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The ORANGE II PLUS - Trial: Open Versus Laparoscopic Hemihepatectomy

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by Maastricht University Medical Center
Sponsor:
Collaborators:
University Hospital Southampton NHS Foundation Trust
University Hospital, Ghent
San Raffaele University Hospital, Italy
Derriford Hospital
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Queen Elizabeth Hospital NHS Foundation Trust
King's College London
Newcastle-upon-Tyne Hospitals NHS Trust
Royal Free Hospital NHS Foundation Trust
Oslo University Hospital
General Hospital Groeninge
Jessa Hospital
Universitair Ziekenhuis Brussel
University Hospital, Aachen
Information provided by (Responsible Party):
Maastricht University Medical Center
ClinicalTrials.gov Identifier:
NCT01441856
First received: April 27, 2011
Last updated: September 12, 2016
Last verified: September 2016
  Purpose
The added value of the laparoscopic hemihepatectomy compared to the open hemihepatectomy has never been studied in a randomized controlled setting. Therefore, the multicenter international ORANGE II PLUS - trial has been constructed and will provide evidence on the merits of laparoscopic versus open hemihepatectomy in terms of time to functional recovery, hospital length of stay, intraoperative blood loss, operation time, resection margin, time to adjuvant chemotherapy initiation, readmission percentage, (liver-specific) morbidity, quality of life, body image, reasons for delay of discharge after functional recovery, long term incidence of incisional hernias, hospital and societal costs during one year and overall five-year survival.

Condition Intervention
Liver Lesions Requiring Hemihepatectomy
Procedure: Open or Laparoscopic left hemihepatectomy
Procedure: Open or Laparoscopic right hemihepatectomy

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: The ORANGE II PLUS - Trial: an International Multicenter Randomized Controlled Trial of Open Versus Laparoscopic Hemihepatectomies.

Further study details as provided by Maastricht University Medical Center:

Primary Outcome Measures:
  • Time to functional recovery [ Time Frame: expected average of 4-10 days ] [ Designated as safety issue: No ]
    Time until a patient is functionally recovered


Secondary Outcome Measures:
  • Length of hospital stay [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    Total length of hospital stay

  • Readmission percentage [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Total percentage of patients being readmitted

  • Total morbidity [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Total morbidity during one year

  • Composite endpoint of liver specific morbidity [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Composite endpoint of liver specific morbidity(intra-abdominal bleeding, intra-abdominal abcess, ascites, postresectional liver failure, intra-operative mortality, bile leakage)

  • Long term incidence of incisional hernia [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Incidence of incisional hernia after 1 year

  • Quality of life [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    QoL assessment (QLQ-C30 + LM 21) during one year

  • Body image and cosmesis [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Influence of intervention on body image and cosmesis during one year

  • Reasons for delay in discharge after functional recovery [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Intraoperative blood loss [ Time Frame: During procedure ] [ Designated as safety issue: No ]
  • Intraoperative time [ Time Frame: Surgical time from incision to closure ] [ Designated as safety issue: No ]
  • Resection margin [ Time Frame: During pathology assessment ] [ Designated as safety issue: No ]
  • Time to adjuvant chemotherapy initiation [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Hospital and societal cost [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • 5-year overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 250
Study Start Date: October 2013
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Open or Laparocopic Left
Open or Laparoscopic left hemihepatectomy
Procedure: Open or Laparoscopic left hemihepatectomy
Patients in this arm will undergo a left hemihepatectomy within an Enhanced Recovery After Surgery Program.
Active Comparator: Open or Laparoscopic Right
Open or Laparoscopic right hemihepatectomy
Procedure: Open or Laparoscopic right hemihepatectomy
Patients in this arm will undergo a right hemihepatectomy within an Enhanced Recovery After Surgery Program.
Active Comparator: Prospective registry
Prospective registry of patients that cannot be randomized (both open and laparoscopic left + right hemihepatectomy)
Procedure: Open or Laparoscopic left hemihepatectomy
Patients in this arm will undergo a left hemihepatectomy within an Enhanced Recovery After Surgery Program.
Procedure: Open or Laparoscopic right hemihepatectomy
Patients in this arm will undergo a right hemihepatectomy within an Enhanced Recovery After Surgery Program.

  Hide Detailed Description

Detailed Description:

Liver resection for colorectal metastasis is the only potentially curative therapy and has become the standard of care in appropriately staged patients, offering 5-year survival rates of approximately 35-40%. Also for symptomatic benign lesions and those of uncertain nature or large size, liver resection is a widely accepted treatment. Open hepatectomy (OH) is the current standard of care for the management of primary and secondary malignancies. Although the feasibility of laparoscopic hepatectomy (LH) has been established, only select centres have used this technique as their primary modality.

Laparoscopic liver resection was first reported in 1991. Over the last decade the method has gained wide acceptance for various liver resection procedures. Multiple retrospective case series and reviews comparing open with laparoscopic liver resection indicate that laparoscopic liver resection can be applied safely for both malignant and benign liver lesions. Laparoscopic liver resection has been associated with shorter hospital length of stay, reduced intraoperative blood loss, less postoperative pain, earlier recovery and better quality of life. Initially the left lateral segments of the liver were chosen for anatomic laparoscopic resection with good results. Many liver centres worldwide are currently adopting laparoscopic surgery for resection of anterior segments, but relatively low volumes to operate on, a significant learning curve and lack of evidence restrict the majority of liver surgeons to further adopt and disseminate this technique.

Recently, indications for resectability have been broadened by new (neo)adjuvant chemotherapies and (radio)embolisation techniques. A new impulse for the laparoscopic management of liver lesions came after the first reports of laparoscopic hemihepatectomies. Major hepatic resections can be technically demanding and hold an increased risk for morbidity. It was demonstrated that in expert hands major anatomical laparoscopic liver resections were feasible with good efficacy and safety. Expert liver centers are already performing laparoscopic (extended) hemihepatectomies. Currently, in European centers, a median hospital length of stay of 6.0 to 13.1 and 3.5 to 10.0 days is observed after respectively open and laparoscopic hepatic resection. In expert hands median duration of admission after major hepatic resection varies between 6 - 12.5 for open and 4 - 8.2 for laparoscopic surgery. However, reports are scarce and level 1 evidence on this matter is still to be presented.

Within the framework of optimising postoperative recovery, broader indications for resection and further adoption of laparoscopic liver surgery there is a need for a randomized trial.Regarding postoperative care, enthusiasm has arisen for the Enhanced Recovery After Surgery (ERAS®) program. This multimodal program, derived from Kehlet's 1990's pioneer work in the multimodal surgical care field, involves optimization of several aspects of the perioperative management of patients undergoing major abdominal surgery. In patients undergoing segmental colectomy, the ERAS® -program enabled earlier recovery and consequently shorter hospital length of stay. Furthermore, a reduction of postoperative morbidity in patients undergoing intestinal resection was reported. These results stimulated liver surgeons of the ERAS® group (Maastricht, Edinburgh and Tromsö) to adapt the ERAS®-program to patients undergoing open liver resection. Van Dam et al. found a significantly reduced hospital length of stay after open liver resection when patients were managed within a multimodal ERAS®-program. Besides a reduction of median total hospital length of stay from 8 to 6 days (25%), the data also suggested that a further reduction of stay could be possible as there was a delay between recovery and actual discharge of the patients. Moreover, Stoot et al. showed - retrospectively - a further reduction in length of stay from 7 days to 5 days when patients were operated laparoscopically and managed within an ERAS®-program. In this study there was also a delay between recovery and actual discharge of the patients. Earlier, Maessen et al. reported a median delay to discharge of 2 days after patients had functionally recovered from colonic surgery managed within an ERAS®-program. This delay is often linked to social problems, problems in homecare support or logistic problems.

The added value of the laparoscopic hemihepatectomy compared to the open hemihepatectomy has never been studied in a randomized controlled setting. Therefore, the multicenter international ORANGE II PLUS - trial has been constructed and will provide evidence on the merits of laparoscopic versus open hemihepatectomy.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients requiring open or laparoscopic left / right hemihepatectomy, with or without the need for one additional hepatic wedge resection or metastasectomy, for accepted indications.
  • Able to understand the nature of the study and what will be required of them.
  • Men and non-pregnant, non-lactating women age 18 years and older.
  • BMI between 18-35.
  • Patients with ASA I-II-III.

Exclusion Criteria:

  • Inability to give written informed consent.
  • Patients undergoing liver resection other than left or right hemihepatectomy, with or without the need for one additional hepatic wedge resection or metastasectomy.
  • Patients with hepatic lesion(s), that are located with insufficient margin from vascular or biliary structures to be operated laparoscopically.
  • Patients with ASA IV-V.
  • Repeat hepatectomy.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01441856

Contacts
Contact: R.S. Fichtinger, MD +31614921200 robert.fichtinger@mumc.nl
Contact: R.M. van Dam, MD PhD +31433877489 r.van.dam@mumc.nl

Locations
Belgium
Erasmus Hospital Recruiting
Brussels, Belgium
Contact: V. Lucidi, MD PhD         
Principal Investigator: V. Lucidi, MD PhD         
Sub-Investigator: G. Katsanos, MD PhD         
Ghent University Hospital Recruiting
Ghent, Belgium
Contact: R.I. Troisi, Prof.         
Principal Investigator: R.I. Troisi, Prof.         
Sub-Investigator: V. Scuderi, MD         
Jessa Hospital Recruiting
Hasselt, Belgium
Contact: G. Sergeant, MD PhD         
Principal Investigator: G. Sergeant, MD PhD         
General Hospital Groeninge Recruiting
Kortrijk, Belgium
Contact: M. D'Hondt, MD PhD         
Principal Investigator: M. D'Hondt, MD PhD         
Sub-Investigator: I. Boscart         
Germany
University Hospital Aachen Recruiting
Aachen, Germany
Contact: U.P. Neumann, Prof.         
Principal Investigator: U.P. Neumann, Prof.         
Sub-Investigator: F. Ulmer, MD PhD         
Italy
San Raffaele Hospital Recruiting
Milan, Italy
Contact: L. Aldrighetti, Prof.         
Principal Investigator: L. Aldrighetti, Prof.         
Sub-Investigator: F. Ratti, MD PhD         
Netherlands
Academic Medical Center Recruiting
Amsterdam, Netherlands
Contact: M.G. Besselink, MD PhD         
Principal Investigator: M.G. Besselink, MD PhD         
Sub-Investigator: P.J. Tanis, MD PhD         
Maastricht University Medical Center+ Recruiting
Maastricht, Netherlands
Contact: R. S. Fichtinger, MD MSc         
Principal Investigator: R.M. van Dam, MD PhD         
Sub-Investigator: R.S. Fichtinger, MD         
Norway
University Hospital Oslo Recruiting
Oslo, Norway
Contact: Å.A. Fretland, MD PhD         
Principal Investigator: B.E. Edwin, Prof.         
Sub-Investigator: Å.A. Fretland, MD PhD         
United Kingdom
Queen Elizabeth Hospital Recruiting
Birmingham, United Kingdom
Contact: R. Sutcliffe, MD PhD         
Principal Investigator: R. Sutcliffe, MD PhD         
Sub-Investigator: P. Marudanayagam, MD PhD         
Sub-Investigator: D. Bennett, MD PhD         
King's College Hospital Recruiting
London, United Kingdom
Contact: K.V. Menon, MD PhD         
Principal Investigator: K.V. Menon, MD PhD         
Sub-Investigator: A. Ayers, MD PhD         
Royal Free Hospital Active, not recruiting
London, United Kingdom
Freeman Hospital Recruiting
Newcastle, United Kingdom
Contact: S. A. White, Prof.         
Principal Investigator: S. A. White, Prof.         
Sub-Investigator: S. M. Robinson, MD PhD         
Derriford Hospital Recruiting
Plymouth, United Kingdom
Contact: S. Aroori, MD PhD         
Principal Investigator: S. Aroori, MD PhD         
Sub-Investigator: C. Briggs, MD PhD         
University Hospital Southampton Recruiting
Southampton, United Kingdom
Contact: J.N. Primrose, Prof.         
Principal Investigator: M. Abu Hilal, MD PhD         
Sub-Investigator: A.S. Takhar, MD PhD         
Sub-Investigator: T.H. Armstrong, MD PhD         
Sub-Investigator: Z.R. Hamady, MD PhD         
Sponsors and Collaborators
Maastricht University Medical Center
University Hospital Southampton NHS Foundation Trust
University Hospital, Ghent
San Raffaele University Hospital, Italy
Derriford Hospital
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Queen Elizabeth Hospital NHS Foundation Trust
King's College London
Newcastle-upon-Tyne Hospitals NHS Trust
Royal Free Hospital NHS Foundation Trust
Oslo University Hospital
General Hospital Groeninge
Jessa Hospital
Universitair Ziekenhuis Brussel
University Hospital, Aachen
Investigators
Principal Investigator: R.M. van Dam, MD PhD Maastricht University Medical Center
  More Information

Responsible Party: Maastricht University Medical Center
ClinicalTrials.gov Identifier: NCT01441856     History of Changes
Other Study ID Numbers: NL36215.068.11 
Study First Received: April 27, 2011
Last Updated: September 12, 2016
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Maastricht University Medical Center:
Open
Laparoscopic
Hemihepatectomy
Enhanced Recovery After Surgery
Functional recovery

ClinicalTrials.gov processed this record on December 07, 2016