
Wente MN, et al. Postpancreatectomy hemorrhage (PPH): an International Study Group of Pancreatic Surgery (ISGPS) definition. Surgery. 2007;142(1):20–5.
doi: 10.1016/j.surg.2007.02.001
pubmed: 17629996
Wente MN, et al. Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS). Surgery. 2007;142(5):761–8.
doi: 10.1016/j.surg.2007.05.005
pubmed: 17981197
Besselink MG, et al. Definition and classification of chyle leak after pancreatic operation: a consensus statement by the International Study Group on Pancreatic Surgery. Surgery. 2017;161(2):365–72.
doi: 10.1016/j.surg.2016.06.058
pubmed: 27692778
Mangram AJ, et al. Guideline for Prevention of Surgical Site Infection, 1999. Centers for Disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory Committee. Am J Infect Control. 1999;27(2):97–132 discussion 96.
doi: 10.1016/S0196-6553(99)70088-X
pubmed: 10196487
Cancer, t.A.J.C.o., American Joint Committee on Cancer classification 7th edition.
Fitzsimmons, D., et al., Development of a disease specific quality of life (QoL) questionnaire module to supplement the EORTC core cancer QoL questionnaire, the QLQ-C30 in patients with pancreatic cancer. Eur J Cancer, 1999.
Müller-Nordhorn, J., et al., Health-related quality of life in patients with pancreatic cancer. Digestion, 2007.
Mor V, et al. The Karnofsky Performance Status Scale. An examination of its reliability and validity in a research setting. Cancer. 1984;53(9):2002–7.
doi: 10.1002/1097-0142(19840501)53:9<2002::AID-CNCR2820530933>3.0.CO;2-W
pubmed: 6704925
Schuh F, et al. A Simple Classification of Pancreatic Duct Size and Texture Predicts Postoperative Pancreatic Fistula: a classification of the International Study Group of Pancreatic Surgery. Ann Surg. 2023;277(3):e597–608.
doi: 10.1097/SLA.0000000000004855
pubmed: 33914473
Suurmeijer JA, et al. Nationwide validation of the ISGPS risk classification for postoperative pancreatic fistula after pancreatoduodenectomy: “Less is more.” Surgery. 2023;173(5):1248–53.
doi: 10.1016/j.surg.2023.01.004
pubmed: 36858874
Moekotte AL, et al. Safe implementation of minimally invasive pancreas resection: a systematic review. HPB (Oxford). 2020;22(5):637–48.
doi: 10.1016/j.hpb.2019.11.005
pubmed: 31836284
Probst P, et al. Evidence-based recommendations for blinding in surgical trials. Langenbecks Arch Surg. 2019;404(3):273–84.
doi: 10.1007/s00423-019-01761-6
pubmed: 30824993
De Rooij, T., et al., Minimally invasive versus open distal pancreatectomy (LEOPARD): a multicenter patient-blinded randomized controlled trial. Annals of Surgery, 2019.
van Dam, R.M., et al., Open versus laparoscopic left lateral hepatic sectionectomy within an enhanced recovery ERAS® programme (ORANGE II - Trial): Study protocol for a randomised controlled trial. Trials, 2012.