ORANGE SEGMENTS: Open Versus Laparoscopic Parenchymal Preserving Postero-Superior Liver Segment Resection

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ClinicalTrials.gov Identifier: NCT03270917

Recruitment Status : Recruiting

First Posted : September 1, 2017

Last Update Posted : February 21, 2020

See Contacts and Locations

Sponsor:

Collaborators:

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Queen Elizabeth Hospital Birmingham

General Hospital Groeninge

Liverpool University Hospitals NHS Foundation Trust

King's College Hospital NHS Trust

San Raffaele University Hospital, Italy

Newcastle-upon-Tyne Hospitals NHS Trust

Oslo University Hospital

Oxford University Hospitals NHS Trust

Derriford Hospital

University Hospital Southampton NHS Foundation Trust

Manchester University NHS Foundation Trust

University Hospital, Aachen

Erasme University Hospital

Moscow Clinical Scientific Center

San Camillo Hospital, Rome

Fondazione Poliambulanza Istituto Ospedaliero

Information provided by (Responsible Party):

Maastricht University Medical Center

Study Description

Brief Summary:

The international and multicentre ORANGE SEGMENTS - Trial is a prospective, double blinded, randomized controlled study comparing patients undergoing parenchymal preserving resection of postero-superior liver segments (involving one or two of segments 4a, 7, 8). All patients will be participating in an enhanced recovery programme.

Primary outcome is time to functional recovery. Secondary study parameters include hospital length of stay, intraoperative blood loss, operation time, liver specific morbidity, readmission percentage, resection margin, quality of life, body image and cosmesis , reasons for delay of discharge after functional recovery, long term incidence of incisional hernias, hospital and societal costs during one year, time to adjuvant chemotherapy initiation, overall five-year survival.

Condition or disease	Intervention/treatment	Phase
Liver Surgery	Procedure: Parenchymal preserving postero-superior liver segment resection	Not Applicable

Show detailed description

Detailed Description:

Liver resection for colorectal metastasis is a potential curative therapy and has become the standard of care in appropriately staged patients, offering five-year survival rates ranging from 38 up to 61% in selected cases, with approximately 30% of patients surviving ten years or more, compared to five-year survival rates of less than 5% for patients not amenable to resection. Liver surgery is also a widely accepted treatment for symptomatic benign lesions and those of uncertain nature or large size. Whilst the figures are a vast improvement on the past, there is still a need to refine the treatment of these patients, including surgical technique.

Open hepatectomy is the current standard of care for the management of primary and secondary tumours. The open postero-superior liver segment resection requires a large incision to achieve adequate access and proper control during resection. This has a significant impact on patient's recovery and, in cases of small resections, this access may represent the major component of surgical trauma. Advances in surgical technique and expertise now permit these operations to be performed with minor incisions by using the laparoscopic approach. Although the feasibility of laparoscopic hepatectomy has been established, only select centres use this technique as their primary modality.

Laparoscopic liver resection was first reported in 1991. Over the past decades, the method has gained wide acceptance for various liver resection procedures. Multiple retrospective case series, patient cohorts, systematic reviews and meta-analyses have compared open with laparoscopic liver surgery and indicate the laparoscopic approach to be safely applicable for the resection of 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 and earlier recovery. Despite this, concerns remain over operative times, the ability to control haemorrhage laparascopically and long-term oncological outcomes.

Initially, the left lateral segments of the liver were chosen for anatomic laparoscopic resection, with good results. Many liver centres worldwide currently use laparoscopy for resection of the anterior liver segments. Whilst case control studies would now seem sufficient to allay such concerns in the context of minor liver resections and left lateral sectionectomies, the adoption and dissemination of laparoscopy by hepatobiliary oncologic surgeons for major hepatectomies and resections of postero-superior segments has been restricted. Besides the relatively low volume of patients, major laparoscopic liver resections are technically demanding, have a significant learning curve, are time consuming, are thought to hold an increased morbidity risk and lack in evidence.

Nevertheless, a new impulse for the laparoscopic management of major liver lesions came after the first reports of laparoscopic hemihepatectomies, which demonstrated that in expert hands major anatomical laparoscopic liver resections are feasible with good efficacy and safety. When comparing surgical procedures, one of the easiest to measure and often used outcomes is the length of hospital stay; the time it takes for a patient to be discharged from the hospital after an operation. On the whole, a median hospital length of stay of 6.0 to 13.1 days and 3.5 to 10.0 days have been observed after open and laparoscopic hepatic resections in European centres respectively. For major surgery in expert centres, median duration of hospital admission varied between 6 to 12.5 days for open surgery and 4 to 8.2 days for laparoscopic resections. Concentrating on postero-superior liver segment resections, the median hospital stay is 6 days (3-44 days) for those undergoing open compared with 4 days (1-11 days) for those having laparoscopic resections.

Besides the immediate benefits to the patient, such as decreased intraoperative blood loss, diminished postoperative pain, earlier recovery and reduced hospital length of stay, laparoscopic liver surgery may also have the potential to improve outcomes in the longer term by reducing complications, enhancing quality of life, improving cosmesis, ensuring early commencement and completion of adjuvant therapies. However, level-1 evidence on all outcomes is still to be presented.

Within the framework of optimized perioperative care, broader indications for hepatic surgery and further adoption of laparoscopic liver resections, there is a clear need for a randomized trial. Therefore, the multicentre and international ORANGE SEGMENTS - Trial has been designed to provide evidence on the merits of laparoscopic versus open parenchymal preserving postero-superior liver segment resection within an enhanced recovery programme 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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	250 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Intervention Model Description:	Patients will be randomised to either the open or the laparoscopic treatment arm.
Masking:	Double (Participant, Investigator)
Masking Description:	The patient, ward physician and research investigator are blinded to the treatment intervention. A large abdominal dressing will be used to cover the incision(s) until postoperative day 4. Obviously, the surgeon and anaesthesiology team can not be blinded.
Primary Purpose:	Treatment
Official Title:	The ORANGE SEGMENTS - Trial: an International Multicentre Randomized Controlled Trial of Open Versus Laparoscopic Parenchymal Preserving Postero-superior Liver Segment Resection
Actual Study Start Date :	November 1, 2017
Estimated Primary Completion Date :	April 30, 2021
Estimated Study Completion Date :	December 31, 2024

Arms and Interventions

Arm	Intervention/treatment
Open Open liver surgery	Procedure: Parenchymal preserving postero-superior liver segment resection Parenchymal preserving liver segment resection of one or two of the postero-superior liver segments (4A, 7 or 8).
Laparoscopy Laparoscopic liver surgery	Procedure: Parenchymal preserving postero-superior liver segment resection Parenchymal preserving liver segment resection of one or two of the postero-superior liver segments (4A, 7 or 8).

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 :

Hospital length of stay [ Time Frame: 30 days ]
Total length of hospital stay
Intraoperative blood loss [ Time Frame: during procedure ]
Net intraoperative blood loss
Operating time [ Time Frame: surgical time from incision until closure ]
(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)
Readmission percentage [ Time Frame: 1 year ]
Total percentage of patients being readmitted
Resection margin [ Time Frame: 1 year ]
Residual tumor cells in resection border
Quality of life [ Time Frame: 1 year ]
The physical, social and emotional well-being of the patient
Body image and cosmesis [ Time Frame: 1 year ]
The aesthetic appearance of the scars associated with the operation and its influence on the patient self-view
Reasons for delay of discharge after functional recovery [ Time Frame: 1 year ]
All reasons that may cause delay in discharge after the patient has recovered functionally, such as administrative reasons, patient confidence, logistics problems, etc.
Incisional herniation [ Time Frame: 1 year ]
Cicatricial hernia
Hospital and societal costs [ Time Frame: 1 year ]
All costs that are associated with the operation, including in-hospital costs and out of hospital costs, such as home care, work absence, etc.
Time to adjuvant chemotherapy initiation [ Time Frame: 1 year ]
The time it takes to start adjuvant chemotherapy after the patient has been operated
Overall five-year survival [ Time Frame: 5 years ]
Five-year survival

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 a parenchymal sparing liver resection (including wedge resections and full segmentectomies) involving one or two of segments 4a/7/8 for accepted indications . A segment 6/7 resection would also be eligible.
Able to understand the nature of the study and what will be required of them.
Men and non-pregnant, non-lactating women, aged 18 years and older.
BMI between and including 18-35 kg/m2
Patients with ASA physical status I-II-III.

Exclusion Criteria:

Inability to give (written) informed consent.
Patients requiring other liver surgery than a parenchymal sparing resection involving one or two of segments 4a, 7, 8.
Patients requiring parenchymal sparing liver resection involving segment 1. This is due to the high level of technical difficulty.
Patients with hepatic lesion(s), that are located with insufficient margin from vascular or biliary structures to be operated laparoscopically.
Patients with ASA physical status 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): NCT03270917

Contacts

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Contact: Christoph Kummerli, MD	‭+41763875744‬	c.kummerli@soton.ac.uk
Contact: Zina Eminton	+447973551272	z.b.eminton@soton.ac.uk

Locations

Show 18 study locations

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Belgium
Erasmus Hospital	Not yet recruiting
Brussels, Belgium
Contact: V. Lucidi, MD PhD
Principal Investigator: V. Lucidi, MD PhD
Sub-Investigator: G. Katsanos, MD PhD
General Hospital Groeninge	Recruiting
Kortrijk, Belgium
Contact: M. D'Hondt, MD PhD
Principal Investigator: M. D'Hondt, MD PhD
Germany
University Hospital Aachen	Not yet recruiting
Aachen, Germany
Contact: U.P. Neumann, Prof.
Principal Investigator: U.P. Neumann, Prof.
Sub-Investigator: F. Ulmer, MD PhD
Italy
Poliambulanza Hospital	Recruiting
Brescia, Italy
Contact: M. Abu Hilal, Prof.
Principal Investigator: M. Abu Hilal, Prof.
Sub-Investigator: G. Zimmitti, MD PhD
San Raffaele Hospital	Recruiting
Milan, Italy
Contact: L. Aldrighetti, Prof.
Principal Investigator: L. Aldrighetti, Prof.
Sub-Investigator: F. Ratti, MD PhD
San Camillo-Forlanini Hospital	Recruiting
Rome, Italy
Contact: G.M. Ettore, MD PhD
Principal Investigator: G.M. Ettore, MD PhD
Sub-Investigator: S. Ferretti, MD PhD
Netherlands
Academic Medical Center	Recruiting
Amsterdam, Netherlands
Contact: M.G. Besselink, MD PhD
Principal Investigator: M.G. Besselink, MD PhD
Maastricht University Medical Center+	Not yet recruiting
Maastricht, Netherlands
Contact: R.M. van Dam, MD PhD
Principal Investigator: R.M. van Dam, MD PhD
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
Russian Federation
Moscow Clinical Scientific Center	Recruiting
Moscow, Russian Federation
Contact: M. Efanov, Prof.
Principal Investigator: M. Efanov, Prof.
Sub-Investigator: A. Chitadze, MD PhD
United Kingdom
Aintree University Hospital	Recruiting
Aintree, United Kingdom
Contact: v Díaz-Nieto, MD PhD
Principal Investigator: R. Díaz-Nieto, MD PhD
Queen Elizabeth Hospital	Recruiting
Birmingham, United Kingdom
Contact: R. Sutcliffe, MD PhD
Principal Investigator: R. Sutcliffe
Sub-Investigator: P. Marudanayagam
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
Manchester Royal Infirmary	Recruiting
Manchester, United Kingdom
Contact: A.J. Sheen, Prof.
Principal Investigator: A.J. Sheen, Prof.
Sub-Investigator: J.J. Pilkington, MD PhD
Freeman Hospital	Recruiting
Newcastle, United Kingdom
Contact: S. White, Prof.
Principal Investigator: S. White, Prof.
Sub-Investigator: S. Robinson, MD PhD
Oxford University Hospitals	Not yet recruiting
Oxford, United Kingdom
Contact: Z. Soonawalla, MD PhD
Principal Investigator: Z. Soonawalla, MD PhD
Sub-Investigator: M.A. Silva, 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: M. Halls, MD PhD
Principal Investigator: M. Abu Hilal, Prof.
Principal Investigator: J. Primrose, Prof.
Sub-Investigator: M. Halls, MD PhD
Sub-Investigator: S. Pugh, 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

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Queen Elizabeth Hospital Birmingham

General Hospital Groeninge

Liverpool University Hospitals NHS Foundation Trust

King's College Hospital NHS Trust

San Raffaele University Hospital, Italy

Newcastle-upon-Tyne Hospitals NHS Trust

Oslo University Hospital

Oxford University Hospitals NHS Trust

Derriford Hospital

University Hospital Southampton NHS Foundation Trust

Manchester University NHS Foundation Trust

University Hospital, Aachen

Erasme University Hospital

Moscow Clinical Scientific Center

San Camillo Hospital, Rome

Fondazione Poliambulanza Istituto Ospedaliero

Investigators

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Study Chair:	Mohammed Abu Hilal, Prof.	University Hospital Southampton NHS Foundation Trust
Study Chair:	John Primrose, Prof.	University Hospital Southampton NHS Foundation Trust

More Information

Additional Information:

The ORANGE - Trials consortium webpage This link exits the ClinicalTrials.gov site

Publications:

Coles SR, Besselink MG, Serin KR, Alsaati H, Di Gioia P, Samim M, Pearce NW, Abu Hilal M. Total laparoscopic management of lesions involving liver segment 7. Surg Endosc. 2015 Nov;29(11):3190-5. doi: 10.1007/s00464-014-4052-2. Epub 2015 Jan 13.

Cipriani F, Shelat VG, Rawashdeh M, Francone E, Aldrighetti L, Takhar A, Armstrong T, Pearce NW, Abu Hilal M. Laparoscopic Parenchymal-Sparing Resections for Nonperipheral Liver Lesions, the Diamond Technique: Technical Aspects, Clinical Outcomes, and Oncologic Efficiency. J Am Coll Surg. 2015 Aug;221(2):265-72. doi: 10.1016/j.jamcollsurg.2015.03.029. Epub 2015 Mar 27.

Scuderi V, Barkhatov L, Montalti R, Ratti F, Cipriani F, Pardo F, Tranchart H, Dagher I, Rotellar F, Abu Hilal M, Edwin B, Vivarelli M, Aldrighetti L, Troisi RI. Outcome after laparoscopic and open resections of posterosuperior segments of the liver. Br J Surg. 2017 May;104(6):751-759. doi: 10.1002/bjs.10489. Epub 2017 Feb 13.

Zheng B, Zhao R, Li X, Li B. Comparison of laparoscopic liver resection for lesions located in anterolateral and posterosuperior segments: a meta-analysis. Surg Endosc. 2017 Nov;31(11):4641-4648. doi: 10.1007/s00464-017-5527-8. Epub 2017 Apr 7.

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Responsible Party:	Maastricht University Medical Center
ClinicalTrials.gov Identifier:	NCT03270917
Other Study ID Numbers:	NL36215.068.11*
First Posted:	September 1, 2017 Key Record Dates
Last Update Posted:	February 21, 2020
Last Verified:	February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Maastricht University Medical Center:


Parenchymal preserving Postero-superior Laparoscopy Hepatectomy

Additional relevant MeSH terms:

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Liver Extracts Hematinics

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