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