Regeneration of Liver: Portal Vein Embolization Versus Radiofrequency Assisted Ligation for Liver Hypertrophy (REBIRTH) (REBIRTH)

Liver Regeneration: a Single-centre, Prospective, Randomised Controlled Trial Comparing Radiofrequency Assisted Liver Partition With Portal Vein Ligation (RALPP) With Portal Vein Embolization (PVE) for Preoperative Induction of Liver Hypertrophy in Patients With Insufficient Future Liver Remnant Volume for Major Liver Resection.

The aim of this study is to compare two different techniques (portal vein embolization and radiofrequency assisted liver partition with portal vein ligation) for increasing liver volume prior to major liver resection.

Study Overview

• Status: Completed
• Conditions: Cancer; Liver Resection
• Intervention / Treatment: Procedure: Portal vein embolization (PVE); Procedure: Radiofrequency assisted liver partition with portal vein ligation (RALPP)

Detailed Description

Liver resection remains the gold standard treatment for patients with liver tumours providing them the only chance for long-term survival. In up to 45% of cases that are amenable to surgical resection, an extended hepatectomy (removal of part of the liver) is usually necessary to achieve a clear resection margin. However, there must be enough liver left behind to meet the demands of the body. Indeed, liver failure due to insufficient remnant liver volume is still the principal cause of postoperative death following a major liver resection.

The liver receives its main blood supply from two vessels (the portal vein and the hepatic artery). In order to decrease the complications and improve the safety of extensive liver surgery in patients with insufficient future liver remnant volume (FLRV), pre-operative embolization (i.e. blockage) of part of the portal vein can be undertaken.

This has the effect of inducing growth of the liver on the unaffected side. Thus, when the resection is carried out, an increased FLRV (of around 12%) reduces post-operative liver failure. An alternative technique is to perform surgical ligation of the portal vein along with splitting of the liver.

The diseased portion of liver is left in the body for 7-10 days while the healthy side is induced to grow. During this time, the diseased portion continues to support the body's requirement for liver function and reduces the risk of liver failure. FLRV has been shown to increase by around 74% with this technique.

However, there are more postoperative complications with the alternative technique such as bile leaks. The aim of this study is to test a new way of splitting the liver so that the increased FLRV can be achieved without the increased complication rate.

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W12 0HS
    • Hammersmith Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 years
• Any patient requiring right or extended right hepatectomy with FLRV less than 25% on preoperative volumetric study
• WHO performance status 0, 1 or 2
• Patient able to comply with protocol requirements and deemed fit for surgical resection
• Written informed consent

Exclusion Criteria:

• Inability to give informed consent
• Pregnancy
• WHO status 3 or 4
• New York Heart Association Classification Grade III or IV

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Portal vein embolization (PVE); Patients allocated to the PVE group will receive pre-intervention blood tests and a contrast enhanced CT scan of the abdomen. They will then have their portal vein embolized radiologically once their pre-intervention investigations have been completed and reviewed by the clinical team. Post-intervention investigations (blood tests and CT scan) will take place 4 weeks after the completion of the PVE. At this point, they will be listed to receive their definitive surgical hepatectomy.	Procedure: Portal vein embolization (PVE)
Experimental: Radiofrequency assisted liver partition and ligation (RALPP); Patients allocated to the RALPP group will receive pre-intervention blood tests and a contrast enhanced CT scan of the abdomen. They will then have their right portal vein surgically ligated followed by radiofrequency ablation in situ splitting of the liver. Certain patients may additionally have a tumourectomy or wedge resection of the left liver lobe if clinically indicated. The RALPP procedure will occur once the patient's pre-intervention investigations have been completed and reviewed by the clinical team. Post-intervention investigations (blood tests and CT scan) will take place 2 weeks after the completion of the RALPP. At this point, they will be listed to receive their definitive surgical hepatectomy.	Procedure: Radiofrequency assisted liver partition with portal vein ligation (RALPP)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Liver Remnant Volume	Percentage change in remnant liver volume following intervention. This will be measured by volumetric analysis of CT scan. Positive number represents increases and negative number represents decreases.	2 or 4 weeks post intervention (2 weeks post RALPP; 4 weeks post PVE)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Liver Function Tests	Blood tests	Postoperatively (daily until discharge; then at clinic appointments up to 18 months from randomization)
Number of Participants With Postoperative Complications (Dindo Clavien ≥Grade 3b)	As defined by Dindo Clavien classification of surgical complications (≥grade 3b).	Up to hospital discharge (estimated to be between 2 and 10 days)

Collaborators and Investigators

• Sponsor: Imperial College London
• Investigators: Principal Investigator: Long R Jiao, MD, FRCS, Imperial College London

Publications and helpful links

General Publications

• Gall TM, Sodergren MH, Frampton AE, Fan R, Spalding DR, Habib NA, Pai M, Jackson JE, Tait P, Jiao LR. Radio-frequency-assisted Liver Partition with Portal vein ligation (RALPP) for liver regeneration. Ann Surg. 2015 Feb;261(2):e45-6. doi: 10.1097/SLA.0000000000000607. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2015
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: August 5, 2014
• First Submitted That Met QC Criteria: August 13, 2014
• First Posted (Estimate): August 15, 2014

Study Record Updates

• Last Update Posted (Actual): November 7, 2019
• Last Update Submitted That Met QC Criteria: October 18, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Liver resection; Liver metastases; Portal vein embolization; Liver hypertrophy; Portal vein ligation; Radiofrequency splitting
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Hypertrophy
• Other Study ID Numbers: 14/LO/1123

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No