Preventing Liver Cancer Mortality Through Imaging With Ultrasound vs. MRI — PREMIUM  

Cirrhosis Clinical Trial

Official title: CSP #2023 - Preventing Liver Cancer Mortality Through Imaging With Ultrasound vs. MRI (The PREMIUM Study)

Status Recruiting

Clinical 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 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Cirrhosis
• Fibrosis
• Liver Neoplasms

• NCT number: NCT05486572
• Study type: Interventional
• Source: VA Office of Research and Development
• Contact: George N Ioannou, MD MS
• Phone: (206) 277-3136
• Email: George.Ioannou@va.gov
• Status: Recruiting
• Phase: N/A
• Start date: November 3, 2023
• Completion date: September 1, 2031