Preventing Liver Cancer Mortality Through Imaging With Ultrasound vs. MRI

NCT ID: NCT05486572

Last Updated: 2025-09-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

4700 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-11-03

Study Completion Date

2031-09-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Carcinoma, Hepatocellular Cirrhosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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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

Group Type ACTIVE_COMPARATOR

Abdominal Ultrasound Screening with serum AFP

Intervention Type OTHER

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

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

Group Type OTHER

Abbreviated Magnetic Resonance Imaging with serum AFP

Intervention Type OTHER

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

Interventions

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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

Intervention Type 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

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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VA Office of Research and Development

FED

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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George N. Ioannou, MD MS

Role: STUDY_CHAIR

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

Locations

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VA Long Beach Healthcare System, Long Beach, CA

Long Beach, California, United States

Site Status RECRUITING

VA Palo Alto Health Care System, Palo Alto, CA

Palo Alto, California, United States

Site Status RECRUITING

VA Northern California Health Care System, Mather, CA

Sacramento, California, United States

Site Status RECRUITING

VA San Diego Healthcare System, San Diego, CA

San Diego, California, United States

Site Status RECRUITING

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

West Los Angeles, California, United States

Site Status RECRUITING

Rocky Mountain Regional VA Medical Center, Aurora, CO

Aurora, Colorado, United States

Site Status RECRUITING

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

West Haven, Connecticut, United States

Site Status RECRUITING

James A. Haley Veterans' Hospital, Tampa, FL

Tampa, Florida, United States

Site Status ACTIVE_NOT_RECRUITING

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

Boston, Massachusetts, United States

Site Status RECRUITING

VA Ann Arbor Healthcare System, Ann Arbor, MI

Ann Arbor, Michigan, United States

Site Status RECRUITING

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

Omaha, Nebraska, United States

Site Status RECRUITING

James J. Peters VA Medical Center, Bronx, NY

The Bronx, New York, United States

Site Status RECRUITING

Louis Stokes VA Medical Center, Cleveland, OH

Cleveland, Ohio, United States

Site Status RECRUITING

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

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, United States

Site Status RECRUITING

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

Seattle, Washington, United States

Site Status RECRUITING

William S. Middleton Memorial Veterans Hospital, Madison, WI

Madison, Wisconsin, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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George N Ioannou, MD MS

Role: CONTACT

(206) 277-3136

Facility Contacts

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Morgan R Timothy, MD

Role: primary

Cheung Ramsey, MD

Role: primary

650-493-5000

Anthony Albanese, MD

Role: primary

Heather Patton, MD

Role: primary

858-260-0190

Joseph Pisegna, MD

Role: primary

Ashley M Lane, MD

Role: primary

720-723-6773

Sofia Jakab, MD

Role: primary

Gyorgy Baffy, MD

Role: primary

Grace L Su, MD

Role: primary

Peter Mannon, MD

Role: primary

Tae H Lee, MD

Role: primary

718-584-9000 ext. 3600

Percia Davitkav, MD

Role: primary

David Kaplan, MD

Role: primary

Ruben Hernaez, MD

Role: primary

George N Ioannou, MD MS

Role: primary

206-277-3136

Adnan Said, MD

Role: primary

Other Identifiers

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2023

Identifier Type: -

Identifier Source: org_study_id

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