TY - JOUR
T1 - Minimally invasive versus open pancreatoduodenectomy for pancreatic and peri-ampullary neoplasm (DIPLOMA-2)
T2 - study protocol for an international multicenter patient-blinded randomized controlled trial
AU - de Graaf, Nine
AU - Emmen, Anouk M.L.H.
AU - Ramera, Marco
AU - Björnsson, Bergthor
AU - Boggi, Ugo
AU - Bruna, Caro L.
AU - Busch, Olivier R.
AU - Daams, Freek
AU - Ferrari, Giovanni
AU - Festen, Sebastiaan
AU - van Hilst, Jony
AU - D’Hondt, Mathieu
AU - Ielpo, Benedetto
AU - Keck, Tobias
AU - Khatkov, Igor E.
AU - Koerkamp, Bas Groot
AU - Lips, Daan J.
AU - Luyer, Misha D.P.
AU - Mieog, J. Sven D.
AU - Morelli, Luca
AU - Molenaar, I. Quintus
AU - van Santvoort, Hjalmar C.
AU - Sprangers, Mirjam A.G.
AU - Ferrari, Clarissa
AU - Berkhof, Johannes
AU - Maisonneuve, Patrick
AU - Abu Hilal, Mohammad
AU - Besselink, Marc G.
N1 - Funding:
Intuitive Surgical Sarl. (Switzerland) fnancially supported the investigatorinitiated DIPLOMA-2 trial (reference number I). The funder had no infuence on
the study design and will not have infuence on data collection, interpretation
of data, manuscript development, or the decision to publish.
Publisher Copyright:
© 2023, BioMed Central Ltd., part of Springer Nature.
PY - 2023/10/12
Y1 - 2023/10/12
N2 - 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: 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: 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: ISRCTN27483786. Registered on August 2, 2023.
AB - 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: 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: 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: ISRCTN27483786. Registered on August 2, 2023.
UR - http://www.scopus.com/inward/record.url?scp=85174154451&partnerID=8YFLogxK
U2 - 10.1186/s13063-023-07657-7
DO - 10.1186/s13063-023-07657-7
M3 - Article
C2 - 37828593
AN - SCOPUS:85174154451
SN - 1745-6215
VL - 24
JO - Trials
JF - Trials
IS - 1
M1 - 665
ER -