Comparison of Contrast Agents in Liver Magnetic Resonance (MR) for the Detection of Hepatic Metastases

Evaluation of Liver Magnetic Resonance (MR) With an Abbreviated Gadobenate Dimeglumine Hepatobiliary Phase Protocol in Comparison to Liver MR With Gadoxetate Disodium for the Detection of Hepatic Metastases

If an abbreviated hepatobiliary phase (HBP) protocol liver MR with gadobenate dimeglumine is shown clinically comparable to standard of care liver MR with gadoxetate disodium for detecting hepatic metastasis from colorectal cancer, its use will save time, cost, and patients' effort.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer; Liver Metastases; Oligometastatic Disease
• Intervention / Treatment: Drug: Gadoxetate disodium; Drug: Gadobenate dimeglumine

Detailed Description

The goal is to:

• Estimate and compare the diagnostic performance, including sensitivity, specificity, positive/negative predictive value, and area under the receiver operating characteristics (AUROC), of abbreviated protocol liver magnetic resonance (MR) with hepatobiliary phase (HBP) using gadobenate dimeglumine for detecting liver metastases, with 1) abbreviated protocol liver MR with HBP using gadoxetate disodium, 2) standard of care complete protocol liver MR using gadoxetate disodium, and 3) complete protocol liver MR using gadobenate dimeglumine.
• Estimate and compare quantitative measures of HBP images (liver enhancement ratio, lesion contrast to noise and signal to noise ratios [CNR and SNR]) for both gadobenate dimeglumine and gadoxetate disodium.
• Qualitatively assess the preference, or lack thereof, of radiologists regarding the images generated by abbreviated protocol liver MR with HBP using gadobenate dimeglumine versus abbreviated protocol liver MR with HBP using gadoxetate disodium.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado 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:

• Colorectal cancer patients
• Age 18-80 years
• No prior treatment including surgery
• Prior imaging with suspected liver metastasis

Exclusion Criteria:

• Age < 18 years or > 80 years
• eGFR < 30 ml/min/1.73 m2
• Previous reaction to gadolinium contrast agents
• History of claustrophobia or movement disorders likely to impact image quality
• Non-MR safe implants or metallic foreign bodies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Gadoxetate disodium exam first, Gadobenate Dimeglumine exam second; The subjects will be randomized into two groups. Both groups will undergo two complete protocol liver magnetic resonance imaging (MRI) for known or suspected colorectal cancer (CRC) metastasis, one exam with gadoxetate disodium and the other exam with gadobenate dimeglumine, within an interval of 3-20 days, but in opposite order, determined randomly.	Drug: Gadoxetate disodium; Gadoxetate disodium MR contrast is now mainly used for the purpose of HBP liver MR imaging to save MR scanner time and total examination time.; Other Names: Primovist; Eovist; Drug: Gadobenate dimeglumine; The most commonly used MR contrast agent in abdominal imaging is gadobenate dimeglumine, which has mainly the characteristics of an extracellular agent used for most indications of MR examinations.; Other Names: MultiHance
Experimental: Gadobenate Dimeglumine exam first, Gadoxetate disodium exam second; The subjects will be randomized into two groups. Both groups will undergo two complete protocol liver MRI for known or suspected CRC metastasis, one exam with gadoxetate disodium and the other exam with gadobenate dimeglumine, within an interval of 3-20 days, but in opposite order, determined randomly.	Drug: Gadoxetate disodium; Gadoxetate disodium MR contrast is now mainly used for the purpose of HBP liver MR imaging to save MR scanner time and total examination time.; Other Names: Primovist; Eovist; Drug: Gadobenate dimeglumine; The most commonly used MR contrast agent in abdominal imaging is gadobenate dimeglumine, which has mainly the characteristics of an extracellular agent used for most indications of MR examinations.; Other Names: MultiHance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preference of Radiologists for the Hepatobiliary Phase Images Generated by MultiHance (amHBP) Versus Eovist (aeHBP).	The quality of amHBP and aeHBP images was assessed using ordinal response mixed effect models that included right/left image position as a covariate. For each paired comparison, radiologists indicated their preferred hepatobiliary phase image.	1 month
Quantitative Timing Measures for Hepatobiliary Phase MRI	Measures of timing used to obtain hepatobiliary phase images.	1 month
Estimate and Compare Quantitative Measures of HBP Images (Liver Enhancement Ratio, Lesion Contrast to Noise and Signal to Noise Ratios [CNR and SNR]) for Both Gadobenate Dimeglumine and Gadoxetate Disodium.	A single reader analyzed paired Eovist and MultiHance hepatobiliary phase images (N=10 paired datasets). Quantitative metrics included liver-to-metastasis, liver-to-spleen, liver-to-muscle, and liver-to-blood contrast ratios (CNR's), as well as liver signal-to-noise ratio (SNR). All CNR's were calculated as signal intensity of liver relative to the reference tissue, with liver SNR liver signal/liver noise. Higher contrast ratios and higher SNR values indicate greater liver enhancement and improved lesion conspicuity.	1 month
Estimate and Compare Qualitative Measures of HBP Images for Both Gadobenate Dimeglumine and Gadoxetate Disodium.	A single reader performed a qualitative assessment of Dynamic and Hepatobiliary Phase Image Quality (Likert scale 1-5) for both Eovist and MultiHance Hepatobiliary Phase images (N=10 paired data). Higher scores indicate better image quality.	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic Performance of Gadobenate Dimeglumine	The primary performance diagnostic will be sensitivity, similar to the recently published retrospective study by Canellas et al. (2019). In addition to other diagnostic performance metrics of interest (e.g., specificity, AUROC), lesions will be analyzed descriptively in terms of number of metastases detected and lesion size.	1 year
Compare Sensitivity and Specificity,	The primary analysis will use pathology as the gold standard, if available, but will revert to long term imaging in the absence of pathology. To address the potential impact of this limitation, we will also conduct an exploratory analysis to compare the sensitivity and specificity of the imaging methods by each gold standard.	17 months
Test Validity of Imaging Methods	We will also conduct an exploratory analysis to test the validity of long term imaging as a gold standard against available pathology reports.	17 months
Compare Patient Time Associated With Imaging Method	In addition to analyses for the primary aims, additional analyses will be conducted to examine patient time associated with each imaging method; time metrics can be compared between imaging methods in absolute terms, but also proportionally to sensitivity.	17 months
Compare Cost Associated With Imaging Method	In addition to analyses for the primary aims, additional analyses will be conducted to examine cost associated with each imaging method; cost metrics can be compared between imaging methods in absolute terms, but also proportionally to sensitivity.	17 months

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Cancer Institute (NCI); Bracco Diagnostics, Inc
• Investigators: Principal Investigator: Nikhil Madhuripan, MD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2021
• Primary Completion (Actual): May 6, 2025
• Study Completion (Actual): May 8, 2025

Study Registration Dates

• First Submitted: July 1, 2021
• First Submitted That Met QC Criteria: July 13, 2021
• First Posted (Actual): July 22, 2021

Study Record Updates

• Last Update Posted (Actual): September 25, 2026
• Last Update Submitted That Met QC Criteria: August 31, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; gadobenic acid; gadolinium ethoxybenzyl DTPA
• Other Study ID Numbers: 19-1045.cc; P30CA046934 (U.S. NIH Grant/Contract)

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