Preventing Liver Cancer Mortality Through Imaging With Ultrasound vs. MRI (PREMIUM)

April 15, 2026 updated by: VA Office of Research and Development

CSP #2023 - Preventing Liver Cancer Mortality Through Imaging With Ultrasound vs. MRI (The PREMIUM Study)

The study is a randomized trial of two different screening methods for early detection of liver cancer in patients with cirrhosis of the liver. The goal of PREMIUM is to compare an abbreviated version of the diagnostic gold standard for HCC (aMRI) +AFP to the standard-of-care screening (US+AFP) in patients at high risk of developing HCC. The investigators hypothesize that HCC will be detected at earlier stages, allowing for more curative treatments and resulting in a reduction in HCC-related mortality.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Study Design. The investigators propose to conduct a randomized controlled trial of screening for hepatocellular carcinoma (HCC) by ultrasound (US)+serum alpha fetoprotein (AFP) every 6 months (the current standard-of-care) versus abbreviated MRI (aMRI)+AFP every 6 months among patients with cirrhosis who have a high risk of HCC (estimated annual HCC risk >2.5%).

Study Population. Patients ages 18-75 with cirrhosis (standard histologic, radiologic, or clinical criteria) of any etiology, with estimated annual HCC risk >2.5%. Exclusion Criteria: Prior HCC; Child C Cirrhosis (CTP score 10); MELD score >20; Listed for liver transplantation; Contra-indications to MRI; Comorbidities with limited life expectancy defined by a cirrhosis-specific comorbidity index (CirCom) score 3.

Study Setting. 47 VA Medical Centers will recruit on average 100 patients/site over 3 years. These recruitment sites, which have already been identified, have adequate numbers of cirrhosis patients eligible for screening, a qualified hepatologist and radiologist to serve as local site investigators (LSIs), adequate MRI and US capacity, and access to a multidisciplinary liver tumor board (MLTB).

Target Sample Size. N=2350 per group, total N=4700.

Randomization. The randomization scheme will be random permuted with variable block size and will be stratified by medical center and MELD score.

Intervention. Participants will be randomized in a 1:1 ratio to one of two screening arms:

a. Abdominal aMRI+ serum AFP every 6 months, OR b. Abdominal US+ serum AFP every 6 months, from the time of recruitment until the end of study Year 8.

The aMRI protocol will include only T1-weighted pre-contrast and dynamic contrast-enhanced images utilizing an extracellular gadolinium-based contrast agent. aMRI takes only ~15 minutes to perform. Enrollment will occur in Years 1-3, screening per protocol will continue through Year 8, and follow-up for mortality will continue through Year 8. Analysis and publication will be in Year 9.

Primary Outcome. HCC-related mortality.

Power Calculations. The study is powered to detect a minimum relative reduction in HCC-related mortality of 35% in the aMRI+AFP arm compared to the US+AFP arm, i.e. a reduction in cumulative HCC-related mortality at Year 8 from 7.1 per 100 patients in the US+AFP arm to 4.6 per 100 patients in the aMRI+AFP arm (absolute difference in HCC-related mortality of 2.5 per 100 patients), adjusted for dropout due to death from other causes or withdrawals, with power 88% and two-sided alpha 0.05.

Study Type

Interventional

Enrollment (Estimated)

4700

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233-1927
        • Recruiting
        • Birmingham VA Medical Center, Birmingham, AL
        • Contact:
    • Arizona
      • Tucson, Arizona, United States, 85723-0001
        • Recruiting
        • Southern Arizona VA Health Care System, Tucson, AZ
        • Contact:
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Recruiting
        • Central Arkansas Veterans Healthcare System , Little Rock, AR
        • Contact:
    • California
      • Long Beach, California, United States, 90822
        • Recruiting
        • VA Long Beach Healthcare System, Long Beach, CA
        • Contact:
      • Palo Alto, California, United States, 94304-1207
        • Recruiting
        • VA Palo Alto Health Care System, Palo Alto, CA
        • Contact:
      • Sacramento, California, United States, 95655-4200
        • Recruiting
        • VA Northern California Health Care System, Mather, CA
        • Contact:
      • San Diego, California, United States, 92161-0002
        • Recruiting
        • VA San Diego Healthcare System, San Diego, CA
        • Contact:
          • Heather Patton, MD
          • Phone Number: 858-260-0190
      • West Los Angeles, California, United States, 90073-1003
        • Recruiting
        • VA Greater Los Angeles Healthcare System, West Los Angeles, CA
        • Contact:
    • Colorado
      • Aurora, Colorado, United States, 80045-7211
        • Recruiting
        • Rocky Mountain Regional VA Medical Center, Aurora, CO
        • Contact:
    • Connecticut
      • West Haven, Connecticut, United States, 06516-2770
        • Recruiting
        • VA Connecticut Healthcare System West Haven Campus, West Haven, CT
        • Contact:
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20422-0001
        • Recruiting
        • Washington DC VA Medical Center, Washington, DC
        • Contact:
    • Florida
      • Miami, Florida, United States, 33125
        • Recruiting
        • Miami VA Healthcare System, Miami, FL
        • Contact:
      • Tampa, Florida, United States, 33612
        • Active, not recruiting
        • James A. Haley Veterans' Hospital, Tampa, FL
    • Georgia
      • Decatur, Georgia, United States, 30033-4004
        • Recruiting
        • Atlanta VA Medical and Rehab Center, Decatur, GA
        • Contact:
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02130-4817
        • Recruiting
        • VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
        • Contact:
    • Michigan
      • Ann Arbor, Michigan, United States, 48105-2303
        • Recruiting
        • VA Ann Arbor Healthcare System, Ann Arbor, MI
        • Contact:
    • Missouri
      • St Louis, Missouri, United States, 63106-1621
        • Recruiting
        • St. Louis VA Medical Center John Cochran Division, St. Louis, MO
        • Contact:
          • Melissa Kaltenbach, MD
          • Phone Number: 57030 314-652-4100
    • Nebraska
      • Omaha, Nebraska, United States, 68105-1850
        • Recruiting
        • Omaha VA Nebraska-Western Iowa Health Care System, Omaha, NE
        • Contact:
    • New York
      • New York, New York, United States, 10010-5011
        • Recruiting
        • VA NY Harbor Healthcare System, New York, NY
        • Contact:
      • The Bronx, New York, United States, 10468-3904
        • Recruiting
        • James J. Peters VA Medical Center, Bronx, NY
        • Contact:
    • North Carolina
      • Durham, North Carolina, United States, 27705-3875
        • Recruiting
        • Durham VA Medical Center, Durham, NC
        • Contact:
    • Ohio
      • Cleveland, Ohio, United States, 44106-1702
        • Recruiting
        • Louis Stokes VA Medical Center, Cleveland, OH
        • Contact:
    • Oregon
      • Portland, Oregon, United States, 97207-2964
        • Recruiting
        • VA Portland Health Care System, Portland, OR
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104-4551
        • Recruiting
        • Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
        • Contact:
    • South Carolina
      • Charleston, South Carolina, United States, 29401-5703
        • Recruiting
        • Ralph H. Johnson VA Medical Center, Charleston, SC
        • Contact:
      • Columbia, South Carolina, United States, 29209-1638
        • Recruiting
        • Wm. Jennings Bryan Dorn VA Medical Center, Columbia, SC
        • Contact:
    • Texas
      • Dallas, Texas, United States, 75216-7167
        • Recruiting
        • VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
        • Contact:
      • Houston, Texas, United States, 77030-4211
        • Recruiting
        • Michael E. DeBakey VA Medical Center, Houston, TX
        • Contact:
    • Utah
      • Salt Lake City, Utah, United States, 84148-0001
        • Recruiting
        • VA Salt Lake City Health Care System, Salt Lake City, UT
        • Contact:
    • Washington
      • Seattle, Washington, United States, 98108-1532
        • Recruiting
        • VA Puget Sound Health Care System Seattle Division, Seattle, WA
        • Contact:
        • Study Chair:
          • George N. Ioannou, MD MS
    • Wisconsin
      • Madison, Wisconsin, United States, 53705-2254
        • Recruiting
        • William S. Middleton Memorial Veterans Hospital, Madison, WI
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Cirrhosis due to any underlying etiology diagnosed by one or more of the following:

    • Histology of liver biopsy
    • Radiologic criteria (nodular liver, evidence of portal hypertension)
    • Clinical signs of cirrhosis (gastroesophageal varices, ascites, hepatic encephalopathy)
    • Vibration controlled transient elastography (VCTE, specifically Fibroscan, which is available in all participating sites) with liver stiffness >12.5kPa or magnetic resonance elastography >5.0 kPa

  2. High Risk of Liver Cancer: This will be defined by one or more of the following:

    • Current HCV infection (detectable HCV RNA)
    • FIB-4 score 3.25, within 6 months of randomization
    • Estimated annual HCC incidence >2.5%, within 6 months of randomization, calculated by VA-specific models that the investigators developed (available on the national VA ALD Dashboard and at www.hccrisk.com).
  3. Age 18-75
  4. Able to provide informed consent

Exclusion Criteria:

  1. Prior diagnosis or of HCC
  2. Current suspicion of HCC
  3. Prior receipt of organ transplantation
  4. Currently listed for organ transplantation.
  5. Participation in a conflicting HCC screening trial
  6. Advanced liver dysfunction, defined by Child C Cirrhosis (CTP score 10), or MELD score >20, within 6 months prior to randomization
  7. Glomerular Filtration Rate (GFR) <30 ml/min
  8. Multiple comorbid conditions resulting in limited life expectancy, defined by a cirrhosis-specific comorbidity index (CirCom)112 score 3. Of note, early stage malignancies of the bladder, lung, or prostate will not be excluded.
  9. Estimated life expectancy <5 years as determined by the clinical judgement of the Study Investigator

  10. Contraindications to undergoing contrast-enhanced MRI:

    • Allergy to gadolinium-based contrast agents
    • MRI-incompatible implantable devices (e.g. pacemakers, defibrillators, resynchronization devices)
    • Implantable neurostimulation device
    • Implantable cochlear implant/ear implant
    • Drug infusion pumps (e.g. insulin pump, analgesic or chemotherapy pumps)
    • Metallic foreign bodies in or around the eye
    • Metallic fragments, such as bullets, shotgun pellets or shrapnel
    • Metallic body piercings that cannot be removed
    • Cerebral artery aneurysm clips
    • Severe claustrophobia
    • Unable to fit on MRI machine due to weight (weight >400lbs) or body habitus
  11. Inability to complete planned study visits (e.g. lives too far from VA, no transportation, etc.)
  12. Currently pregnant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Abdominal Ultrasound Screening with serum AFP
abdominal ultrasound (US)+serum alpha fetoprotein (AFP) every 6 months from the time of recruitment until the end of year 8
Other: Abdominal Ultrasound Screening with serum AFP
abdominal ultrasound (US)+serum alpha fetoprotein (AFP) every 6 months from the time of recruitment until the end of year 8
Other: Abbreviated Magnetic Resonance Imaging with serum AFP
Abdominal aMRI+ serum AFP every 6 months from the time of recruitment until the end of year 8
Other: Abbreviated Magnetic Resonance Imaging with serum AFP
Abdominal aMRI+ serum AFP every 6 months from the time of recruitment until the end of year 8

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hepatocellular Carcinoma Mortality
Time Frame: 8 years
death due to liver cancer
8 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Stage of Hepatocellular Carcinoma at diagnosis
Time Frame: 8 years
Stage of Hepatocellular Carcinoma at time of diagnosis
8 years
Receipt of potentially curative treatments for Hepatocellular Carcinoma
Time Frame: 8 years
Receipt of potentially curative treatments for Hepatocellular Carcinoma
8 years
Overall Survival
Time Frame: 8 years
overall survival of liver cancer
8 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

VA Office of Research and Development

Investigators

  • Study Chair: George N. Ioannou, MD MS, VA Puget Sound Health Care System Seattle Division, Seattle, WA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 3, 2023

Primary Completion (Estimated)

September 1, 2030

Study Completion (Estimated)

September 1, 2031

Study Registration Dates

First Submitted

August 1, 2022

First Submitted That Met QC Criteria

August 1, 2022

First Posted (Actual)

August 3, 2022

Study Record Updates

Last Update Posted (Actual)

April 21, 2026

Last Update Submitted That Met QC Criteria

April 15, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023 (GRAMMY Museum Foundation)

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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