AMRI vs. Ultrasound for Liver Cancer Surveillance

Overseen By Yesenia Covarrubias

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, San Diego

Disqualifiers: Liver cancer, Pregnancy, Nursing, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

150 Participants Needed

Trial Summary

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the drug Gadoxetate Disodium for liver cancer surveillance?

Research shows that using Gadoxetate Disodium in MRI scans helps detect liver cancer at an earlier stage compared to ultrasound alone, leading to better survival rates and slower disease progression in patients with liver cirrhosis. ^{1 2 3 4 5}

Is gadoxetate disodium safe for use in humans?

Gadoxetate disodium, used for liver MRI, is generally safe and well-tolerated in humans, with only 1.7% of 8194 patients experiencing related adverse events like shortness of breath and nausea. No deaths were reported in the studies. ^{6 7 8 9 10}

How is the treatment Gadoxetate Disodium different from other liver cancer surveillance methods?

Gadoxetate Disodium is used in an abbreviated MRI (AMRI) approach, which is a high-sensitivity alternative to ultrasound for liver cancer surveillance, especially in patients where ultrasound may not work well, like those with cirrhosis or obesity. This treatment involves a special contrast agent that enhances MRI images, making it easier to detect early-stage liver cancer. ^{2 11 12 13 14}

What is the purpose of this trial?

This study compares gadolinium contrast-enhanced Abbreviated MRI (AMRI) to standard ultrasound for Hepatocellular Carcinoma (HCC) screening and surveillance in subjects with liver cirrhosis.

Research Team

Claude B Sirlin, MD

Principal Investigator

University of California, San Diego

Eligibility Criteria

This trial is for adults of any gender and ethnicity with liver cirrhosis who can sign consent, complete research procedures, and allow access to their clinical data. It's not for those under 18, pregnant or nursing women, patients with a history of liver cancer or known allergies to gadolinium agents, or anyone contraindicated for MRI.

Inclusion Criteria

Subject has been fully informed and has personally signed and dated the written Informed Consent and Health Insurance Portability and Accountability Act (HIPAA) documents

Subject is able and willing to complete required research procedures (screening/enrollment, clinical evaluation, safety procedures, lab collection if needed, research AMRI exam, research US exam) and the three optional surveys (if subject opts in for that) within specified time windows, and is willing to allow the study team to review clinical data including but not limited to other clinical radiology reports and images.

Adults of any gender and ethnic background with liver cirrhosis, no matter what caused it.

Exclusion Criteria

VA patient

Does not meet UC San Diego Intravenous Contrast Media Guidelines for administration of Eovist*

History of any liver cancer

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo one ultrasound and one abbreviated MR exam for HCC detection

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

up to 12 months

Treatment Details

Interventions

• Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid

Trial Overview The study is testing if an Abbreviated MRI (AMRI) using Gadolinium contrast is better than standard ultrasound in screening for Hepatocellular Carcinoma (HCC) in people with liver cirrhosis. Participants will undergo both AMRI and ultrasound exams.

Participant Groups

Group I: Single arm Experimental Treatment 1 Intervention

This is a single arm study in which all participants have one ultrasound and one abbreviated MR exam

Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Primovist for:

• Hepatocellular carcinoma (HCC) diagnosis
• Liver lesion detection

Approved in United States as Eovist for:

• Hepatocellular carcinoma (HCC) diagnosis
• Liver lesion detection

Approved in Japan as Primovist for:

• Hepatocellular carcinoma (HCC) diagnosis
• Liver lesion detection

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma

Industry Sponsor

Trials

28

Recruited

126,000+

Icahn School of Medicine at Mount Sinai

Collaborator

Trials

933

Recruited

579,000+

Findings from Research

In a study of 95 cirrhotic patients with hepatocellular carcinoma, gadoxetic acid (Gd-EOB-DTPA) showed lower contrast-to-noise ratios (CNR) during the arterial phase compared to gadobenate dimeglumine, although this difference was not statistically significant.

Gd-EOB-DTPA demonstrated higher CNR during the portal venous and equilibrium phases, suggesting it may provide better imaging quality in these later phases, but overall differences in enhancement were not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Dynamic Phase Enhancement of Hepatocellular Carcinoma Using Gadoxetate Disodium vs Gadobenate Dimeglumine. Tirkes, T., Mehta, P., Aisen, AM., et al.[2022]

In a study of 382 high-risk patients for hepatocellular carcinoma (HCC), gadoxetic acid-enhanced MRI (AMRI) methods demonstrated significantly higher sensitivity for detecting early-stage HCC compared to ultrasound-only surveillance, with sensitivities of 90.7% for combined MRI and 86.0% for AMRI-only versus only 27.9% for ultrasound.

The sequential approach of complete gadoxetic acid-enhanced MRI followed by AMRI showed the highest accuracy at 96.9%, outperforming both AMRI-only and ultrasound-only methods, indicating that MRI-based surveillance is more effective for early detection of HCC in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abbreviated magnetic resonance imaging vs ultrasound for surveillance of hepatocellular carcinoma in high-risk patients. Park, HJ., Kim, SY., Singal, AG., et al.[2022]

In a study of 421 patients with cirrhosis, those who underwent surveillance with Gd-EOB-DTPA-enhanced MRI in addition to ultrasonography (USG) had a significantly higher rate of early-stage hepatocellular carcinoma (HCC) detection (95.2%) compared to those who only had USG (83.7%).

Patients in the Gd-EOB-DTPA-enhanced MRI group also experienced significantly better clinical outcomes, including longer overall survival and time to progression, indicating that this imaging technique can enhance HCC surveillance in cirrhosis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adding MRI as a Surveillance Test for Hepatocellular Carcinoma in Patients with Liver Cirrhosis Can Improve Prognosis. Yu, SJ., Yoo, JJ., Lee, DH., et al.[2023]

Gadoxetate acid (Gd-EOB-DTPA) is a safe and effective liver-specific contrast agent that enhances MRI imaging, improving the detection and characterization of hepatocellular carcinoma (HCC) compared to unenhanced MRI and other imaging methods.

The use of gadoxetate acid allows for better differentiation of early HCC from benign or premalignant nodules, which is crucial for determining appropriate management strategies and improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gadoxetate Acid-Enhanced MR Imaging for HCC: A Review for Clinicians. Chanyaputhipong, J., Low, SC., Chow, PK.[2021]

Gd-EOB-DTPA-enhanced MRI significantly outperformed multidetector-row computed tomography (MDCT) in detecting hepatocellular carcinoma (HCC), identifying 76.1% of nodules compared to 35.8% with MDCT, which led to changes in treatment decisions for 11 out of 25 patients.

The use of Gd-EOB-DTPA-enhanced MRI was associated with a lower recurrence rate of 4% after living donor liver transplant (LDLT), compared to a 13.9% mortality rate in patients who did not receive this imaging, suggesting its potential to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Impact of Gadoxetic Acid-Enhanced Magnetic Resonance Imaging on Living Donor Liver Transplant. Chen, YS., Lim, WX., Lin, AN., et al.[2022]

Gadoxetic acid disodium (Gd-EOB-DTPA) was found to be well tolerated, indicating a good safety profile for patients undergoing MRI for liver lesions.

The use of Gd-EOB-DTPA-enhanced MRI significantly improved the accurate characterization of liver lesions compared to unenhanced MRI and spiral CT, with correct characterization rates of 96% for combined MRI versus 84% and 85% for the other methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved characterization of focal liver lesions with liver-specific gadoxetic acid disodium-enhanced magnetic resonance imaging: a multicenter phase 3 clinical trial. Raman, SS., Leary, C., Bluemke, DA., et al.[2021]

In a study involving 33 patients, Gd-EOB-DTPA significantly improved the detection of focal liver lesions, with effective results observed at doses as low as 12.5 mumol per kilogram.

The use of Gd-EOB-DTPA was found to be safe, with no significant adverse effects or changes in vital signs, making it a reliable contrast agent for liver imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II clinical evaluation of Gd-EOB-DTPA: dose, safety aspects, and pulse sequence. Reimer, P., Rummeny, EJ., Shamsi, K., et al.[2022]

In a study involving 8194 patients across multiple countries, gadoxetate disodium was found to have a low adverse event rate of 1.7%, indicating it is generally safe for routine use in liver MRI.

The most common adverse events were mild, such as dyspnea and nausea, and importantly, no serious adverse events were related to the drug in the pediatric population, highlighting its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of gadoxetate disodium: results from six clinical phase IV studies in 8194 patients. Endrikat, J., Kim, SY., Sakaguchi, T., et al.[2018]

Gadoxetic acid (Gd-EOB-DTPA) is a liver-specific contrast agent for MRI that has shown high safety margins, with no observed adverse effects at clinical doses in humans, even after repeated administration.

Animal studies indicated that lethal doses were significantly higher than clinical doses, and there were no signs of reproductive, developmental, or genotoxic toxicity, confirming its well-tolerated profile for diagnostic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical safety evaluation of Gd-EOB-DTPA (Primovist). Döhr, O., Hofmeister, R., Treher, M., et al.[2019]

In a study involving 234 Chinese patients, the liver-specific contrast agent gadoxetate disodium (Gd-EOB-DTPA) significantly improved the sensitivity of detecting liver lesions by 9.46% compared to pre-contrast imaging, especially for lesions smaller than 1 cm.

Gd-EOB-DTPA not only enhanced lesion detection but also improved the diagnostic accuracy in classifying these lesions, demonstrating its efficacy and safety for use in patients with liver lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gd-EOB-DTPA-enhanced magnetic resonance imaging for focal liver lesions in Chinese patients: a multicenter, open-label, phase III study. Zeng, MS., Ye, HY., Guo, L., et al.[2022]

Abbreviated MRI (AMRI) protocols can effectively monitor hepatocellular carcinoma (HCC) with fewer sequences than traditional MRI, maintaining acceptable diagnostic performance.

Different AMRI options, such as non-contrast, dynamic, or hepatobiliary phase after gadoxetate injection, are available, but further research in a large multicenter study is needed to determine the optimal protocol for HCC surveillance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abbreviated MRI for HCC surveillance: is it ready for clinical use? Vietti Violi, N., Taouli, B.[2021]

Abbreviated magnetic resonance imaging (AMRI) is emerging as a high-sensitivity alternative to ultrasound for monitoring patients with chronic liver disease for early-stage hepatocellular carcinoma (HCC), especially in those with cirrhosis or obesity where ultrasound may not be effective.

Three AMRI techniques—non-contrast, dynamic contrast-enhanced, and hepatobiliary phase contrast-enhanced—have been developed, each tailored for HCC detection, and the review suggests cautiously recommending AMRI when ultrasound is inadequate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternative approach of hepatocellular carcinoma surveillance: abbreviated MRI. Brunsing, RL., Fowler, KJ., Yokoo, T., et al.[2021]

Non-contrast abbreviated MRI (NC-AMRI) has limited sensitivity for detecting hepatocellular carcinoma (HCC) at 61.5%, while dynamic AMRI (Dyn-AMRI) and hepatobiliary phase AMRI (HBP-AMRI) show significantly higher sensitivities of 84.6% and 80.8%, respectively.

All abbreviated MRI methods demonstrated high specificity and were found to be cost-effective compared to ultrasound for HCC screening, providing a life-year gain of 3-12 months at incremental costs of less than $12,000.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gadoxetate-enhanced abbreviated MRI is highly accurate for hepatocellular carcinoma screening. Vietti Violi, N., Lewis, S., Liao, J., et al.[2021]

Abbreviated magnetic resonance imaging (AMRI) has emerged as a promising technique for liver imaging, with various protocols like noncontrast AMRI, hepatobiliary-AMRI, and dynamic-AMRI being utilized for different liver conditions.

AMRI is effective for screening and monitoring liver diseases, including hepatocellular carcinoma, nonalcoholic fatty liver disease, and liver metastases in colorectal cancer patients, highlighting its versatility in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abbreviated Liver Magnetic Resonance Imaging Protocols and Applications. Altinmakas, E., Taouli, B.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Comparison of Dynamic Phase Enhancement of Hepatocellular Carcinoma Using Gadoxetate Disodium vs Gadobenate Dimeglumine. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Abbreviated magnetic resonance imaging vs ultrasound for surveillance of hepatocellular carcinoma in high-risk patients. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Adding MRI as a Surveillance Test for Hepatocellular Carcinoma in Patients with Liver Cirrhosis Can Improve Prognosis. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Gadoxetate Acid-Enhanced MR Imaging for HCC: A Review for Clinicians. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Clinical Impact of Gadoxetic Acid-Enhanced Magnetic Resonance Imaging on Living Donor Liver Transplant. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Improved characterization of focal liver lesions with liver-specific gadoxetic acid disodium-enhanced magnetic resonance imaging: a multicenter phase 3 clinical trial. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Phase II clinical evaluation of Gd-EOB-DTPA: dose, safety aspects, and pulse sequence. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Safety of gadoxetate disodium: results from six clinical phase IV studies in 8194 patients. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Preclinical safety evaluation of Gd-EOB-DTPA (Primovist). [2019]

10. Singapore pubmed.ncbi.nlm.nih.gov

Gd-EOB-DTPA-enhanced magnetic resonance imaging for focal liver lesions in Chinese patients: a multicenter, open-label, phase III study. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Abbreviated MRI for HCC surveillance: is it ready for clinical use? [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Alternative approach of hepatocellular carcinoma surveillance: abbreviated MRI. [2021]

13. Germany pubmed.ncbi.nlm.nih.gov

Gadoxetate-enhanced abbreviated MRI is highly accurate for hepatocellular carcinoma screening. [2021]

14. United States pubmed.ncbi.nlm.nih.gov

Abbreviated Liver Magnetic Resonance Imaging Protocols and Applications. [2022]