HepaRAS TRIAL: CHANGES IN HEPATECTOMY RISK ASSESSMENT WHEN INCORPORATING MEBROFENIN HIDA

Study Overview
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Brief Summary
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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, we 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 we will compare how well both methods are able to predict complications and death after surgery. We 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.

Official Title
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HepaRAS TRIAL: CHANGES IN HEPATECTOMY RISK ASSESSMENT WHEN INCORPORATING MEBROFENIN HIDA FOR FUNCTIONAL EVALUATION OF THE LIVER REMNANT: A PILOT STUDY

Conditions
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Liver Failure as A Complication of Care, 30-day Mortality

Intervention / Treatment
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* Diagnostic Test: mHBS
* Diagnostic Test: CT/MRI volumetry


Participation Criteria
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Eligibility Criteria
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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 will be excluded if younger than 18 years-old, pregnant, or if the hepatectomy is associated with another major non-liver procedure. Patients will also be excluded if they do not qualify for major hepatectomy following FLRF or FLRV assessment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Hypothesis: Using Future Liver Remnant Function (FLRF) through 99mTc-mebrofenin hepatobiliary scintigraphy (mHBS) to select patients for major hepatectomy will reduce the rate of Post-hepatectomy liver failure (PHLF), compared to our standard-of-care Future Liver Remnant Volume (FLRV) calculations for patient selection. Methods: This is a prospective pilot study designed to evaluate feasibility and safety in the Canadian settings and will include patients undergoing major liver resection at the Queen Elizabeth II Health Sciences Centre (QEII) in Halifax, Canada, and at McGill University Health Centre in Montreal, Canada (McGill). Recruited patients, irrespective of their underlying liver quality will be randomly assigned via block randomization to have either preoperative FLRV assessment by CT/MRI volumetry or preoperative FLRF risk assessment via mHBS.
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-hepatectomy liver failure (PHLF) | Post-hepatectomy liver failure (PHLF) | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Postoperative complications as per Clavien-Dindo classification | Postoperative complications as per Clavien-Dindo classification | 30 days | 
| Hospital length of stay | Hospital length of stay | 30 days | 
| 30-day mortality | 30-day mortality | 30 days |