NCT04414956

Brief Summary

In this study, three biomarkers tests (AFP, AFP-L3 and PIVKA-II) and abdominal sonography or CT scans are performed every 6 months to detect hepatocellular carcinoma (HCC) early in patients with cirrhosis, a high-risk group of HCC. The aim of this study is to confirm the early HCC diagnosis rate in patients with cirrhosis and compare the detection efficacy between tests.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
1,418

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Jul 2016

Longer than P75 for not_applicable

Geographic Reach
1 country

15 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2016

Completed
3.9 years until next milestone

First Submitted

Initial submission to the registry

May 20, 2020

Completed
15 days until next milestone

First Posted

Study publicly available on registry

June 4, 2020

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2023

Completed
2.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 28, 2026

Completed
Last Updated

June 4, 2020

Status Verified

May 1, 2020

Enrollment Period

7 years

First QC Date

May 20, 2020

Last Update Submit

May 30, 2020

Conditions

Liver CirrhosisHepatocellular CarcinomaSurveillance

Keywords

Liver CirrhosisHepatocellular CarcinomaSurveillanceAFP-L3AFPPIVKA-IISonographyCT

Outcome Measures

Primary Outcomes (1)

  • HCC occurrence

    Detection of HCC occurrence by three biomarkers and two image modalities

    3 years after enrollment

Secondary Outcomes (1)

  • Early HCC occurrence

    3 years after enrollment

Study Arms (1)

Surveillance

OTHER

All participants will be examined with three biomarker tests and sonography every six months and contrast-enhanced CT annually.

Diagnostic Test: AFP-L3Diagnostic Test: AFPDiagnostic Test: PIVKA-IIDiagnostic Test: SonographyDiagnostic Test: CT

Interventions

AFP-L3DIAGNOSTIC_TEST

AFP-L3 will be tested using serum sample every 6 months.

Also known as: Lens culinaris agglutinin-reactive fraction of AFP
Surveillance
AFPDIAGNOSTIC_TEST

AFP will be tested using serum sample every 6 months.

Also known as: Alpha fetoprotein
Surveillance
PIVKA-IIDIAGNOSTIC_TEST

PIVKA-II will be tested using serum sample every 6 months.

Also known as: Protein induced by vitamin K absence or antagonist-II, des-gamma-carboxy prothrombin
Surveillance
SonographyDIAGNOSTIC_TEST

Sonography will be tested by experts every 6 months.

Also known as: Ultrasound, US
Surveillance
CTDIAGNOSTIC_TEST

Contrast-enhanced CT will be tested annually.

Also known as: Computed tomography
Surveillance

Eligibility Criteria

Age19 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with liver cirrhosis meeting one of the followings:
  • i. Histologically confirmed liver cirrhosis ii. Imaging findings with liver cirrhosis (liver surface undulation, irregularity, or nodularity by US, CT, or MRI) plus one of followings: liver stiffness measurement ≥ 12.5 kilopascal, esophago-gastric varices, thrombocytopenia (\<120,000/mm3), hypoalbuminemia (\<3.5 g/dL), splenomegaly ≥12 cm) iii. Imaging findings with liver cirrhosis together with biomarkers suggesting liver cirrhosis (APRI ≥2.0 or fibrosis-4 ≥3.6) iv. Imaging findings with liver cirrhosis with history of hepatic decompensation (ascites, esophago-gastric variceal bleeding, jaundice, hepatic encephalopathy))
  • Expected survival more than 1 year
  • Child Pugh score 5-10 at the time of enrollment
  • Serum creatinine ≤1.5mg/dL
  • Age between 19 and 75 years old
  • No significant underlying medical illness affecting patient's survival
  • Patients available for regular follow-up according to the study protocol

You may not qualify if:

  • History of HCC
  • AFP \>20 ng/mL
  • Hepatic nodule less than 1 cm on US but imaging findings suggesting HCC by contrast enhanced US, CT, or MRI
  • Child-Pugh score ≥ 11
  • History of liver transplantation
  • Expecting liver transplantation within 1 year
  • Hypersensitivity on CT contrast dye
  • Any contraindication for CT
  • Not able to perform abdominal US
  • Other uncontrolled malignancy
  • Patients taking warfarin

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

Korea University Ansan Hospital

Ansan, Gyeonggi-do, 15355, South Korea

RECRUITING

The Catholic University of Korea Uijeongbu St.Mary's Hospital

Uijeongbu-si, Gyeonggi-do, 11765, South Korea

RECRUITING

Keimyung University Dongsan Medical Center

Daegu, 42601, South Korea

RECRUITING

Inje University SangGye Paik Hospital

Seoul, 01757, South Korea

RECRUITING

Korea University Anam Hospital

Seoul, 02841, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Severance Hospital

Seoul, 03722, South Korea

RECRUITING

Soonchunhyang University Seoul Hospital

Seoul, 04401, South Korea

RECRUITING

Hanyang University Hospital

Seoul, 04763, South Korea

RECRUITING

Konkuk University Hospital

Seoul, 05030, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

The Catholic University of Korea Seoul St.Mary's Hospital

Seoul, 06591, South Korea

RECRUITING

Chung-Ang University Hosptial

Seoul, 06973, South Korea

RECRUITING

Korea University Guro Hospital

Seoul, 08308, South Korea

RECRUITING

Related Publications (17)

  • El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011 Sep 22;365(12):1118-27. doi: 10.1056/NEJMra1001683. No abstract available.

    PMID: 21992124BACKGROUND

  • 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.

    PMID: 25918260BACKGROUND

  • Yim HJ, Suh SJ, Um SH. Current management of hepatocellular carcinoma: an Eastern perspective. World J Gastroenterol. 2015 Apr 7;21(13):3826-42. doi: 10.3748/wjg.v21.i13.3826.

    PMID: 25852267BACKGROUND

  • European Association For The Study Of The Liver; European Organisation For Research And Treatment Of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012 Apr;56(4):908-43. doi: 10.1016/j.jhep.2011.12.001. No abstract available.

    PMID: 22424438BACKGROUND

  • Yim SY, Seo YS, Jung CH, Kim TH, Lee JM, Kim ES, Keum B, Jong YK, An H, Kim JH, Yim HJ, Kim DS, Jeen YT, Yeon JE, Lee HS, Chun HJ, Byun KS, Um SH, Kim CD, Ryu HS. The management and prognosis of patients with hepatocellular carcinoma: what has changed in 20 years? Liver Int. 2016 Mar;36(3):445-53. doi: 10.1111/liv.12960. Epub 2015 Oct 12.

    PMID: 26352789RESULT

  • Sterling RK, Jeffers L, Gordon F, Venook AP, Reddy KR, Satomura S, Kanke F, Schwartz ME, Sherman M. Utility of Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein and des-gamma-carboxy prothrombin, alone or in combination, as biomarkers for hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2009 Jan;7(1):104-13. doi: 10.1016/j.cgh.2008.08.041. Epub 2008 Sep 17.

    PMID: 18849011RESULT

  • Taketa K, Sekiya C, Namiki M, Akamatsu K, Ohta Y, Endo Y, Kosaka K. Lectin-reactive profiles of alpha-fetoprotein characterizing hepatocellular carcinoma and related conditions. Gastroenterology. 1990 Aug;99(2):508-18. doi: 10.1016/0016-5085(90)91034-4.

    PMID: 1694805RESULT

  • Taketa K, Endo Y, Sekiya C, Tanikawa K, Koji T, Taga H, Satomura S, Matsuura S, Kawai T, Hirai H. A collaborative study for the evaluation of lectin-reactive alpha-fetoproteins in early detection of hepatocellular carcinoma. Cancer Res. 1993 Nov 15;53(22):5419-23.

    PMID: 7693340RESULT

  • Oka H, Saito A, Ito K, Kumada T, Satomura S, Kasugai H, Osaki Y, Seki T, Kudo M, Tanaka M; Collaborative Hepato-Oncology Study Group of Japan. Multicenter prospective analysis of newly diagnosed hepatocellular carcinoma with respect to the percentage of Lens culinaris agglutinin-reactive alpha-fetoprotein. J Gastroenterol Hepatol. 2001 Dec;16(12):1378-83. doi: 10.1046/j.1440-1746.2001.02643.x.

    PMID: 11851836RESULT

  • Nakamura S, Nouso K, Sakaguchi K, Ito YM, Ohashi Y, Kobayashi Y, Toshikuni N, Tanaka H, Miyake Y, Matsumoto E, Shiratori Y. Sensitivity and specificity of des-gamma-carboxy prothrombin for diagnosis of patients with hepatocellular carcinomas varies according to tumor size. Am J Gastroenterol. 2006 Sep;101(9):2038-43. doi: 10.1111/j.1572-0241.2006.00681.x. Epub 2006 Jul 18.

    PMID: 16848811RESULT

  • Choi JY, Jung SW, Kim HY, Kim M, Kim Y, Kim DG, Oh EJ. Diagnostic value of AFP-L3 and PIVKA-II in hepatocellular carcinoma according to total-AFP. World J Gastroenterol. 2013 Jan 21;19(3):339-46. doi: 10.3748/wjg.v19.i3.339.

    PMID: 23372355RESULT

  • Yoon YJ, Han KH, Kim DY. Role of serum prothrombin induced by vitamin K absence or antagonist-II in the early detection of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. Scand J Gastroenterol. 2009;44(7):861-6. doi: 10.1080/00365520902903034.

    PMID: 19391065RESULT

  • Seo SI, Kim HS, Kim WJ, Shin WG, Kim DJ, Kim KH, Jang MK, Lee JH, Kim JS, Kim HY, Kim DJ, Lee MS, Park CK. Diagnostic value of PIVKA-II and alpha-fetoprotein in hepatitis B virus-associated hepatocellular carcinoma. World J Gastroenterol. 2015 Apr 7;21(13):3928-35. doi: 10.3748/wjg.v21.i13.3928.

    PMID: 25852278RESULT

  • Lim TS, Kim DY, Han KH, Kim HS, Shin SH, Jung KS, Kim BK, Kim SU, Park JY, Ahn SH. Combined use of AFP, PIVKA-II, and AFP-L3 as tumor markers enhances diagnostic accuracy for hepatocellular carcinoma in cirrhotic patients. Scand J Gastroenterol. 2016 Mar;51(3):344-53. doi: 10.3109/00365521.2015.1082190. Epub 2015 Sep 4.

    PMID: 26340708RESULT

  • Di Martino M, De Filippis G, De Santis A, Geiger D, Del Monte M, Lombardo CV, Rossi M, Corradini SG, Mennini G, Catalano C. Hepatocellular carcinoma in cirrhotic patients: prospective comparison of US, CT and MR imaging. Eur Radiol. 2013 Apr;23(4):887-96. doi: 10.1007/s00330-012-2691-z. Epub 2012 Nov 18.

    PMID: 23179521RESULT

  • Kudo M, Matsui O, Izumi N, Iijima H, Kadoya M, Imai Y, Okusaka T, Miyayama S, Tsuchiya K, Ueshima K, Hiraoka A, Ikeda M, Ogasawara S, Yamashita T, Minami T, Yamakado K; Liver Cancer Study Group of Japan. JSH Consensus-Based Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma: 2014 Update by the Liver Cancer Study Group of Japan. Liver Cancer. 2014 Oct;3(3-4):458-68. doi: 10.1159/000343875.

    PMID: 26280007RESULT

  • Chou R, Cuevas C, Fu R, Devine B, Wasson N, Ginsburg A, Zakher B, Pappas M, Graham E, Sullivan SD. Imaging Techniques for the Diagnosis of Hepatocellular Carcinoma: A Systematic Review and Meta-analysis. Ann Intern Med. 2015 May 19;162(10):697-711. doi: 10.7326/M14-2509.

    PMID: 25984845RESULT

MeSH Terms

Conditions

Liver CirrhosisCarcinoma, Hepatocellular

Interventions

UltrasonographyTomography, X-Ray Computed

Condition Hierarchy (Ancestors)

Liver DiseasesDigestive System DiseasesFibrosisPathologic ProcessesPathological Conditions, Signs and SymptomsAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsLiver NeoplasmsDigestive System NeoplasmsNeoplasms by Site

Intervention Hierarchy (Ancestors)

Diagnostic ImagingDiagnostic Techniques and ProceduresDiagnosisImage Interpretation, Computer-AssistedRadiographic Image EnhancementImage EnhancementPhotographyRadiographyTomography, X-RayTomography

Central Study Contacts

Hyung Joon Yim, MD,PhD

CONTACT

+82-31-412-6565gudwns21@korea.ac.kr

Soon Ho Um, MD,PhD

CONTACT

+82-2-920-5019umsh@korea.ac.kr

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
SCREENING
Intervention Model
SINGLE GROUP
Model Details: Patients with cirrhosis will receive the surveillance test using three biomarker tests and sonography every six months and contrast-enhanced CT annually
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

May 20, 2020

First Posted

June 4, 2020

Study Start

July 1, 2016

Primary Completion

June 30, 2023

Study Completion

February 28, 2026

Last Updated

June 4, 2020

Record last verified: 2020-05

Data Sharing

IPD Sharing
Will not share

Locations

KR(15)