Surgical Recovery After Left Lateral Hepatic Sectionectomy: Laparoscopic Versus Open Surgery. (ORANGE II)

The ORANGE II Trial: An International Multicenter Randomised Controlled Trial of Optimised Surgical Recovery After Left Lateral Hepatic Sectionectomy: Open Versus Laparoscopic Surgery Within an Enhanced Recovery Programme

The ORANGE II trial is a double blinded randomised controlled trial that will provide evidence on the merits of laparoscopic surgery in patients undergoing a left lateral hepatic sectionectomy in terms of time to functional recovery, hospital length of stay, quality of life, readmission percentage, morbidity and mortality, hospital costs, body image and cosmesis, and long term incidence of incisional hernias.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Liver Disease; Liver Metastasis
• Intervention / Treatment: Procedure: open left lateral hepatic sectionectomy; Procedure: laparoscopic left lateral hepatic sectionectomy

Detailed Description

Recent developments in liver surgery include the introduction of laparoscopic surgery and enhanced recovery programmes. Laparoscopic surgery and enhanced recovery programmes both focus on faster recovery and consequently shorter hospital length of stay.

The ORANGE-II trial is a prospective randomised controlled parallel group superiority trial with a double-blinded experimental and a prospective registry design to determine whether laparoscopic surgery is to be preferred over open surgery in patients undergoing a left lateral hepatic sectionectomy within an enhanced recovery programme. The experimental design produces two randomised arms; (a) open LLS and (b) laparoscopic LLS. An additional registry arm will be based on surgeons/patients that do not want to be randomised because they have an explicit preference for either the laparoscopic LLS or for the open LLS (c).

The primary endpoint of the ORANGE II trial is time to functional recovery. The functional recovery criteria consist of adequate pain control with oral analgetics only, mobility restored to an independent level, absence of intravenous fluid administration, ability to eat solid foods and finally a normal or decreasing serum bilirubin level. A patient is fully functionally recovered when all of the five criteria are satisfied.

Secondary endpoints of this trial are postoperative length of hospital stay, readmission percentage, (liver specific) morbidity, quality of life, body image and cosmetic result, hospital and societal costs during one year and long-term incidence of incisional hernias.

The ORANGE-II trial is a randomised controlled multicentre trial that will provide evidence on the merits of laparoscopic surgery in patients undergoing a left lateral hepatic sectionectomy and participating in an enhanced recovery programme.

• Study Type: Interventional
• Enrollment (Anticipated): 110
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6202 AZ
      • Maastricht University Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients suitable for undergoing both laparoscopic left lateral sectionectomy as well as open left lateral sectionectomy of the liver.
• Able to understand the nature of the study and what will be required of them.
• Men and non-pregnant, non-lactating women between age 18-80.
• 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 lateral hepatic sectionectomy.
• Patients with ASA IV-V
• Underlying liver disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; patients undergoing open left lateral hepatic sectionectomy	Procedure: open left lateral hepatic sectionectomy; open left lateral hepatic sectionectomy
Active Comparator: 2; patients undergoing a laparoscopic left lateral hepatic sectionectomy	Procedure: laparoscopic left lateral hepatic sectionectomy; laparoscopic left lateral hepatic sectionectomy
Active Comparator: 3; Prospective registry of patients that cannot be randomized (both open and laparoscopic left lateral hepatic sectionectomy)	Procedure: open left lateral hepatic sectionectomy; open left lateral hepatic sectionectomy; Procedure: laparoscopic left lateral hepatic sectionectomy; laparoscopic left lateral hepatic sectionectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to functional Recovery	The functional recovery criteria consist of adequate pain control with oral analgetics only, mobility restored to an independent level, absence of intravenous fluid administration, ability to eat solid foods and finally a normal or decreasing serum bilirubin level. A patient is fully functionally recovered when all of the five criteria are satisfied. It is medically justified to discharge patients when the criteria for full functional recovery are met and if the patient is willing to go home.	Date the functional recovery criteria are met

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative length of hospital stay	including readmission <30 days	30 days
Readmission percentage	Readmission percentage during one year follow-up	1 year
Total morbidity	Morbidity will be classified and analysed according to the validated classification for postoperative morbidity as described by Dindo et al.	1 year
Composite endpoint of liver surgery specific morbidity	Parameter composed of a combination of procedure-specific complications and considered as a single, dichotomous outcome: operative mortality, intra-abdominal haemorrhage, ascites, bile leakage, intra-abdominal abscess and postresectional liver failure. These components, which are all specific to liver surgery and have substantial clinical relevance, reflect Dindo grade 3-5 complications. A composite score of 1 (=failure) will reflect the occurrence of at least one of the above liver specific complications, consequently a score of 0 (=success) will be assigned if none occur.	1 year
Quality of life	To assess quality of life the Dutch version of the EQ-5D (EuroQol Group) status test in Dutch centres and the translated EQ-5D for international centres will be used. Furthermore, the EORTC QLQ-C30 with the LM21 module will be used for liver specific treatment measurements. Assessment of the patients' quality of life will be performed at the time of consent, discharge and 10 days, 3, 6 and 12 months after discharge.	1 year
Body image and cosmesis	To evaluate differences in postoperative body image and cosmesis, the Body image Questionnaire (BIQ) will be used. The BIQ consists of 8 questions regarding body image and cosmesis. The body image assessment will be performed preoperatively at time of consent. Both the body image and the cosmesis assessment will take place at discharge, 10 days, 3 months, 6 months and 12 months after discharge	1 year
Hospital and societal costs	The economic evaluation will include a cost-utility analysis from a Dutch societal perspective. The incremental costs per Quality Adjusted Life Year (QALY) gained will be based on utility scores from the EQ-5D. All hospital expenses (direct and indirect) related to both interventions will be monitored. In addition, a cost questionnaire offered at the regular follow-up consultation (3, 6 and 12 months) will help us to assess the societal and individual costs outside health care relating to patients' absence, impaired mobility, work or normal daily activities.	1 year
Incidence of incisional hernias	To assess the incidence of incisional hernias in laparoscopic and open left lateral hepatic sectionectomy patients will be contacted at a mean time of 1 year after resection to receive an ultrasound to diagnose incisional hernia.	1 year
Reasons for delay of discharge after functional recovery	Factors delaying discharge after functional recovery will be monitored.	untill Discharge

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: University Medical Center Groningen; UMC Utrecht; Erasmus Medical Center; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Maxima Medical Center; Onze Lieve Vrouwe Gasthuis; Deventer Ziekenhuis; Isala; University Medical Center Nijmegen; University Hospital, Aachen; San Raffaele University Hospital, Italy; Medisch Spectrum Twente
• Investigators: Principal Investigator: Cornelis HC Dejong, MD, PhD, Maastricht University Medical Centre; Study Director: Ronald M van Dam, MD, Maastricht University Medical Centre

Publications and helpful links

General Publications

• Wong-Lun-Hing EM, van Dam RM, van Breukelen GJ, Tanis PJ, Ratti F, van Hillegersberg R, Slooter GD, de Wilt JH, Liem MS, de Boer MT, Klaase JM, Neumann UP, Aldrighetti LA, Dejong CH; ORANGE II Collaborative Group. Randomized clinical trial of open versus laparoscopic left lateral hepatic sectionectomy within an enhanced recovery after surgery programme (ORANGE II study). Br J Surg. 2017 Apr;104(5):525-535. doi: 10.1002/bjs.10438. Epub 2017 Jan 31.
• van Dam RM, Wong-Lun-Hing EM, van Breukelen GJ, Stoot JH, van der Vorst JR, Bemelmans MH, Olde Damink SW, Lassen K, Dejong CH; ORANGE II Study Group. Open versus laparoscopic left lateral hepatic sectionectomy within an enhanced recovery ERAS(R) programme (ORANGE II-trial): study protocol for a randomised controlled trial. Trials. 2012 May 6;13:54. doi: 10.1186/1745-6215-13-54.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: March 31, 2009
• First Submitted That Met QC Criteria: April 1, 2009
• First Posted (Estimate): April 2, 2009

Study Record Updates

• Last Update Posted (Estimate): March 9, 2016
• Last Update Submitted That Met QC Criteria: March 8, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Colorectal cancer liver metastasis; Benign liver disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Liver Diseases; Colorectal Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: MEC 08-2-110