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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04455932

Registration number

NCT04455932

Ethics application status

Date submitted

27/06/2020

Date registered

2/07/2020

Titles & IDs

Public title

HCC Surveillance: Comparison of Abbreviated Non-contrast MRI and Ultrasound Surveillance in Cirrhotic Patients With Suboptimal Ultrasound Visualisation

Scientific title

HCC Surveillance: Comparison of Abbreviated Non-contrast MRI and Ultrasound Surveillance in Cirrhotic Patients With Suboptimal Ultrasound Visualisation

Secondary ID [1]

2019/PID15472

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Hepatocellular Carcinoma

HCC

Condition category

Condition code

Cancer

Liver

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Diagnosis / Prognosis - Abbreviated non-contrast MRI of the liver
Diagnosis / Prognosis - Ultrasound surveillance
Diagnosis / Prognosis - Multiphase contrast-enhanced liver MRI

Experimental: HCC surveillance with US and aNC-MRI -

Diagnosis / Prognosis: Abbreviated non-contrast MRI of the liver
every 6 months

Diagnosis / Prognosis: Ultrasound surveillance
every 6 months

Diagnosis / Prognosis: Multiphase contrast-enhanced liver MRI
screening

Intervention code [1]

Diagnosis / Prognosis

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

HCC detection with US surveillance versus aNC-MRI surveillance

Timepoint [1]

3 or 5 years

Eligibility

Key inclusion criteria

Inclusion criteria

* Patients with cirrhosis (all causes of cirrhosis, except obscure causes such as vascular or congenital fibrosis) AND reduced visualisation of their liver on ultrasound (vB and vC).
* The criteria of cirrhosis can be obtained with any of the following methods:

1. Histologically by liver biopsy
2. Past signs of decompensated liver disease such as ascites, encephalopathy, varices or bacterial peritonitis
3. Clinically suspicion of cirrhosis PLUS one of the following:

1. Radiological evidence of morphologic changes of the liver and evidence of portal hypertension on US, CT or MRI examinations, including the identification of hepatic surface nodularity, splenomegaly, portal collaterals, varices and ascites
2. Fibroscan (transient elastography) median liver stiffness >12.5 kPa, the Fibroscan must be performed by an experienced technician and interpreted by the hepatologist
3. Platelet count <100 (x10^9/L) with no alternative cause
* Absence of previous history or current suspicion of HCC - Absence of HCC is defined by liver US, multiphase CT or contrast-enhanced MRI within 6 months prior to surveillance
* Patient is able to comply with scheduled visits, evaluation plans and other study procedures in the opinion of the investigator
* Patient is willing to provide written informed consent

Minimum age

20 Years

Maximum age

85 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Exclusion criteria

* Contraindications to MRI scan (defibrillator, pacemaker, metallic foreign body, severe claustrophobia etc.)
* Contraindications to gadolinium
* Age above 85 years old or younger than 20 years old
* Pregnancy or breast feeding
* Any other condition which, in the opinion of the Investigator, would make the patient unsuitable for enrolment for the trial or could interfere with the completion of the study

Study design

Purpose of the study

Other

Allocation to intervention

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Single group

Other design features

Phase

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Recruiting

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

1/01/2022

Actual

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

1/03/2027

Actual

Sample size

Target

476

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW,QLD,VIC,WA

Recruitment hospital [1]

Royal Prince Alfred Hospital - Camperdown

Recruitment hospital [2]

Concord Repatriation General Hospital - Concord

Recruitment hospital [3]

Gosford Hospital - Gosford

Recruitment hospital [4]

Prince of Wales Hospital - Randwick

Recruitment hospital [5]

Westmead Hospital - Westmead

Recruitment hospital [6]

Princess Alexandra Hospital - Brisbane

Recruitment hospital [7]

St Vincent's Hospital Melbourne - Fitzroy

Recruitment hospital [8]

Austin Hospital - Heidelberg

Recruitment hospital [9]

Royal Perth Hospital - Perth

Recruitment postcode(s) [1]

2050 - Camperdown

Recruitment postcode(s) [2]

2139 - Concord

Recruitment postcode(s) [3]

- Gosford

Recruitment postcode(s) [4]

2031 - Randwick

Recruitment postcode(s) [5]

2145 - Westmead

Recruitment postcode(s) [6]

- Brisbane

Recruitment postcode(s) [7]

3065 - Fitzroy

Recruitment postcode(s) [8]

3084 - Heidelberg

Recruitment postcode(s) [9]

- Perth

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Auckland

Funding & Sponsors

Primary sponsor type

Other

Name

Concord Repatriation General Hospital

Address

Country

Ethics approval

Ethics application status

Summary

Brief summary

All international guidelines recommend 6-monthly ultrasound surveillance for patients at risk for liver cancer (hepatocellular carcinoma or HCC), such as patients with cirrhosis. The aim of surveillance is to detect HCC at an early stage when it is still potentially curable. Currently only 4 out of 10 HCCs are detected at the early stage.

Ultrasound surveillance for HCC has a wide ranging sensitivity, dependent on many factors such as operator experience, patient body habitus and liver parenchymal heterogeneity due to chronic liver disease and cirrhosis. In a select group of patients, surveillance ultrasound can be suboptimal or near non-diagnostic.

Currently no guideline offers an alternative surveillance tool for patients who have suboptimal surveillance ultrasounds.

Trial website

https://clinicaltrials.gov/study/NCT04455932

Trial related presentations / publications

Son JH, Choi SH, Kim SY, Jang HY, Byun JH, Won HJ, Lee SJ, Lim YS. Validation of US Liver Imaging Reporting and Data System Version 2017 in Patients at High Risk for Hepatocellular Carcinoma. Radiology. 2019 Aug;292(2):390-397. doi: 10.1148/radiol.2019190035. Epub 2019 Jun 18.
Singal AG, Pillai A, Tiro J. Early detection, curative treatment, and survival rates for hepatocellular carcinoma surveillance in patients with cirrhosis: a meta-analysis. PLoS Med. 2014 Apr 1;11(4):e1001624. doi: 10.1371/journal.pmed.1001624. eCollection 2014 Apr.
Tzartzeva K, Obi J, Rich NE, Parikh ND, Marrero JA, Yopp A, Waljee AK, Singal AG. Surveillance Imaging and Alpha Fetoprotein for Early Detection of Hepatocellular Carcinoma in Patients With Cirrhosis: A Meta-analysis. Gastroenterology. 2018 May;154(6):1706-1718.e1. doi: 10.1053/j.gastro.2018.01.064. Epub 2018 Feb 6.
Hanna RF, Miloushev VZ, Tang A, Finklestone LA, Brejt SZ, Sandhu RS, Santillan CS, Wolfson T, Gamst A, Sirlin CB. Comparative 13-year meta-analysis of the sensitivity and positive predictive value of ultrasound, CT, and MRI for detecting hepatocellular carcinoma. Abdom Radiol (NY). 2016 Jan;41(1):71-90. doi: 10.1007/s00261-015-0592-8.
Colli A, Fraquelli M, Casazza G, Massironi S, Colucci A, Conte D, Duca P. Accuracy of ultrasonography, spiral CT, magnetic resonance, and alpha-fetoprotein in diagnosing hepatocellular carcinoma: a systematic review. Am J Gastroenterol. 2006 Mar;101(3):513-23. doi: 10.1111/j.1572-0241.2006.00467.x.
Chernyak V, Fowler KJ, Kamaya A, Kielar AZ, Elsayes KM, Bashir MR, Kono Y, Do RK, Mitchell DG, Singal AG, Tang A, Sirlin CB. Liver Imaging Reporting and Data System (LI-RADS) Version 2018: Imaging of Hepatocellular Carcinoma in At-Risk Patients. Radiology. 2018 Dec;289(3):816-830. doi: 10.1148/radiol.2018181494. Epub 2018 Sep 25.
European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018 Jul;69(1):182-236. doi: 10.1016/j.jhep.2018.03.019. Epub 2018 Apr 5. No abstract available. Erratum In: J Hepatol. 2019 Apr;70(4):817. doi: 10.1016/j.jhep.2019.01.020.
D'Avola D, Labgaa I, Villanueva A. Natural history of nonalcoholic steatohepatitis/nonalcoholic fatty liver disease-hepatocellular carcinoma: Magnitude of the problem from a hepatology clinic perspective. Clin Liver Dis (Hoboken). 2016 Oct 27;8(4):100-104. doi: 10.1002/cld.579. eCollection 2016 Oct. No abstract available.
Saunders D, Seidel D, Allison M, Lyratzopoulos G. Systematic review: the association between obesity and hepatocellular carcinoma - epidemiological evidence. Aliment Pharmacol Ther. 2010 May;31(10):1051-63. doi: 10.1111/j.1365-2036.2010.04271.x. Epub 2010 Feb 18.
Wang C, Wang X, Gong G, Ben Q, Qiu W, Chen Y, Li G, Wang L. Increased risk of hepatocellular carcinoma in patients with diabetes mellitus: a systematic review and meta-analysis of cohort studies. Int J Cancer. 2012 Apr 1;130(7):1639-48. doi: 10.1002/ijc.26165. Epub 2011 Jul 28.
Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016 Jul;64(1):73-84. doi: 10.1002/hep.28431. Epub 2016 Feb 22.
Chitturi S, Wong VW, Chan WK, Wong GL, Wong SK, Sollano J, Ni YH, Liu CJ, Lin YC, Lesmana LA, Kim SU, Hashimoto E, Hamaguchi M, Goh KL, Fan J, Duseja A, Dan YY, Chawla Y, Farrell G, Chan HL. The Asia-Pacific Working Party on Non-alcoholic Fatty Liver Disease guidelines 2017-Part 2: Management and special groups. J Gastroenterol Hepatol. 2018 Jan;33(1):86-98. doi: 10.1111/jgh.13856. No abstract available.
Benson AB 3rd, D'Angelica MI, Abbott DE, Abrams TA, Alberts SR, Saenz DA, Are C, Brown DB, Chang DT, Covey AM, Hawkins W, Iyer R, Jacob R, Karachristos A, Kelley RK, Kim R, Palta M, Park JO, Sahai V, Schefter T, Schmidt C, Sicklick JK, Singh G, Sohal D, Stein S, Tian GG, Vauthey JN, Venook AP, Zhu AX, Hoffmann KG, Darlow S. NCCN Guidelines Insights: Hepatobiliary Cancers, Version 1.2017. J Natl Compr Canc Netw. 2017 May;15(5):563-573. doi: 10.6004/jnccn.2017.0059.
Burak KW, Sherman M. Hepatocellular carcinoma: Consensus, controversies and future directions. A report from the Canadian Association for the Study of the Liver Hepatocellular Carcinoma Meeting. Can J Gastroenterol Hepatol. 2015 May;29(4):178-84. doi: 10.1155/2015/824263.
Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, Zhu AX, Murad MH, Marrero JA. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018 Jan;67(1):358-380. doi: 10.1002/hep.29086. No abstract available.
Kokudo N, Hasegawa K, Akahane M, Igaki H, Izumi N, Ichida T, Uemoto S, Kaneko S, Kawasaki S, Ku Y, Kudo M, Kubo S, Takayama T, Tateishi R, Fukuda T, Matsui O, Matsuyama Y, Murakami T, Arii S, Okazaki M, Makuuchi M. Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma: The Japan Society of Hepatology 2013 update (3rd JSH-HCC Guidelines). Hepatol Res. 2015 Jan;45(2). doi: 10.1111/hepr.12464.
Marrero JA, Ahn J, Rajender Reddy K; Americal College of Gastroenterology. ACG clinical guideline: the diagnosis and management of focal liver lesions. Am J Gastroenterol. 2014 Sep;109(9):1328-47; quiz 1348. doi: 10.1038/ajg.2014.213. Epub 2014 Aug 19.
Korean Liver Cancer Study Group (KLCSG); National Cancer Center, Korea (NCC). 2014 KLCSG-NCC Korea Practice Guideline for the Management of Hepatocellular Carcinoma. Gut Liver. 2015 May 23;9(3):267-317. doi: 10.5009/gnl14460.
Besa C, Lewis S, Pandharipande PV, Chhatwal J, Kamath A, Cooper N, Knight-Greenfield A, Babb JS, Boffetta P, Padron N, Sirlin CB, Taouli B. Hepatocellular carcinoma detection: diagnostic performance of a simulated abbreviated MRI protocol combining diffusion-weighted and T1-weighted imaging at the delayed phase post gadoxetic acid. Abdom Radiol (NY). 2017 Jan;42(1):179-190. doi: 10.1007/s00261-016-0841-5. Erratum In: Abdom Radiol (NY). 2018 Mar;43(3):760. doi: 10.1007/s00261-017-1256-7.
Tillman BG, Gorman JD, Hru JM, Lee MH, King MC, Sirlin CB, Marks RM. Diagnostic per-lesion performance of a simulated gadoxetate disodium-enhanced abbreviated MRI protocol for hepatocellular carcinoma screening. Clin Radiol. 2018 May;73(5):485-493. doi: 10.1016/j.crad.2017.11.013. Epub 2017 Dec 12.
Lee JY, Huo EJ, Weinstein S, Santos C, Monto A, Corvera CU, Yee J, Hope TA. Evaluation of an abbreviated screening MRI protocol for patients at risk for hepatocellular carcinoma. Abdom Radiol (NY). 2018 Jul;43(7):1627-1633. doi: 10.1007/s00261-017-1339-5.
Chan MV, McDonald SJ, Ong YY, Mastrocostas K, Ho E, Huo YR, Santhakumar C, Lee AU, Yang J. HCC screening: assessment of an abbreviated non-contrast MRI protocol. Eur Radiol Exp. 2019 Dec 18;3(1):49. doi: 10.1186/s41747-019-0126-1.
Park SH, Kim B, Kim SY, Shim YS, Kim JH, Huh J, Kim HJ, Kim KW, Lee SS. Abbreviated MRI with optional multiphasic CT as an alternative to full-sequence MRI: LI-RADS validation in a HCC-screening cohort. Eur Radiol. 2020 Apr;30(4):2302-2311. doi: 10.1007/s00330-019-06546-5. Epub 2019 Dec 19.
Lewis S, Kamath A, Chatterji M, Patel A, Shyknevsky I, Dyvorne HA, Kuehn B, Taouli B. Diffusion-weighted imaging of the liver in patients with chronic liver disease: comparison of monopolar and bipolar diffusion gradients for image quality and lesion detection. AJR Am J Roentgenol. 2015 Jan;204(1):59-68. doi: 10.2214/AJR.13.11695.
Whang S, Choi MH, Choi JI, Youn SY, Kim DH, Rha SE. Comparison of diagnostic performance of non-contrast MRI and abbreviated MRI using gadoxetic acid in initially diagnosed hepatocellular carcinoma patients: a simulation study of surveillance for hepatocellular carcinomas. Eur Radiol. 2020 Aug;30(8):4150-4163. doi: 10.1007/s00330-020-06754-4. Epub 2020 Mar 12.
Marrero JA, Kulik LM, Sirlin CB, Zhu AX, Finn RS, Abecassis MM, Roberts LR, Heimbach JK. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018 Aug;68(2):723-750. doi: 10.1002/hep.29913. No abstract available.

Public notes

Contacts

Principal investigator

Name

Jessica Yang, MBBS

Address

Concord Repatriation General Hospital

Country

Phone

Fax

Contact person for public queries

Name

Jessica Yang, MBBS

Address

Country

Phone

+61297676495

Fax

[email protected]

Contact person for scientific queries

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Type	Citations or Other Details
Journal	Son JH, Choi SH, Kim SY, Jang HY, Byun JH, Won HJ,... [More Details]
Journal	Singal AG, Pillai A, Tiro J. Early detection, cura... [More Details]
Journal	Tzartzeva K, Obi J, Rich NE, Parikh ND, Marrero JA... [More Details]
Journal	Hanna RF, Miloushev VZ, Tang A, Finklestone LA, Br... [More Details]
Journal	Colli A, Fraquelli M, Casazza G, Massironi S, Colu... [More Details]
Journal	Chernyak V, Fowler KJ, Kamaya A, Kielar AZ, Elsaye... [More Details]
Journal	European Association for the Study of the Liver. E... [More Details]
Journal	D'Avola D, Labgaa I, Villanueva A. Natural history... [More Details]
Journal	Saunders D, Seidel D, Allison M, Lyratzopoulos G. ... [More Details]
Journal	Wang C, Wang X, Gong G, Ben Q, Qiu W, Chen Y, Li G... [More Details]
Journal	Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henr... [More Details]
Journal	Chitturi S, Wong VW, Chan WK, Wong GL, Wong SK, So... [More Details]
Journal	Benson AB 3rd, D'Angelica MI, Abbott DE, Abrams TA... [More Details]
Journal	Burak KW, Sherman M. Hepatocellular carcinoma: Con... [More Details]
Journal	Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecass... [More Details]
Journal	Kokudo N, Hasegawa K, Akahane M, Igaki H, Izumi N,... [More Details]
Journal	Marrero JA, Ahn J, Rajender Reddy K; Americal Coll... [More Details]
Journal	Korean Liver Cancer Study Group (KLCSG); National ... [More Details]
Journal	Besa C, Lewis S, Pandharipande PV, Chhatwal J, Kam... [More Details]
Journal	Tillman BG, Gorman JD, Hru JM, Lee MH, King MC, Si... [More Details]
Journal	Lee JY, Huo EJ, Weinstein S, Santos C, Monto A, Co... [More Details]
Journal	Chan MV, McDonald SJ, Ong YY, Mastrocostas K, Ho E... [More Details]
Journal	Park SH, Kim B, Kim SY, Shim YS, Kim JH, Huh J, Ki... [More Details]
Journal	Lewis S, Kamath A, Chatterji M, Patel A, Shyknevsk... [More Details]
Journal	Whang S, Choi MH, Choi JI, Youn SY, Kim DH, Rha SE... [More Details]
Journal	Marrero JA, Kulik LM, Sirlin CB, Zhu AX, Finn RS, ... [More Details]

Results not provided in https://clinicaltrials.gov/study/NCT04455932

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For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04455932