The ORANGE II PLUS - Trial: Open Versus Laparoscopic Hemihepatectomy

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ClinicalTrials.gov Identifier: NCT01441856

Recruitment Status : Active, not recruiting

First Posted : September 28, 2011

Last Update Posted : March 9, 2021

View this study on Beta.ClinicalTrials.gov

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

Oslo University Hospital

General Hospital Groeninge

Jessa Hospital

Universitair Ziekenhuis Brussel

University Hospital, Aachen

Liverpool University Hospitals NHS Foundation Trust

Oxford University Hospitals NHS Trust

Information provided by (Responsible Party):

Maastricht University Medical Center

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Liver Lesions Requiring Hemihepatectomy	Procedure: Open or Laparoscopic left hemihepatectomy Procedure: Open or Laparoscopic right hemihepatectomy	Not Applicable

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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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	350 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Care Provider)
Masking Description:	The patient, surgical ward physician and surgical ward nurses are blinded up and until postoperative day 4.
Primary Purpose:	Treatment
Official Title:	The ORANGE II PLUS - Trial: an International Multicenter Randomized Controlled Trial of Open Versus Laparoscopic Hemihepatectomies.
Actual Study Start Date :	October 1, 2013
Actual Primary Completion Date :	December 4, 2019
Estimated Study Completion Date :	December 4, 2023

Arms and Interventions

Arm	Intervention/treatment
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.

Outcome Measures

Primary Outcome Measures :

Time to functional recovery [ Time Frame: expected average of 4-10 days ]
Time until a patient is functionally recovered

Secondary Outcome Measures :

Length of hospital stay [ Time Frame: 30 days ]
Total length of hospital stay
Readmission percentage [ Time Frame: 1 year ]
Total percentage of patients being readmitted
Total morbidity [ Time Frame: 1 year ]
Total morbidity during one year
Composite endpoint of liver specific morbidity [ Time Frame: 1 year ]
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 ]
Incidence of incisional hernia after 1 year
Quality of life: QLQ-C30 + LM 21 [ Time Frame: 1 year ]
Quality of life assessment (QLQ-C30 + LM 21) during one year
Body image and cosmesis [ Time Frame: 1 year ]
Influence of intervention on body image and cosmesis during one year
Reasons for delay in discharge after functional recovery [ Time Frame: 1 year ]
Intraoperative blood loss [ Time Frame: During procedure ]
Intraoperative time [ Time Frame: Surgical time from incision to closure ]
Resection margin [ Time Frame: During pathology assessment ]
Time to adjuvant chemotherapy initiation [ Time Frame: 1 year ]
Disease-free survival [ Time Frame: 1 year ]
Hospital and societal costs [ Time Frame: 1 year ]
Overall survival [ Time Frame: 1 year and 5 years ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01441856

Locations

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Belgium
Erasmus Hospital
Brussels, Belgium
Ghent University Hospital
Ghent, Belgium
Jessa Hospital
Hasselt, Belgium
General Hospital Groeninge
Kortrijk, Belgium
Germany
University Hospital Aachen
Aachen, Germany
Italy
San Raffaele Hospital
Milan, Italy
Netherlands
Academic Medical Center
Amsterdam, Netherlands
Maastricht University Medical Center+
Maastricht, Netherlands
Norway
University Hospital Oslo
Oslo, Norway
United Kingdom
Aintree University Hospital
Aintree, United Kingdom
Queen Elizabeth Hospital
Birmingham, United Kingdom
King's College Hospital
London, United Kingdom
Freeman Hospital
Newcastle, United Kingdom
Oxford University Hospitals
Oxford, United Kingdom
Derriford Hospital
Plymouth, United Kingdom
University Hospital Southampton
Southampton, United Kingdom

Sponsors and Collaborators