Minimally invasive versus open pancreatoduodenectomy (LEOPARD-2): Study protocol for a randomized controlled trial

Thijs de Rooij, Jony van Hilst, Koop Bosscha, Marcel G. Dijkgraaf, Michael F. Gerhards, Bas Groot Koerkamp, Jeroen Hagendoorn, Ignace H. de Hingh, Tom M. Karsten, Daan J. Lips, Misha D. Luyer, I. Quintus Molenaar, Hjalmar C. van Santvoort, T. C.Khé Tran, Olivier R. Busch, Sebastiaan Festen, Marc G. Besselink*,

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

BACKGROUND: Data from observational studies suggest that minimally invasive pancreatoduodenectomy (MIPD) is superior to open pancreatoduodenectomy regarding intraoperative blood loss, postoperative morbidity, and length of hospital stay, without increasing total costs. However, several case-matched studies failed to demonstrate superiority of MIPD, and large registry studies from the USA even suggested increased mortality for MIPDs performed in low-volume (<10 MIPDs annually) centers. Randomized controlled multicenter trials are lacking but clearly required. We hypothesize that time to functional recovery is shorter after MIPD compared with open pancreatoduodenectomy, even in an enhanced recovery setting.

METHODS/DESIGN: LEOPARD-2 is a randomized controlled, parallel-group, patient-blinded, multicenter, phase 2/3, superiority trial in centers that completed the Dutch Pancreatic Cancer Group LAELAPS-2 training program for laparoscopic pancreatoduodenectomy or LAELAPS-3 training program for robot-assisted pancreatoduodenectomy and have performed ≥ 20 MIPDs. A total of 136 patients with symptomatic benign, premalignant, or malignant disease will be randomly assigned to undergo minimally invasive or open pancreatoduodenectomy in an enhanced recovery setting. After the first 40 patients (phase 2), the data safety monitoring board will assess safety outcomes (not blinded for treatment allocation) and decide on continuation to phase 3. Patients from phase 2 will then be included in phase 3. The primary outcome measure is time (days) to functional recovery. All patients will be blinded for the surgical approach, at least until postoperative day 5, but preferably until functional recovery has been attained. Secondary outcome measures are operative and postoperative outcomes, including clinically relevant complications, mortality, quality of life, and costs.

DISCUSSION: The LEOPARD-2 trial is designed to assess whether MIPD reduces time to functional recovery, as compared with open pancreatoduodenectomy in an enhanced recovery setting.

TRIAL REGISTRATION: Netherlands Trial Register, NTR5689 . Registered on 2 March 2016.

Original languageEnglish
Article number1
Pages (from-to)1-10
JournalTrials
Volume19
Issue number1
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • Laparoscopic
  • Minimally invasive
  • Pancreatoduodenectomy
  • Robot-assisted
  • Whipple
  • Humans
  • Postoperative Complications/etiology
  • Treatment Outcome
  • Pancreatic Diseases/diagnosis
  • Pancreaticoduodenectomy/adverse effects
  • Recovery of Function
  • Randomized Controlled Trials as Topic
  • Clinical Trials, Phase III as Topic
  • Netherlands
  • Multicenter Studies as Topic
  • Time Factors
  • Laparoscopy/adverse effects
  • Clinical Trials, Phase II as Topic
  • Robotic Surgical Procedures/adverse effects

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