The ORANGE II PLUS - Trial: Open Versus Laparoscopic Hemihepatectomy

Liver Lesions Requiring Hemihepatectomy Clinical Trial

Official title:

The ORANGE II PLUS - Trial: an International Multicenter Randomized Controlled Trial of Open Versus Laparoscopic Hemihepatectomies.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01441856
• Other study ID #: NL36215.068.11
• Status: Active, not recruiting
• Phase: N/A
• Start date: October 1, 2013
• Est. completion date: December 4, 2023

Study information

• Verified date: March 2021
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 350
• Est. completion date: December 4, 2023
• Est. primary completion date: December 4, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Liver Lesions Requiring Hemihepatectomy

Intervention

Procedure:
• Open or Laparoscopic left hemihepatectomy
Patients in this arm will undergo a left hemihepatectomy within an Enhanced Recovery After Surgery Program.
• Open or Laparoscopic right hemihepatectomy
Patients in this arm will undergo a right hemihepatectomy within an Enhanced Recovery After Surgery Program.

Locations

Country	Name	City	State
Belgium	Erasmus Hospital	Brussels
Belgium	Ghent University Hospital	Ghent
Belgium	Jessa Hospital	Hasselt
Belgium	General Hospital Groeninge	Kortrijk
Germany	University Hospital Aachen	Aachen
Italy	San Raffaele Hospital	Milan
Netherlands	Academic Medical Center	Amsterdam
Netherlands	Maastricht University Medical Center+	Maastricht
Norway	University Hospital Oslo	Oslo
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

Sponsors (16)

Lead Sponsor

Collaborator

Maastricht University Medical Center

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Derriford Hospital, General Hospital Groeninge, Jessa Hospital, King's College London, Liverpool University Hospitals NHS Foundation Trust, Newcastle-upon-Tyne Hospitals NHS Trust, Oslo University Hospital, Oxford University Hospitals NHS Trust, Queen Elizabeth Hospital NHS Foundation Trust, San Raffaele University Hospital, Italy, Universitair Ziekenhuis Brussel, University Hospital Southampton NHS Foundation Trust, University Hospital, Aachen, University Hospital, Ghent

Countries where clinical trial is conducted

Belgium,  Germany,  Italy,  Netherlands,  Norway,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to functional recovery	Time until a patient is functionally recovered	expected average of 4-10 days
Secondary	Length of hospital stay	Total length of hospital stay	30 days
Secondary	Readmission percentage	Total percentage of patients being readmitted	1 year
Secondary	Total morbidity	Total morbidity during one year	1 year
Secondary	Composite endpoint of liver specific morbidity	Composite endpoint of liver specific morbidity(intra-abdominal bleeding, intra-abdominal abcess, ascites, postresectional liver failure, intra-operative mortality, bile leakage)	1 year
Secondary	Long term incidence of incisional hernia	Incidence of incisional hernia after 1 year	1 year
Secondary	Quality of life: QLQ-C30 + LM 21	Quality of life assessment (QLQ-C30 + LM 21) during one year	1 year
Secondary	Body image and cosmesis	Influence of intervention on body image and cosmesis during one year	1 year
Secondary	Reasons for delay in discharge after functional recovery		1 year
Secondary	Intraoperative blood loss		During procedure
Secondary	Intraoperative time		Surgical time from incision to closure
Secondary	Resection margin		During pathology assessment
Secondary	Time to adjuvant chemotherapy initiation		1 year
Secondary	Disease-free survival		1 year
Secondary	Hospital and societal costs		1 year
Secondary	Overall survival		1 year and 5 years