HepaRAS Trial: Changes in Hepatectomy Risk Assessment When Using Mebrofenin HIDA (HepaRAS)

HepaRAS Trial: Changes in Hepatectomy Risk Assessment When Incorporating Mebrofenin HIDA for Functional Evaluation of the Liver Remnant: A Pilot Study

Surgical procedures to remove a significant portion of the liver are used to treat various diseases including cancer. They have demonstrated to be the most effective treatment for selected patients. These procedures rely on the fascinating ability of the liver to grow back, allowing surgeons to remove of up to 70% of the organ in a safe manner. However, there are instances where severe complications and death occur due to the inability of the residual liver to perform all functions. It is estimated that up to 32% of patients undergoing this type of surgery will experience such complications. To prevent this, physicians calculate the total liver volume before surgery using radiology and estimate how much liver will remain after surgery. Only when the liver remnant is 30% or higher, the procedure is deemed safe.

One of the main limitations of this strategy is that the estimated percentage of the liver remnant does not entirely reflect a proportional function. To overcome this limitation and avoid serious complications, a more precise assessment is required. Recently, a new scan was introduced using mebrofenin, which is metabolized in the liver and can be traced in a particular region of the organ using computer software. As a result, clinicians can know with certainty, the percentual function of a portion of the liver, and if that portion will be sufficient to avoid complications and death after a major liver operation.

This project proposes incorporating this technology for preoperative evaluation against our traditional assessment using just volume calculations. Participants will be randomly assigned to the traditional volume calculation or the new scan with mebrofenin, and investigators will compare how well both methods are able to predict complications and death after surgery. Researchers are particularly interested in demonstrating if major complications and death after surgery are less using the new mebrofenin scan.

Our study evaluating the introduction of a new and relatively harmful technique will help to better identify those patients with high risk for complications and death after a major surgical procedure on the liver. This will help in better selecting future patients and will allow for a more precise discussion during initial evaluation.

Study Overview

• Status: Withdrawn
• Conditions: Liver Failure as A Complication of Care; 30-day Mortality
• Intervention / Treatment: Diagnostic test: mHBS; Diagnostic test: CT/MRI volumetry

Detailed Description

Surgical procedures to remove a significant portion of the liver are used to treat various diseases, including cancer. They have been demonstrated to be the most effective treatment for selected patients. These procedures rely on the fascinating ability of the liver to grow back, allowing surgeons to remove up to 70% of the organ in a safe manner. However, there are instances where severe complications and death occur due to the inability of the residual liver to perform all functions. It is estimated that up to 32% of patients undergoing this type of surgery will experience such complications. To prevent this, physicians use radiology to calculate the total liver volume before surgery and estimate how much liver will remain after surgery. The procedure is deemed safe only when the liver remnant is 30% or higher.

One of the main limitations of this strategy is that the estimated percentage of the liver remnant does not entirely reflect a proportional function. A more precise assessment is required to overcome this limitation and avoid serious complications. Recently, a new scan was introduced using computer software using mebrofenin, which is metabolized in the liver and can be traced in a particular organ region. As a result, clinicians can know with certainty the percentual function of a portion of the liver and if that portion will be sufficient to avoid complications and death after a major liver operation.

This project proposes incorporating this technology for preoperative evaluation against our traditional assessment using just volume calculations. Participants will be randomly assigned to the traditional volume calculation or the new scan with mebrofenin, and investigators will compare how well both methods are able to predict complications and death after surgery. Researchers are particularly interested in demonstrating if major complications and death after surgery are less common using the new mebrofenin scan.

Our study evaluating the introduction of a new and relatively harmful technique will help to better identify those patients with a high risk for complications and death after a major surgical procedure on the liver. This will help better select future patients and allow for a more precise discussion during the initial evaluation.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Boris Gala-Lopez; Phone Number: 1 (902) 473 - 7411; Email: b.gala-lopez@dal.ca

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• All adult patients who are being considered for major hepatectomy at the QEII and McGill for malignant or benign disease.
• Both open and laparoscopic approaches will be accepted in the study.
• Patients with underlying liver cirrhosis or receiving additional ablation therapies will not be excluded.

Exclusion Criteria:

• Patients younger than 18 years-old.
• Pregnant patients.
• Hepatectomy is associated with another major non-liver procedure.
• Patients not qualifying for a major hepatectomy following preoperative assessment.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Future Liver Remnant Function (FLRF); Preoperative FLRF risk assessment via 99mTc-mebrofenin hepatobiliary scintigraphy (mHBS)	Diagnostic test: mHBS; Preoperative FLRF assessment using 99mTc-mebrofenin hepatobiliary scintigraphy (mHBS).
Active Comparator: Future Liver Remnant Volume (FLRV); Preoperative FLRV assessment by CT/MRI volumetry	Diagnostic test: CT/MRI volumetry; Preoperative FLRF assessment using CT/MRI volumetry

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with post-hepatectomy liver failure (PHLF)	Incidence of post-hepatectomy liver failure (PHLF)	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital length of stay	Hospital length of stay	30 days
30-day mortality	30-day mortality	30 days
Number of participants with the 50-50 criteria	Prothrombin time <50% of normal and serum bilirubin >50 µmol/L on POD 5, which is an early predictor of more than 50% mortality rate after hepatectomy.	5 days
Number of participants with major postoperative complications as per Clavien-Dindo classification	Occurrence of major postoperative complications as per Clavien-Dindo classification	30 days

Collaborators and Investigators

• Sponsor: Boris Gala Lopez
• Collaborators: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Investigators: Principal Investigator: Boris Gala-Lopez, MD, MSC, PhD, Queen Elizabeth II Health Sciences Centre. Dalhousie University

Publications and helpful links

General Publications

• de Graaf W, van Lienden KP, Dinant S, Roelofs JJ, Busch OR, Gouma DJ, Bennink RJ, van Gulik TM. Assessment of future remnant liver function using hepatobiliary scintigraphy in patients undergoing major liver resection. J Gastrointest Surg. 2010 Feb;14(2):369-78. doi: 10.1007/s11605-009-1085-2.
• Guglielmi A, Ruzzenente A, Conci S, Valdegamberi A, Iacono C. How much remnant is enough in liver resection? Dig Surg. 2012;29(1):6-17. doi: 10.1159/000335713. Epub 2012 Mar 15.
• Gupta M, Choudhury PS, Singh S, Hazarika D. Liver Functional Volumetry by Tc-99m Mebrofenin Hepatobiliary Scintigraphy before Major Liver Resection: A Game Changer. Indian J Nucl Med. 2018 Oct-Dec;33(4):277-283. doi: 10.4103/ijnm.IJNM_72_18.
• Bennink RJ, Dinant S, Erdogan D, Heijnen BH, Straatsburg IH, van Vliet AK, van Gulik TM. Preoperative assessment of postoperative remnant liver function using hepatobiliary scintigraphy. J Nucl Med. 2004 Jun;45(6):965-71.

Study record dates

Study Major Dates

• Study Start (Estimated): January 15, 2023
• Primary Completion (Estimated): February 28, 2025
• Study Completion (Estimated): July 30, 2025

Study Registration Dates

• First Submitted: March 6, 2022
• First Submitted That Met QC Criteria: March 14, 2022
• First Posted (Actual): March 15, 2022

Study Record Updates

• Last Update Posted (Estimated): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Hepatic Insufficiency; Liver Diseases; Liver Failure
• Other Study ID Numbers: 45465

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