CSP #2023 - Preventing Liver Cancer Mortality Through Imaging With Ultrasound vs. MRI (The PREMIUM Study)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 4,700
- 试验地点
- 51
- 主要终点
- Hepatocellular Carcinoma Mortality
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
- •Able to provide informed consent
排除标准
- •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
- •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)
- •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
- •Inability to complete planned study visits (e.g. lives too far from VA, no transportation, etc.)
- •Currently pregnant
研究组 & 干预措施
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
干预措施: Abdominal Ultrasound Screening with serum AFP (Other)
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
干预措施: Abbreviated Magnetic Resonance Imaging with serum AFP (Other)
结局指标
主要结局
Hepatocellular Carcinoma Mortality
时间窗: 8 years
death due to liver cancer
次要结局
- Stage of Hepatocellular Carcinoma at diagnosis(8 years)
- Overall Survival(8 years)
- Receipt of potentially curative treatments for Hepatocellular Carcinoma(8 years)