Cirrhosis of LiverPRIUSNCT01446666
Gadoxetic Acid-MRI Versus Ultrasonography for the Surveillance of Hepatocellular Carcinoma in High-risk Patients
An observational study of Cirrhosis of Liver, run by Asan Medical Center at 1 site in South Korea.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Cirrhosis of Liver
- How many people
- 423 participants
- Where
- 1 siteSouth Korea
- Study dates
- Nov 2011to Dec 2014
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Hospital out-patient clinic
Who may be able to join
- Patients with liver cirrhosis with the 1 year risk of HCC of 5% or higher meeting all of following criteria;
- The evidence of cirrhosis of any etiology within 12 months prior to screening Definition of cirrhosis by any of following methods
- 1) Histologically by liver biopsy;
- 2) Non-histologically by evidence of portal hypertension in the presence of chronic liver disease;
- Evidence of portal hypertension, including any of followings;
- The identification of splenomegaly on USG, CT, or MRI examinations with typical features of cirrhosis
Show all 14Show fewer
- The identification of esophageal or gastric varices on endoscopic examination
- 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).
- Older than 20 years of age
- Absence of previous or current history of HCC
- Absence of HCC should be identified by liver USG, dynamic CT, or contrast-enhanced MRI within 6 months prior to screening
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2
- Patient is able to comply with scheduled visits, evaluation plans, and other study procedures.
- Patient is willing to provide written informed consent
Who cannot join
- Presence of any of following criteria;
- Active or suspected cancer other than HCC, or a history of malignancy where the risk of recurrence is >20% within 2 years
- Child-Pugh score >9
- Significant medical comorbidities in which survival is predicted to be less than 3 years
- Estimated glomerular filtration rate (GFR) < 30 mL/min/1.73m2
- Precautions for MRI (cardiac pacemaker, ferromagnetic implants, etc.)
- Severe claustrophobia that may interfere with protocol compliance.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
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.
Read the detailed description
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.
The 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.
Surveillance 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.
Gadoxetic 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.
Thus, 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.
- Conditions
- Cirrhosis of Liver
- Keywords
- hepatocellular carcinoma, surveillance, gadoxetic acid, MRI
- Medical subject headings
- Fibrosis, Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| HCC high-risk group | Patients with liver cirrhosis with the 1-year risk of HCC of 5% or higher ; 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). |
What is being measured
The primary outcome is the main question the study is designed to answer.
Detection Rate of Patients With HCC
- 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
Measured: during the 1.5-year study period (from the date of first screening to 6 months following the last screening)
Secondary outcomes (4)
Detection Rate of Patients With Early Stage HCC
- 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.
- 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.
Measured: during the 1.5-year study period (from the date of first screening to 6 months following the last screening)
Detection Rate of Patients With Very Early Stage HCC
- 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.
- 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.
Measured: during the 1.5-year study period (from the date of first screening to 6 months following the last screening)
False Positive Rate
The false-positive rate was defined as the number of tests with positive findings by a specific imaging modality in patients without a HCC.
Measured: during the 1.5-year study period (from the date of first screening to 6 months following the last screening)
Positive Predictive Value for HCC
The positive predictive value was the number of true positive test results in patients with the positive tests in a specific modality.
Measured: during the 1.5-year study period (from the date of first screening to 6 months following the last screening)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2011 (estimated)
- Study startNov 2011
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cirrhosis of LiverStudies of the same condition, open and under way.
- More trials run by Asan Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 423 participants (actual)
Sponsor and investigators
- Lead sponsor
- Asan Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Principal investigator, Young-Suk Lim, Asan Medical Center
- Investigators
- Young-Suk Lim, MD, PhD, Principal investigator, Asan Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01446666
- Sponsor's protocol ID
- AMC2011-0587
- Acronym
- PRIUS
- Status last verified
- Jan 2019
- First submitted
- 17 Sep 2011
- Last updated
- 1 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Heo S, Kim SY, Lee SJ, Lee SS, Byun JH, Won HJ, Shin YM, Choi SH, Sirlin CB. LI-RADS Ultrasound Surveillance Version 2024: Comparison With Version 2017 for Hepatocellular Carcinoma Detection and Risk Factors for Visualization Score C. AJR Am J Roentgenol. 2025 Apr;224(4):e2432433. doi: 10.2214/AJR.24.32433. Epub 2025 Jan 22.
PubMed 39840963Kim 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.
PubMed 30365164Kim 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.
PubMed 27657493
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01446666
- Acronym / sponsor ID
- PRIUS / AMC2011-0587
- Conditions
- Cirrhosis of Liver
- Keywords
- hepatocellular carcinoma, surveillance, gadoxetic acid, MRI
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 423 participants (actual)
- Lead sponsor
- Asan Medical CenterUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- Nov 2011
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 5 Oct 2011 (estimated)
- Results
- Posted 14 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
The 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.
Surveillance 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.
Gadoxetic 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.
Thus, 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HCC high-risk group | – | –Patients with liver cirrhosis with the 1-year risk of HCC of 5% or higher ; 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). |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Hospital out-patient clinic
Key inclusion criteria (14 listed)
- Patients with liver cirrhosis with the 1 year risk of HCC of 5% or higher meeting all of following criteria;
- The evidence of cirrhosis of any etiology within 12 months prior to screening Definition of cirrhosis by any of following methods
- 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).
- Older than 20 years of age
- Absence of previous or current history of HCC
Key exclusion criteria (8 listed)
- Presence of any of following criteria;
- Active or suspected cancer other than HCC, or a history of malignancy where the risk of recurrence is >20% within 2 years
- Child-Pugh score >9
- Significant medical comorbidities in which survival is predicted to be less than 3 years
- Estimated glomerular filtration rate (GFR) < 30 mL/min/1.73m2
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Detection Rate of Patients With HCC
Time frame: during the 1.5-year study period (from the date of first screening to 6 months following the last screening)
- 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
4 secondary outcomes
Detection Rate of Patients With Early Stage HCC
Time frame: during the 1.5-year study period (from the date of first screening to 6 months following the last screening)
Detection Rate of Patients With Very Early Stage HCC
Time frame: during the 1.5-year study period (from the date of first screening to 6 months following the last screening)
False Positive Rate
Time frame: during the 1.5-year study period (from the date of first screening to 6 months following the last screening)
Positive Predictive Value for HCC
Time frame: during the 1.5-year study period (from the date of first screening to 6 months following the last screening)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39840963Heo S, Kim SY, Lee SJ, Lee SS, Byun JH, Won HJ, Shin YM, Choi SH, Sirlin CB. LI-RADS Ultrasound Surveillance Version 2024: Comparison With Version 2017 for Hepatocellular Carcinoma Detection and Risk Factors for Visualization Score C. AJR Am J Roentgenol. 2025 Apr;224(4):e2432433. doi: 10.2214/AJR.24.32433. Epub 2025 Jan 22.
- Derived from this study: PubMed 30365164Kim 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.
- Derived from this study: PubMed 27657493Kim 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Young-Suk Lim, MD, PhD principal investigator
Asan Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cirrhosis of Liver, run by Asan Medical Center at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Detection Rate of Patients With HCC (time frame: during the 1.5-year study period (from the date of first screening to 6 months following the last screening)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01446666, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2019.