Brief 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 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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

4,700

participants targeted

Target at P75+ for not_applicable

Timeline

64mo left

Started Nov 2023

Longer than P75 for not_applicable

Geographic Reach

1 country

32 active sites

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

7.8 years study duration

Study Progress32%

Nov 2023Sep 2031

First Submitted

Initial submission to the registry

August 1, 2022

Completed

2 days until next milestone

First Posted

Study publicly available on registry

August 3, 2022

Completed

1.3 years until next milestone

Study Start

First participant enrolled

November 3, 2023

Completed

6.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2030

Expected

1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2031

Last Updated

April 21, 2026

Status Verified

April 1, 2026

Enrollment Period

6.8 years

First QC Date

August 1, 2022

Last Update Submit

April 15, 2026

Conditions

Carcinoma, Hepatocellular Cirrhosis

Keywords

hepatic, oncologyliverchronic diseases; health services and systemsprospective, randomized, clinical trialmagnetic resonance imaging; ultrasonographycirrhosis; liver cancer

Outcome Measures

Primary Outcomes (1)

Hepatocellular Carcinoma Mortality
death due to liver cancer
8 years

Secondary Outcomes (3)

Stage of Hepatocellular Carcinoma at diagnosis
8 years
Receipt of potentially curative treatments for Hepatocellular Carcinoma
8 years
Overall Survival
8 years

Study Arms (2)

Abdominal Ultrasound Screening with serum AFP

ACTIVE COMPARATOR

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

Abbreviated Magnetic Resonance Imaging with serum AFP

OTHER

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

Interventions

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

Abbreviated Magnetic Resonance Imaging with serum AFP

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

Abdominal Ultrasound Screening with serum AFP

Eligibility Criteria

Age18 Years - 75 Years

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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:
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

You may not qualify if:

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
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)
+8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

VA Office of Research and Developmentlead

Study Sites (32)

Birmingham VA Medical Center, Birmingham, AL

Birmingham, Alabama, 35233-1927, United States

RECRUITING

Southern Arizona VA Health Care System, Tucson, AZ

Tucson, Arizona, 85723-0001, United States

RECRUITING

Central Arkansas Veterans Healthcare System , Little Rock, AR

Little Rock, Arkansas, 72205, United States

RECRUITING

VA Long Beach Healthcare System, Long Beach, CA

Long Beach, California, 90822, United States

RECRUITING

VA Palo Alto Health Care System, Palo Alto, CA

Palo Alto, California, 94304-1207, United States

RECRUITING

VA Northern California Health Care System, Mather, CA

Sacramento, California, 95655-4200, United States

RECRUITING

VA San Diego Healthcare System, San Diego, CA

San Diego, California, 92161-0002, United States

RECRUITING

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

West Los Angeles, California, 90073-1003, United States

RECRUITING

Rocky Mountain Regional VA Medical Center, Aurora, CO

Aurora, Colorado, 80045-7211, United States

RECRUITING

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

West Haven, Connecticut, 06516-2770, United States

RECRUITING

Washington DC VA Medical Center, Washington, DC

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

RECRUITING

Miami VA Healthcare System, Miami, FL

Miami, Florida, 33125, United States

RECRUITING

James A. Haley Veterans' Hospital, Tampa, FL

Tampa, Florida, 33612, United States

ACTIVE NOT RECRUITING

Atlanta VA Medical and Rehab Center, Decatur, GA

Decatur, Georgia, 30033-4004, United States

RECRUITING

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

Baltimore, Maryland, 21201, United States

RECRUITING

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

Boston, Massachusetts, 02130-4817, United States

RECRUITING

VA Ann Arbor Healthcare System, Ann Arbor, MI

Ann Arbor, Michigan, 48105-2303, United States

RECRUITING

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

St Louis, Missouri, 63106-1621, United States

RECRUITING

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

Omaha, Nebraska, 68105-1850, United States

RECRUITING

VA NY Harbor Healthcare System, New York, NY

New York, New York, 10010-5011, United States

RECRUITING

James J. Peters VA Medical Center, Bronx, NY

The Bronx, New York, 10468-3904, United States

RECRUITING

Durham VA Medical Center, Durham, NC

Durham, North Carolina, 27705-3875, United States

RECRUITING

Louis Stokes VA Medical Center, Cleveland, OH

Cleveland, Ohio, 44106-1702, United States

RECRUITING

VA Portland Health Care System, Portland, OR

Portland, Oregon, 97207-2964, United States

RECRUITING

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

Philadelphia, Pennsylvania, 19104-4551, United States

RECRUITING

Ralph H. Johnson VA Medical Center, Charleston, SC

Charleston, South Carolina, 29401-5703, United States

RECRUITING

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

Columbia, South Carolina, 29209-1638, United States

RECRUITING

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

Dallas, Texas, 75216-7167, United States

RECRUITING

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, 77030-4211, United States

RECRUITING

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

Salt Lake City, Utah, 84148-0001, United States

RECRUITING

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

Seattle, Washington, 98108-1532, United States

RECRUITING

William S. Middleton Memorial Veterans Hospital, Madison, WI

Madison, Wisconsin, 53705-2254, United States

RECRUITING

Related Publications (1)

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.
PMID: 41624484DERIVED

MeSH Terms

Conditions

Carcinoma, HepatocellularFibrosisNeoplasmsChronic DiseaseLiver Neoplasms

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver DiseasesPathologic ProcessesPathological Conditions, Signs and SymptomsDisease Attributes

Study Officials

George N. Ioannou, MD MS
VA Puget Sound Health Care System Seattle Division, Seattle, WA
STUDY CHAIR

Central Study Contacts

George N Ioannou, MD MS

CONTACT

(206) 277-3136 George.Ioannou@va.gov

Study Design

Study Type: interventional
Phase: not applicable
Allocation: RANDOMIZED
Masking: NONE
Purpose: PREVENTION
Intervention Model: PARALLEL
Sponsor Type: FED
Responsible Party: SPONSOR

Study Record Dates

First Submitted

August 1, 2022

First Posted

August 3, 2022

Study Start

November 3, 2023

Primary Completion (Estimated)

September 1, 2030

Study Completion (Estimated)

September 1, 2031

Last Updated

April 21, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing: Will not share

Locations

US(32)

Brief Summary

Trial Health

Trial Health Score

Trial Relationships

Related Scientific Literature

Study Timeline

First Submitted

First Posted

Study Start

Primary Completion

Study Completion

Conditions

Keywords

Outcome Measures

Primary Outcomes (1)

Secondary Outcomes (3)

Study Arms (2)

Abdominal Ultrasound Screening with serum AFP

Abbreviated Magnetic Resonance Imaging with serum AFP

Interventions

Eligibility Criteria

You may qualify if:

You may not qualify if:

Sponsors & Collaborators

Study Sites (32)

Related Publications (1)

MeSH Terms

Conditions

Condition Hierarchy (Ancestors)

Study Officials

Central Study Contacts

Study Design

Study Record Dates

Data Sharing

Locations