Ignite Creation Date:
2025-12-24 @ 4:19 PM
Ignite Modification Date:
2025-12-26 @ 11:45 PM
Study NCT ID:
NCT01446666
Status:
COMPLETED
Last Update Posted:
2019-02-01
First Post:
2011-09-17
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Gadoxetic Acid-MRI Versus Ultrasonography for the Surveillance of Hepatocellular Carcinoma in High-risk Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D005355', 'term': 'Fibrosis'}, {'id': 'D006528', 'term': 'Carcinoma, Hepatocellular'}], 'ancestors': [{'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D000230', 'term': 'Adenocarcinoma'}, {'id': 'D002277', 'term': 'Carcinoma'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D008113', 'term': 'Liver Neoplasms'}, {'id': 'D004067', 'term': 'Digestive System Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D008107', 'term': 'Liver Diseases'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'limys@amc.seoul.kr', 'phone': '+82-02-3010-5933', 'title': 'Professor Young-Suk Lim', 'organization': 'Asan Medical Center, University of Ulsan College of Medicine'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'US+MRI', 'description': 'The patients were evaluated by three rounds of screening tests with paired US and gadoxetic acid-enhanced MRI at 6-month intervals', 'otherNumAtRisk': 407, 'otherNumAffected': 0, 'seriousNumAtRisk': 407, 'seriousNumAffected': 0}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Detection Rate of Patients With HCC', 'denoms': [{'units': 'Participants', 'counts': [{'value': '43', 'groupId': 'OG000'}, {'value': '43', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ultasonography', 'description': 'Results from ultrasonography'}, {'id': 'OG001', 'title': 'Gadoxetic Acid-enhanced MRI', 'description': 'Results from Gadoxetic acid-enhanced MRI'}], 'classes': [{'categories': [{'measurements': [{'value': '27.9', 'groupId': 'OG000'}, {'value': '86.0', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<0.01', 'groupIds': ['OG000', 'OG001'], 'groupDescription': 'The HCC detection rate was defined as the number of patients with HCC detected by a given modality divided by the total number of patients with HCC detected by all modalities and by follow-up dynamic CT scan. The HCC detection rates from ultrasonography and MRI were compared.', 'statisticalMethod': 'McNemar', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'NUMBER', 'timeFrame': 'during the 1.5-year study period (from the date of first screening to 6 months following the last screening)', 'description': '\\- The number of patients with definite HCC detected by a given modality divided by the total number of patients with definite HCC detected by any of 2 modalities plus interval cancers', 'unitOfMeasure': 'percentage of HCC detected on each exam', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Detection Rate of Patients With Early Stage HCC', 'denoms': [{'units': 'Participants', 'counts': [{'value': '42', 'groupId': 'OG000'}, {'value': '42', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ultasonography', 'description': 'Results from ultrasonography'}, {'id': 'OG001', 'title': 'Gadoxetic Acid-enhanced MRI', 'description': 'Results from Gadoxetic acid-enhanced MRI'}], 'classes': [{'categories': [{'measurements': [{'value': '26.2', 'groupId': 'OG000'}, {'value': '85.7', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<0.01', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'McNemar', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'NUMBER', 'timeFrame': 'during the 1.5-year study period (from the date of first screening to 6 months following the last screening)', 'description': '* The number of patients with early stage HCC detected by a given modality divided by the total number of patients with early stage HCC detected by any of 2 modalities plus interval cancers.\n* Early stage (stage A or 0) HCC is defined by the Barcelona Clinic Liver Cancer staging system (BCLC): A single HCC \\<5 cm or \\<=3 lesions each \\<3 cm in diameter, without gross vascular invasion or extrahepatic metastasis.', 'unitOfMeasure': 'percentage of early HCC detected', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Detection Rate of Patients With Very Early Stage HCC', 'denoms': [{'units': 'Participants', 'counts': [{'value': '32', 'groupId': 'OG000'}, {'value': '32', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ultasonography', 'description': 'Results from ultrasonography'}, {'id': 'OG001', 'title': 'Gadoxetic Acid-enhanced MRI', 'description': 'Results from Gadoxetic acid-enhanced MRI'}], 'classes': [{'categories': [{'measurements': [{'value': '27.3', 'groupId': 'OG000'}, {'value': '84.8', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<0.01', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'McNemar', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'NUMBER', 'timeFrame': 'during the 1.5-year study period (from the date of first screening to 6 months following the last screening)', 'description': '* The number of patients with HCC nodules of very early stage detected by a given modality divided by the total number of definite HCC nodules of very early stage detected by any of 2 modalities plus interval cancers.\n* Very early stage (stage 0) HCC is defined by the Barcelona Clinic Liver Cancer staging system (BCLC): A single HCC \\<2 cm without gross vascular invasion or extrahepatic metastasis.', 'unitOfMeasure': 'percentage of detected very early HCC', 'reportingStatus': 'POSTED', 'populationDescription': 'Of the 43 patients, 32 (74.4%) had very early-stage.'}, {'type': 'SECONDARY', 'title': 'False Positive Rate', 'denoms': [{'units': 'Participants', 'counts': [{'value': '364', 'groupId': 'OG000'}, {'value': '364', 'groupId': 'OG001'}]}, {'units': 'the number of exams', 'counts': [{'value': '1057', 'groupId': 'OG000'}, {'value': '1057', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ultasonography', 'description': 'Results from ultrasonography'}, {'id': 'OG001', 'title': 'Gadoxetic Acid-enhanced MRI', 'description': 'Results from Gadoxetic acid-enhanced MRI'}], 'classes': [{'categories': [{'measurements': [{'value': '5.6', 'groupId': 'OG000'}, {'value': '3.0', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.004', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'McNemar', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'NUMBER', 'timeFrame': 'during the 1.5-year study period (from the date of first screening to 6 months following the last screening)', 'description': 'The false-positive rate was defined as the number of tests with positive findings by a specific imaging modality in patients without a HCC.', 'unitOfMeasure': 'percentage of false positive test', 'reportingStatus': 'POSTED', 'typeUnitsAnalyzed': 'the number of exams', 'denomUnitsSelected': 'the number of exams'}, {'type': 'SECONDARY', 'title': 'Positive Predictive Value for HCC', 'denoms': [{'units': 'Participants', 'counts': [{'value': '71', 'groupId': 'OG000'}, {'value': '69', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ultasonography', 'description': 'Results from ultrasonography'}, {'id': 'OG001', 'title': 'Gadoxetic Acid-enhanced MRI', 'description': 'Results from Gadoxetic acid-enhanced MRI'}], 'classes': [{'categories': [{'measurements': [{'value': '16.9', 'groupId': 'OG000'}, {'value': '53.6', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'during the 1.5-year study period (from the date of first screening to 6 months following the last screening)', 'description': 'The positive predictive value was the number of true positive test results in patients with the positive tests in a specific modality.', 'unitOfMeasure': 'percentage of true positive calls', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'US+MRI', 'description': 'The patients were evaluated by three rounds of screening tests with paired US and gadoxetic acid-enhanced MRI at 6-month intervals'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'comment': 'Among the 423 participants who consented, 15 withdrew the consent and one died.', 'groupId': 'FG000', 'numSubjects': '407'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '326'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '81'}]}]}], 'recruitmentDetails': 'Study participants were recruited between November 2011 and August 2012. The inclusion criteria for participation were an age of 20 years or older and the presence of cirrhosis with an estimated annual HCC risk of \\>5%.', 'preAssignmentDetails': 'The absence of hepatocellular carcinoma (HCC) had been evaluated by US, dynamic CT scan, or MRI within 6 months before enrollment. Patients with Child-Pugh class C liver function or estimated glomerular filtration rate \\<30 mL/min/1.73m\\^2 were excluded.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '407', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'US+MRI', 'description': 'The patients were evaluated by three rounds of screening tests with paired US and gadoxetic acid-enhanced MRI at 6-month intervals.'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '56', 'groupId': 'BG000', 'lowerLimit': '52', 'upperLimit': '62'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'years', 'dispersionType': 'INTER_QUARTILE_RANGE'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '177', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '230', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race/Ethnicity, Customized', 'classes': [{'title': 'Korean', 'categories': [{'measurements': [{'value': '407', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'South Korea', 'categories': [{'measurements': [{'value': '407', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Buffy coat and serum'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 423}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2011-11'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-01', 'completionDateStruct': {'date': '2014-12', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2019-01-12', 'studyFirstSubmitDate': '2011-09-17', 'resultsFirstSubmitDate': '2017-07-02', 'studyFirstSubmitQcDate': '2011-10-03', 'lastUpdatePostDateStruct': {'date': '2019-02-01', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2018-07-18', 'studyFirstPostDateStruct': {'date': '2011-10-05', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2019-01-14', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2014-12', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Detection Rate of Patients With HCC', 'timeFrame': 'during the 1.5-year study period (from the date of first screening to 6 months following the last screening)', 'description': '\\- The number of patients with definite HCC detected by a given modality divided by the total number of patients with definite HCC detected by any of 2 modalities plus interval cancers'}], 'secondaryOutcomes': [{'measure': 'Detection Rate of Patients With Early Stage HCC', 'timeFrame': 'during the 1.5-year study period (from the date of first screening to 6 months following the last screening)', 'description': '* The number of patients with early stage HCC detected by a given modality divided by the total number of patients with early stage HCC detected by any of 2 modalities plus interval cancers.\n* Early stage (stage A or 0) HCC is defined by the Barcelona Clinic Liver Cancer staging system (BCLC): A single HCC \\<5 cm or \\<=3 lesions each \\<3 cm in diameter, without gross vascular invasion or extrahepatic metastasis.'}, {'measure': 'Detection Rate of Patients With Very Early Stage HCC', 'timeFrame': 'during the 1.5-year study period (from the date of first screening to 6 months following the last screening)', 'description': '* The number of patients with HCC nodules of very early stage detected by a given modality divided by the total number of definite HCC nodules of very early stage detected by any of 2 modalities plus interval cancers.\n* Very early stage (stage 0) HCC is defined by the Barcelona Clinic Liver Cancer staging system (BCLC): A single HCC \\<2 cm without gross vascular invasion or extrahepatic metastasis.'}, {'measure': 'False Positive Rate', 'timeFrame': 'during the 1.5-year study period (from the date of first screening to 6 months following the last screening)', 'description': 'The false-positive rate was defined as the number of tests with positive findings by a specific imaging modality in patients without a HCC.'}, {'measure': 'Positive Predictive Value for HCC', 'timeFrame': 'during the 1.5-year study period (from the date of first screening to 6 months following the last screening)', 'description': 'The positive predictive value was the number of true positive test results in patients with the positive tests in a specific modality.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['hepatocellular carcinoma', 'surveillance', 'gadoxetic acid', 'MRI'], 'conditions': ['Cirrhosis of Liver']}, 'referencesModule': {'references': [{'pmid': '30365164', 'type': 'DERIVED', 'citation': 'Kim HL, An J, Park JA, Park SH, Lim YS, Lee EK. Magnetic Resonance Imaging Is Cost-Effective for Hepatocellular Carcinoma Surveillance in High-Risk Patients With Cirrhosis. Hepatology. 2019 Apr;69(4):1599-1613. doi: 10.1002/hep.30330. Epub 2019 Feb 25.'}, {'pmid': '27657493', 'type': 'DERIVED', 'citation': 'Kim SY, An J, Lim YS, Han S, Lee JY, Byun JH, Won HJ, Lee SJ, Lee HC, Lee YS. MRI With Liver-Specific Contrast for Surveillance of Patients With Cirrhosis at High Risk of Hepatocellular Carcinoma. JAMA Oncol. 2017 Apr 1;3(4):456-463. doi: 10.1001/jamaoncol.2016.3147.'}]}, 'descriptionModule': {'briefSummary': 'Current practice guidelines recommend surveillance for hepatocellular carcinoma (HCC) in liver cirrhosis patients with ultrasonography (USG) every 6 months. However, with the advancement of cirrhosis, the sensitivity of USG decreases, while the risk for HCC increases. Gadoxetic acid (Primovist®)-enhanced magnetic resonance imaging (MRI) has been demonstrated to be of clinical value for diagnosis of HCC with the detection sensitivity of 90-95%, which is significantly higher than USG. The hypothesis to be proved by this study is as follows; Primovist-MRI should show significantly higher sensitivity compared to USG for the detection of early stage HCC when both of these imaging modalities are used with the interval of 6 months in patients with cirrhosis at high risk of developing HCC.', 'detailedDescription': 'Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer-related deaths worldwide. Cirrhosis, particularly when related to viral hepatitis, is the most notable risk factor for HCC and is found in nearly 80-90% of cases.\n\nThe stage of disease at the time of diagnosis largely determines the effectiveness of treatment. The treatment of advanced HCC continues to be primarily palliative, with curative options only available for early HCC. Unfortunately, less than 30% of patients are diagnosed early enough to meet criteria for resection, transplantation, or local ablation.\n\nSurveillance strives to detect HCC at an early stage when it is amenable to curative therapy to reduce mortality. Current practice guidelines recommend surveillance of cirrhotic patients with ultrasonography (USG) every 6 months. However, USG has been reported to have a sensitivity of between 65% and 80% when used as a screening test. However, with the advancement of cirrhosis, the sensitivity of USG decreases, while the risk for HCC increases.\n\nGadoxetic acid (Primovist®)-enhanced magnetic resonance imaging (MRI) of the liver has been demonstrated to be of clinical value for local staging before HCC surgery and for the assessment of patients with inconclusive conventional imaging findings. The detection sensitivity of Primovist-MRI has been known to be as high as 90-95%, which is significantly higher than USG or multiphase computer tomography (CT) scan. MRI does not have radiation exposure, which is a meaningful merit to be used as a surveillance test. However, MRI has never been considered for surveillance or screening of HCC.\n\nThus, the hypothesis to be proved by this study is as follows; Primovist-MRI should show significantly higher sensitivity compared to USG for the detection of early stage HCC when both of these imaging modalities are used with the interval of 6 months in patients with cirrhosis at high risk of developing HCC. The investigators will also analyze whether the specificity of Primovist-MRI are not compromised by its high sensitivity.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '20 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Hospital out-patient clinic', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\nPatients with liver cirrhosis with the 1 year risk of HCC of 5% or higher meeting all of following criteria;\n\n1. The evidence of cirrhosis of any etiology within 12 months prior to screening Definition of cirrhosis by any of following methods\n\n * 1\\) Histologically by liver biopsy;\n * 2\\) Non-histologically by evidence of portal hypertension in the presence of chronic liver disease;\n\n * Evidence of portal hypertension, including any of followings;\n\n 1. The identification of splenomegaly on USG, CT, or MRI examinations with typical features of cirrhosis\n 2. The identification of esophageal or gastric varices on endoscopic examination\n2. High Risk Index (\\>=2.33); Risk Index = 1.65 (if the prothrombin activity is \\<=75%) + 1.41 (if the age is 50 years or older) + 0.92 (if the platelet count is \\<=100x10(3)/mm3) + 0.74 (if the presence of anti-hepatitis C virus \\[HCV\\] or hepatitis B surface antigen \\[HBsAg\\] is positive).\n3. Older than 20 years of age\n4. Absence of previous or current history of HCC\n5. Absence of HCC should be identified by liver USG, dynamic CT, or contrast-enhanced MRI within 6 months prior to screening\n6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2\n7. Patient is able to comply with scheduled visits, evaluation plans, and other study procedures.\n8. Patient is willing to provide written informed consent\n\nExclusion Criteria:\n\nPresence of any of following criteria;\n\n1. Active or suspected cancer other than HCC, or a history of malignancy where the risk of recurrence is \\>20% within 2 years\n2. Child-Pugh score \\>9\n3. Significant medical comorbidities in which survival is predicted to be less than 3 years\n4. Estimated glomerular filtration rate (GFR) \\< 30 mL/min/1.73m2\n5. Precautions for MRI (cardiac pacemaker, ferromagnetic implants, etc.)\n6. Severe claustrophobia that may interfere with protocol compliance.\n7. Any other condition which, in the opinion of the Investigator, would make the patient unsuitable for enrollment or could interfere with the completing the study.'}, 'identificationModule': {'nctId': 'NCT01446666', 'acronym': 'PRIUS', 'briefTitle': 'Gadoxetic Acid-MRI Versus Ultrasonography for the Surveillance of Hepatocellular Carcinoma in High-risk Patients', 'organization': {'class': 'OTHER', 'fullName': 'Asan Medical Center'}, 'officialTitle': 'A Prospective Intra-individual Cohort Study to Compare Gadoxetic Acid (Primovist®)-Enhanced Magnetic Resonance Image and Ultrasonography for the Surveillance of Early Stage Hepatocellular Carcinoma in Patients at High-risk', 'orgStudyIdInfo': {'id': 'AMC2011-0587'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'HCC high-risk group', 'description': 'Patients with liver cirrhosis with the 1-year risk of HCC of 5% or higher\n\n; High Risk Index (\\>=2.33)\n\nRisk Index = 1.65 (if the prothrombin activity is \\<=75%) + 1.41 (if the age is 50 years or older) + 0.92 (if the platelet count is \\<=100x10(3)/mm3) + 0.74 (if the presence of anti-hepatitis C virus \\[HCV\\] or hepatitis B surface antigen \\[HBsAg\\] is positive).'}]}, 'contactsLocationsModule': {'locations': [{'zip': '135-837', 'city': 'Seoul', 'country': 'South Korea', 'facility': 'Asan Medical Center', 'geoPoint': {'lat': 37.566, 'lon': 126.9784}}], 'overallOfficials': [{'name': 'Young-Suk Lim, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Asan Medical Center'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Asan Medical Center', 'class': 'OTHER'}, 'collaborators': [{'name': 'Bayer', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Young-Suk Lim', 'investigatorAffiliation': 'Asan Medical Center'}}}}