Minimally invasive versus open pancreatoduodenectomy for pancreatic and peri-ampullary neoplasm (DIPLOMA-2): study protocol for an international multicenter patient-blinded randomized controlled trial

Trials

Study Protocol

Sebastiaan Festen¹  Johannes Berkhof²  Mohammad Abu Hilal³  Marco Ramera³  Clarissa Ferrari³  Nine de Graaf⁴  Caro L. Bruna⁴  Anouk M. L. H. Emmen⁴  Mirjam A. G. Sprangers⁵  Mathieu D’Hondt⁶  Marc G. Besselink⁷  Olivier R. Busch⁷  Freek Daams⁷  Jony van Hilst⁸  Misha D. P. Luyer⁹  Bas Groot Koerkamp^1,10  Benedetto Ielpo^1,11  J. Sven D. Mieog^1,12  Bergthor Björnsson^1,13  Daan J. Lips^1,14  Igor E. Khatkov^1,15  Giovanni Ferrari^1,16  Tobias Keck^1,17  I. Quintus Molenaar^1,18  Hjalmar C. van Santvoort^1,18  Ugo Boggi^1,19  Patrick Maisonneuve^2,20  Luca Morelli^2,21 

[1] Cancer Center Amsterdam, Amsterdam, the Netherlands;Department of Epidemiology and Data Science, Amsterdam UMC, VU University, Amsterdam, the Netherlands;Department of General Surgery, Fondazione Poliambulanza Istituto Ospedaliero, 25123, Brescia, Italy;Department of General Surgery, Fondazione Poliambulanza Istituto Ospedaliero, 25123, Brescia, Italy;Department of Surgery, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands;Cancer Center Amsterdam, Amsterdam, the Netherlands;Department of Medical Psychology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands;Department of Surgery, AZ Groeninge, Kortrijk, Belgium;Department of Surgery, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands;Cancer Center Amsterdam, Amsterdam, the Netherlands;Department of Surgery, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands;Cancer Center Amsterdam, Amsterdam, the Netherlands;Department of Surgery, OLVG, Amsterdam, the Netherlands;Department of Surgery, Catharina Ziekenhuis, Eindhoven, the Netherlands;Department of Surgery, Erasmus MC, Rotterdam, the Netherlands;Department of Surgery, Hospital del Mar, Barcelona, Spain;Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands;Department of Surgery, Linköping University Hospital, Linköping, Sweden;Department of Surgery, Medisch Spectrum Twente, Enschede, the Netherlands;Department of Surgery, Moscow Clinical Scientific Center, Moscow, Russian Federation;Department of Surgery, Niguarda Ca’Granda Hospital, Milan, Italy;Department of Surgery, UKSH Campus Lübeck, Lübeck, Germany;Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands;Department of Surgery, St. Antonius Hospital, Nieuwegein, the Netherlands;Department of Surgery, Universitá Di Pisa, Pisa, Italy;Division of Epidemiology and Biostatistics, IEO European Institute of Oncology IRCCS, Milan, Italy;General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy;

关键词: Minimally invasive;    Laparoscopic;    Robot-assisted;    Pancreatoduodenectomy;    Whipple;    Pancreatic surgery;    Pancreatic cancer;    Peri-ampullary cancer;    Pancreatic ductal adenocarcinoma;   

DOI  :  10.1186/s13063-023-07657-7

 received in 2023-06-15, accepted in 2023-09-16,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundMinimally 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/designThe 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.DiscussionThe 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 registrationISRCTN27483786. Registered on August 2, 2023

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

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