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Trial Title: Preventing Liver Cancer Mortality Through Imaging With Ultrasound vs. MRI

NCT ID: NCT05486572

Condition: Carcinoma, Hepatocellular
Cirrhosis

Conditions: Official terms:
Liver Neoplasms
Carcinoma, Hepatocellular
Fibrosis

Conditions: Keywords:
hepatic, oncology
liver
chronic diseases; health services and systems
prospective, randomized, clinical trial
magnetic resonance imaging; ultrasonography
cirrhosis; liver cancer

Study type: Interventional

Study phase: N/A

Overall status: Recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Prevention

Masking: None (Open Label)

Intervention:

Intervention type: Other
Intervention name: Abbreviated Magnetic Resonance Imaging with serum AFP
Description: Abdominal aMRI+ serum AFP every 6 months from the time of recruitment until the end of year 8
Arm group label: Abbreviated Magnetic Resonance Imaging with serum AFP

Intervention type: Other
Intervention name: Abdominal Ultrasound Screening with serum AFP
Description: abdominal ultrasound (US)+serum alpha fetoprotein (AFP) every 6 months from the time of recruitment until the end of year 8
Arm group label: Abdominal Ultrasound Screening with serum AFP

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.

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.

Criteria for eligibility:
Criteria:
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

Gender: All

Minimum age: 18 Years

Maximum age: 75 Years

Healthy volunteers: No

Locations:

Facility:
Name: VA Long Beach Healthcare System, Long Beach, CA

Address:
City: Long Beach
Zip: 90822
Country: United States

Status: Recruiting

Contact:
Last name: Morgan R Timothy, MD
Email: morgan.timothy@va.gov

Facility:
Name: VA Palo Alto Health Care System, Palo Alto, CA

Address:
City: Palo Alto
Zip: 94304-1207
Country: United States

Status: Recruiting

Contact:
Last name: Cheung Ramsey, MD

Phone: 650-493-5000
Email: ramsey.cheung@va.gov

Facility:
Name: VA Northern California Health Care System, Mather, CA

Address:
City: Sacramento
Zip: 95655-4200
Country: United States

Status: Recruiting

Contact:
Last name: Anthony Albanese, MD
Email: anthony.albanese@va.gov

Facility:
Name: VA San Diego Healthcare System, San Diego, CA

Address:
City: San Diego
Zip: 92161-0002
Country: United States

Status: Recruiting

Contact:
Last name: Heather Patton, MD

Phone: 858-260-0190

Facility:
Name: VA Greater Los Angeles Healthcare System, West Los Angeles, CA

Address:
City: West Los Angeles
Zip: 90073-1003
Country: United States

Status: Recruiting

Contact:
Last name: Joseph Pisegna, MD
Email: joseph.pisegna@va.gov

Facility:
Name: Rocky Mountain Regional VA Medical Center, Aurora, CO

Address:
City: Aurora
Zip: 80045-7211
Country: United States

Status: Recruiting

Contact:
Last name: Ashley M Lane, MD

Phone: 720-723-6773
Email: ashley.lane6@va.gov

Facility:
Name: VA Connecticut Healthcare System West Haven Campus, West Haven, CT

Address:
City: West Haven
Zip: 06516-2770
Country: United States

Status: Recruiting

Contact:
Last name: Sofia Jakab, MD
Email: sofia.jakab@va.gov

Facility:
Name: James A. Haley Veterans' Hospital, Tampa, FL

Address:
City: Tampa
Zip: 33612
Country: United States

Status: Recruiting

Contact:
Last name: Prasad Kalkarni, MD
Email: prasad.kalkarni@va.gov

Facility:
Name: VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Address:
City: Boston
Zip: 02130-4817
Country: United States

Status: Recruiting

Contact:
Last name: Gyorgy Baffy, MD
Email: gyorgy.baffy@va.gov

Facility:
Name: VA Ann Arbor Healthcare System, Ann Arbor, MI

Address:
City: Ann Arbor
Zip: 48105-2303
Country: United States

Status: Recruiting

Contact:
Last name: Grace L Su, MD
Email: grace.su@va.gov

Facility:
Name: James J. Peters VA Medical Center, Bronx, NY

Address:
City: Bronx
Zip: 10468-3904
Country: United States

Status: Recruiting

Contact:
Last name: Tae H Lee, MD

Phone: 718-584-9000

Phone ext: 3600
Email: tae.lee@va.gov

Facility:
Name: Louis Stokes VA Medical Center, Cleveland, OH

Address:
City: Cleveland
Zip: 44106-1702
Country: United States

Status: Recruiting

Contact:
Last name: Percia Davitkav, MD
Email: percia.davitkov@va.gov

Facility:
Name: Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

Address:
City: Philadelphia
Zip: 19104-4551
Country: United States

Status: Recruiting

Contact:
Last name: David Kaplan, MD
Email: david.kaplan@va.gov

Facility:
Name: Michael E. DeBakey VA Medical Center, Houston, TX

Address:
City: Houston
Zip: 77030-4211
Country: United States

Status: Recruiting

Contact:
Last name: Ruben Hernaez, MD
Email: ruben.hernaez@va.gov

Facility:
Name: VA Puget Sound Health Care System Seattle Division, Seattle, WA

Address:
City: Seattle
Zip: 98108-1532
Country: United States

Status: Recruiting

Contact:
Last name: George N Ioannou, MD MS

Phone: 206-277-3136
Email: George.Ioannou@va.gov

Investigator:
Last name: George N. Ioannou, MD MS
Email: Study Chair

Facility:
Name: William S. Middleton Memorial Veterans Hospital, Madison, WI

Address:
City: Madison
Zip: 53705-2254
Country: United States

Status: Recruiting

Contact:
Last name: Adnan Said, MD
Email: adam.said@va.gov

Start date: November 3, 2023

Completion date: September 1, 2031

Lead sponsor:
Agency: VA Office of Research and Development
Agency class: U.S. Fed

Source: VA Office of Research and Development

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05486572

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