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Carcinoma, HepatocellularPREMIUMNCT05486572

Preventing Liver Cancer Mortality Through Imaging With Ultrasound vs. MRI

A study testing Abbreviated Magnetic Resonance Imaging with serum AFP and Abdominal Ultrasound Screening with serum AFP in people with Carcinoma, Hepatocellular and Cirrhosis, run by VA Office of Research and Development at 34 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Carcinoma, Hepatocellular, Cirrhosis
What is being tested?
Abbreviated Magnetic Resonance Imaging with serum AFP and Abdominal Ultrasound Screening with serum AFP
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4,700 participants
Where
34 sitesUnited States
Study dates
3 Nov 2023to 1 Sep 2031
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • High Risk of Liver Cancer: This will be defined by one or more of the following:
Show all 11Show fewer
  • 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).
  • Age 18-75
  • Able to provide informed consent

Who cannot join

  • Prior diagnosis or of HCC
  • Current suspicion of HCC
  • Prior receipt of organ transplantation
  • Currently listed for organ transplantation.
  • Participation in a conflicting HCC screening trial
  • Advanced liver dysfunction, defined by Child C Cirrhosis (CTP score 10), or MELD score >20, within 6 months prior to randomization
Show all 23Show fewer
  • Glomerular Filtration Rate (GFR) <30 ml/min
  • 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.
  • Estimated life expectancy <5 years as determined by the clinical judgement of the Study Investigator
  • 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
  • Inability to complete planned study visits (e.g. lives too far from VA, no transportation, etc.)
  • Currently pregnant

Trial locations and contacts

34 sites in 1 country. Contact the study team or a site near you to ask about taking part.

George N Ioannou, MD MS contact

(206) 277-3136

George.Ioannou@va.gov

34 sites in 1 country

United States34 sites, 33 recruiting

  • VA Ann Arbor Healthcare System, Ann Arbor, MI

    Ann Arbor, Michigan, 48105-2303

    Grace L Su, MD, grace.su@va.gov

    Recruiting

  • Rocky Mountain Regional VA Medical Center, Aurora, CO

    Aurora, Colorado, 80045-7211

    Ashley M Lane, MD, 720-723-6773, ashley.lane6@va.gov

    Recruiting

  • Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD

    Baltimore, Maryland, 21201

    Zurabi Lominadze, MD, 502-541-7093, Zurabi.Lominadze@va.gov

    Recruiting

  • Birmingham VA Medical Center, Birmingham, AL

    Birmingham, Alabama, 35233-1927

    James Callaway, MD, 205-933-8101, James.Callaway@va.gov

    Recruiting

  • VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

    Boston, Massachusetts, 02130-4817

    Gyorgy Baffy, MD, gyorgy.baffy@va.gov

    Recruiting

  • Ralph H. Johnson VA Medical Center, Charleston, SC

    Charleston, South Carolina, 29401-5703

    Don Rockey, MD, 843-577-5011, Don.Rockey@va.gov

    Recruiting

  • Louis Stokes VA Medical Center, Cleveland, OH

    Cleveland, Ohio, 44106-1702

    Percia Davitkav, MD, percia.davitkov@va.gov

    Recruiting

  • Wm. Jennings Bryan Dorn VA Medical Center, Columbia, SC

    Columbia, South Carolina, 29209-1638

    Nicholas Hoppmann, MD, Nicholas.Hoppmann2@va.gov

    Recruiting

  • VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX

    Dallas, Texas, 75216-7167

    Jacqueline Oleary, MD, 214-857-0403, Jacqueline.Oleary@va.gov

    Recruiting

  • Atlanta VA Medical and Rehab Center, Decatur, GA

    Decatur, Georgia, 30033-4004

    Thuy-Van Hang, MD, 404-321-6111 ext. x2067, Thuy-Van.Hang@va.gov

    Recruiting

  • Durham VA Medical Center, Durham, NC

    Durham, North Carolina, 27705-3875

    Cynthia Moylan, MD, 919-286-0411, Cynthia.Moylan@va.gov

    Recruiting

  • Michael E. DeBakey VA Medical Center, Houston, TX

    Houston, Texas, 77030-4211

    Ruben Hernaez, MD, ruben.hernaez@va.gov

    Recruiting

  • Central Arkansas Veterans Healthcare System , Little Rock, AR

    Little Rock, Arkansas, 72205

    Ragesh Thandassery, MD, Ragesh.Thandassery@va.gov

    Recruiting

  • VA Long Beach Healthcare System, Long Beach, CA

    Long Beach, California, 90822

    Morgan R Timothy, MD, morgan.timothy@va.gov

    Recruiting

  • Robley Rex VA Medical Center, Louisville, KY

    Louisville, Kentucky, 40206-1433

    Ashutosh Barve, MD, 502-287-4000, ashutosh.barve@va.gov

    Recruiting

  • William S. Middleton Memorial Veterans Hospital, Madison, WI

    Madison, Wisconsin, 53705-2254

    Adnan Said, MD, adam.said@va.gov

    Recruiting

  • Miami VA Healthcare System, Miami, FL

    Miami, Florida, 33125

    Binu John, MD, 305-575-7000 ext. 176, Binu.John@va.gov

    Recruiting

  • VA NY Harbor Healthcare System, New York, NY

    New York, New York, 10010-5011

    Daniel Dileo, MD, 718-836-6600 ext. 6939, Daniel.Dileo@va.gov

    Recruiting

  • Omaha VA Nebraska-Western Iowa Health Care System, Omaha, NE

    Omaha, Nebraska, 68105-1850

    Peter Mannon, MD, peter.mannon@va.gov

    Recruiting

  • VA Palo Alto Health Care System, Palo Alto, CA

    Palo Alto, California, 94304-1207

    Cheung Ramsey, MD, 650-493-5000, ramsey.cheung@va.gov

    Recruiting

  • Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

    Philadelphia, Pennsylvania, 19104-4551

    David Kaplan, MD, david.kaplan@va.gov

    Recruiting

  • VA Portland Health Care System, Portland, OR

    Portland, Oregon, 97207-2964

    Janice Jou, MD, 503-220-8262 ext. 58126, Janice.Jou@va.gov

    Recruiting

  • VA Northern California Health Care System, Mather, CA

    Sacramento, California, 95655-4200

    Anthony Albanese, MD, anthony.albanese@va.gov

    Recruiting

  • Salisbury W.G. (Bill) Hefner VA Medical Center, Salisbury, NC

    Salisbury, North Carolina, 28144

    Leon Kundrotas, MD, 704-638-9000 ext. 32580, leon.kundrotas@va.gov

    Recruiting

  • VA Salt Lake City Health Care System, Salt Lake City, UT

    Salt Lake City, Utah, 84148-0001

    Tuan Pham, MD, 801-582-1565 ext. 1234, Tuan.Pham@va.gov

    Recruiting

  • VA San Diego Healthcare System, San Diego, CA

    San Diego, California, 92161-0002

    Heather Patton, MD, 858-260-0190

    Recruiting

  • VA Puget Sound Health Care System Seattle Division, Seattle, WA

    Seattle, Washington, 98108-1532

    George N Ioannou, MD MS, 206-277-3136, George.Ioannou@va.gov

    George N. Ioannou, MD MS

    Recruiting

  • St. Louis VA Medical Center John Cochran Division, St. Louis, MO

    St Louis, Missouri, 63106-1621

    Melissa Kaltenbach, MD, 314-652-4100 ext. 57030

    Recruiting

  • James A. Haley Veterans' Hospital, Tampa, FL

    Tampa, Florida, 33612

    Active, not recruiting

  • James J. Peters VA Medical Center, Bronx, NY

    The Bronx, New York, 10468-3904

    Tae H Lee, MD, 718-584-9000 ext. 3600, tae.lee@va.gov

    Recruiting

  • Southern Arizona VA Health Care System, Tucson, AZ

    Tucson, Arizona, 85723-0001

    Bhupesh Pokhrel, MD, 520-792-1450 ext. 1-4649, Bhupesh.Pokhrel@va.gov

    Recruiting

  • Washington DC VA Medical Center, Washington, DC

    Washington D.C., District of Columbia, 20422-0001

    Atoosa Rabiee, MD, 202-745-8000, Atoosa.Rabiee@va.gov

    Recruiting

  • VA Connecticut Healthcare System West Haven Campus, West Haven, CT

    West Haven, Connecticut, 06516-2770

    Sofia Jakab, MD, sofia.jakab@va.gov

    Recruiting

  • VA Greater Los Angeles Healthcare System, West Los Angeles, CA

    West Los Angeles, California, 90073-1003

    Joseph Pisegna, MD, joseph.pisegna@va.gov

    Recruiting

Other trials in United States

About this study

Official title: 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.

Read the 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:

  1. 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.

Being tested
Abbreviated Magnetic Resonance Imaging with serum AFP, Abdominal Ultrasound Screening with serum AFP
Keywords
hepatic, oncology, liver, chronic diseases; health services and systems, prospective, randomized, clinical trial, magnetic resonance imaging; ultrasonography, cirrhosis; liver cancer
Medical subject headings
Carcinoma, Hepatocellular, Fibrosis, Neoplasms, Chronic Disease, Liver Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Abbreviated Magnetic Resonance Imaging with serum AFPOther

    Abdominal aMRI+ serum AFP every 6 months from the time of recruitment until the end of year 8

  • Abdominal Ultrasound Screening with serum AFPOther

    abdominal ultrasound (US)+serum alpha fetoprotein (AFP) every 6 months from the time of recruitment until the end of year 8

Study groups in NCT05486572
Study groupRoleWhat they receive
Abdominal Ultrasound Screening with serum AFPActive comparatorabdominal ultrasound (US)+serum alpha fetoprotein (AFP) every 6 months from the time of recruitment until the end of year 8
Receives: Other: Abdominal Ultrasound Screening with serum AFP
Abbreviated Magnetic Resonance Imaging with serum AFPOtherAbdominal aMRI+ serum AFP every 6 months from the time of recruitment until the end of year 8
Receives: Other: Abbreviated Magnetic Resonance Imaging with serum AFP

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Hepatocellular Carcinoma Mortality

    death due to liver cancer

    Measured: 8 years

Secondary outcomes (3)

  1. Stage of Hepatocellular Carcinoma at diagnosis

    Stage of Hepatocellular Carcinoma at time of diagnosis

    Measured: 8 years

  2. Receipt of potentially curative treatments for Hepatocellular Carcinoma

    Receipt of potentially curative treatments for Hepatocellular Carcinoma

    Measured: 8 years

  3. Overall Survival

    overall survival of liver cancer

    Measured: 8 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Aug 2022
  2. Study start3 Nov 2023
  3. Primary completion1 Sep 2030 (estimated)
  4. Study completion1 Sep 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
4,700 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05486572
Sponsor's protocol ID
2023
Acronym
PREMIUM
Status last verified
Jun 2026
First submitted
1 Aug 2022
Last updated
17 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Ioannou GN, Taddei TH, Planeta BM, Huang GD, Weiss NS, Morgan TR, Dominitz JA, Abou-Alfa GK, Bashir MR, Beheshti MV, Singal AG, Moylan CA, Boland RJ, Buchwalder LF, Mehta RL, Hoisington KS, Do NV, Rogal SS, Kaplan DE, Benhammou JN, Su GL, McDonald LM, Dani G, Dunn DP, Chang ST, Onyiuke IY, Sharma A, Kyriakides TC; PREMIUM Study Group. Practice changing RCT design and rationale: Abbreviated MRI plus AFP vs. ultrasound plus AFP for HCC surveillance in cirrhosis (PREMIUM study). JHEP Rep. 2025 Nov 6;8(2):101666. doi: 10.1016/j.jhepr.2025.101666. eCollection 2026 Feb.

    PubMed 41624484

Questions about this trial

What is this clinical trial studying?

A study testing Abbreviated Magnetic Resonance Imaging with serum AFP and Abdominal Ultrasound Screening with serum AFP in people with Carcinoma, Hepatocellular and Cirrhosis, run by VA Office of Research and Development at 34 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 17 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 34 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact George N Ioannou, MD MS ((206) 277-3136, George.Ioannou@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Hepatocellular Carcinoma Mortality (time frame: 8 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05486572, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2026.

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