Hepatocellular CarcinomaNCT03047603
Evaluation of Diagnostic Efficiency of PIVKA-II and Other Tumor Markers in HCC
An observational study of Hepatocellular Carcinoma, run by Eastern Hepatobiliary Surgery Hospital at 1 site in China.
Trial summary
The incidence of Hepatocellular carcinoma (HCC) is increasing worldwide. However, most of HCC cases were at advanced stage when the diagnosis established.Early diagnosis improves the prognosis.The study is intended to evaluate the diagnostic efficiency of Protein Induced by Vitamin K Absence or… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- PIVKA-II
- How many people
- 4,005 participants
- Where
- 1 siteChina
- Study dates
- 1 May 2016to 20 Mar 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
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 18 to 85 years
- All sexes
- Adult, Older adult
Study population: The participants will be recruited through outpatient clinics.
Who may be able to join
- Age between 18 and 85
- Receiving no treatment before diagnosis
- Establishing Diagnosis according to the Asian Pacific Association for the Study of Liver(APASL) criteria
Who cannot join
- Clinical data missing
- Laboratory tests information missing
- Serum samples doesn't qualified
- Obstructive jaundice patients
- Medical history of taking warfarin
Trial locations and contacts
1 site in 1 country.
China1 site
Eastern hepatobiliary surgery hospital
Shanghai, Shanghai Municipality, 200438
About this study
Official title: Evaluation of Diagnostic and Differential Diagnostic Significance of a Combination of PIVKA-II and Other Tumor Markers in Hepatocellular Carcinoma
The incidence of Hepatocellular carcinoma (HCC) is increasing worldwide. However, most of HCC cases were at advanced stage when the diagnosis established.Early diagnosis improves the prognosis.The study is intended to evaluate the diagnostic efficiency of Protein Induced by Vitamin K Absence or antagonist-II(PIVKA-II). This study is a international multicenter study joined by several hospitals in China,Singapore,Thailand and Vietnam. Participants including healthy control,HCC,metastatic liver cancer,Hepatitis B virus(HBV) and liver cirrhosis are consecutively recruited into the cohort. All the serum samples are collected before any treatments and will be tested in single center in order to decrease bias. Serum samples were tested for PIVKA-II,alpha-fetoprotein and biochemical indexes including alanine aminotransferase(ALT),aspartate aminotransferase(AST),gamma-glutamyl transferase(GGT),alpha-l-fucosidase(AFU),etc.
Read the detailed description
Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide.Early diagnosis improves the prognosis. Protein induced by vitamin K antagonist-II (PIVKA-II), also known as des-γ-carboxyprothrombin (DCP) or acarboxy prothrombin, is an abnormal form of prothrombin induced by vitamin K absence or antagonist-II. The study is intended to evaluate the diagnostic efficiency of Protein Induced by Vitamin K Absence or antagonist-II(PIVKA-II). PIVKA-II as an effective tumor marker for hepatocellular carcinoma(HCC) has been widely used in the western countries where most cases are hepatitis C virus(HCV) related.However, the majority of HCCs in China are HBV related. Despite the extensive application of PIVKA-II in some hospitals from China, the diagnostic efficiency including sensitivity,specificity,positive predictive value and negative predictive value still needs more clinical data to evaluate. The research purposes list as follows：1.Determination of diagnostic Cut-off value 2.Evaluation of diagnostic efficiency of PIVKA-II 3.Evaluation of the combination of PIVKA-II and other tumor markers for HCC. This study is an international multicenter study joined by several hospitals in China,Singapore,Thailand and Vietnam. Participants including healthy control,HCC,metastatic liver cancer,HBV and liver cirrhosis are consecutively recruited into the cohort. All the serum samples are collected before any treatments and will be tested in single center in order to decrease bias. Serum samples were tested for PIVKA-II,Alpha-fetoprotein(AFP)，alpha-fetoprotein L3 and biochemical indexes including ALT,AST,GGT,AFU,etc. The diagnosis of HCC was based on histopathology. All HCC diagnoses were confirmed at the time of analysis.The Student's t-test (or Mann-Whitney test) was used to compare continuous variables, and the chi-square test (or Fisher's exact test) was used for categorical variables. A receiver operator characteristic (ROC) curve was used to assess the performance characteristic of PIVKA-II,AFP,AFP-L3 measurement.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- PIVKA-II
- Keywords
- Hepatocellular carcinoma, Protein induced by vitamin K absence or antagonist-II, Differential diagnosis, Des-γ-carboxy prothrombin, Alpha-fetoprotein, Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein-fetoprotein
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PIVKA-IIDiagnostic test
Also called DCP
Serum samples are tested for tumor markers including PIVKA-II,AFP,AFP-L3% and biochemical tests.
| Study group | Role | What they receive |
|---|---|---|
| Healthy control | The healthy control group consist of people undergoing routine medical examination. Serum samples are collected. Receives: Diagnostic Test: PIVKA-II | |
| Metastatic liver cancer patients | Serum samples are collected. Receives: Diagnostic Test: PIVKA-II | |
| Hepatocellular carcinoma patients | Serum samples are collected before liver resection. Receives: Diagnostic Test: PIVKA-II | |
| Chronic liver disease patients | This group is comprised of liver cirrhosis and chronic hepatitis B patients. The diagnosis of liver cirrhosis are based on triple-phase contrast enhanced computed tomography, magnetic resonance imaging. Receives: Diagnostic Test: PIVKA-II |
What is being measured
The primary outcome is the main question the study is designed to answer.
PIVKA-II
Using PIVKA-II assay kit(chemiluminescent microparticle immunoassay).
Measured: Day one
Secondary outcomes (2)
AFP,AFP-L3%
Measured: Day one
ALT, AST，γ-GT， AFU
Measured: Day one
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2017 (estimated)
- Study start1 May 2016
- Primary completion1 Sep 2018
- Study completion20 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- 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
- 4,005 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eastern Hepatobiliary Surgery Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Abbott Diagnostics Division, Peking University First Hospital, The First Hospital of Jilin University, RenJi Hospital, First Affiliated Hospital Xi'an Jiaotong University, Gansu Provincial Hospital, Henan Provincial People's Hospital, Sun Yat-sen University, Sichuan Provincial People's Hospital
- Responsible party
- Principal investigator, Tian Yang, Eastern Hepatobiliary Surgery Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03047603
- Sponsor's protocol ID
- Pivkaii
- Status last verified
- Feb 2024
- First submitted
- 6 Feb 2017
- Last updated
- 20 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Yang T, Xing H, Wang G, Wang N, Liu M, Yan C, Li H, Wei L, Li S, Fan Z, Shi M, Chen W, Cai S, Pawlik TM, Soh A, Beshiri A, Lau WY, Wu M, Zheng Y, Shen F. A Novel Online Calculator Based on Serum Biomarkers to Detect Hepatocellular Carcinoma among Patients with Hepatitis B. Clin Chem. 2019 Dec;65(12):1543-1553. doi: 10.1373/clinchem.2019.308965. Epub 2019 Oct 31.
PubMed 31672853Yan C, Hu J, Yang J, Chen Z, Li H, Wei L, Zhang W, Xing H, Sang G, Wang X, Han R, Liu P, Li Z, Li Z, Huang Y, Jiang L, Li S, Dai S, Wang N, Yang Y, Ma L, Soh A, Beshiri A, Shen F, Yang T, Fan Z, Zheng Y, Chen W. Serum ARCHITECT PIVKA-II reference interval in healthy Chinese adults: Sub-analysis from a prospective multicenter study. Clin Biochem. 2018 Apr;54:32-36. doi: 10.1016/j.clinbiochem.2018.02.007. Epub 2018 Feb 12.
PubMed 29448045Yan C, Yang J, Wei L, Hu J, Song J, Wang X, Han R, Huang Y, Zhang W, Soh A, Beshiri A, Fan Z, Zheng Y, Chen W. Serum reference interval of ARCHITECT alpha-fetoprotein in healthy Chinese Han adults: Sub-analysis of a prospective multi-center study. Clin Biochem. 2018 Feb;52:164-166. doi: 10.1016/j.clinbiochem.2017.11.002. Epub 2017 Nov 10.
PubMed 29129627
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Diagnostic and Differential Diagnostic Significance of a Combination of PIVKA-II and Other Tumor Markers in Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT03047603
- Acronym / sponsor ID
- Pivkaii
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Hepatocellular carcinoma, Protein induced by vitamin K absence or antagonist-II, Differential diagnosis, Des-γ-carboxy prothrombin, Alpha-fetoprotein, Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein-fetoprotein
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 4,005 participants (actual)
- Lead sponsor
- Eastern Hepatobiliary Surgery HospitalUniversity, hospital or other
- Collaborators
- Abbott Diagnostics Division, Peking University First Hospital, The First Hospital of Jilin University, RenJi Hospital, First Affiliated Hospital Xi'an Jiaotong University, Gansu Provincial Hospital, Henan Provincial People's Hospital, Sun Yat-sen University, Sichuan Provincial People's Hospital
- Study start
- 1 May 2016 (actual)
- Primary completion
- 1 Sep 2018 (actual)
- Study completion
- 20 Mar 2019 (actual)
- First posted
- 9 Feb 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The incidence of Hepatocellular carcinoma (HCC) is increasing worldwide. However, most of HCC cases were at advanced stage when the diagnosis established.Early diagnosis improves the prognosis.The study is intended to evaluate the diagnostic efficiency of Protein Induced by Vitamin K Absence or antagonist-II(PIVKA-II). This study is a international multicenter study joined by several hospitals in China,Singapore,Thailand and Vietnam. Participants including healthy control,HCC,metastatic liver cancer,Hepatitis B virus(HBV) and liver cirrhosis are consecutively recruited into the cohort. All the serum samples are collected before any treatments and will be tested in single center in order to decrease bias. Serum samples were tested for PIVKA-II,alpha-fetoprotein and biochemical indexes including alanine aminotransferase(ALT),aspartate aminotransferase(AST),gamma-glutamyl transferase(GGT),alpha-l-fucosidase(AFU),etc.
Detailed description
Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide.Early diagnosis improves the prognosis. Protein induced by vitamin K antagonist-II (PIVKA-II), also known as des-γ-carboxyprothrombin (DCP) or acarboxy prothrombin, is an abnormal form of prothrombin induced by vitamin K absence or antagonist-II. The study is intended to evaluate the diagnostic efficiency of Protein Induced by Vitamin K Absence or antagonist-II(PIVKA-II). PIVKA-II as an effective tumor marker for hepatocellular carcinoma(HCC) has been widely used in the western countries where most cases are hepatitis C virus(HCV) related.However, the majority of HCCs in China are HBV related. Despite the extensive application of PIVKA-II in some hospitals from China, the diagnostic efficiency including sensitivity,specificity,positive predictive value and negative predictive value still needs more clinical data to evaluate. The research purposes list as follows：1.Determination of diagnostic Cut-off value 2.Evaluation of diagnostic efficiency of PIVKA-II 3.Evaluation of the combination of PIVKA-II and other tumor markers for HCC. This study is an international multicenter study joined by several hospitals in China,Singapore,Thailand and Vietnam. Participants including healthy control,HCC,metastatic liver cancer,HBV and liver cirrhosis are consecutively recruited into the cohort. All the serum samples are collected before any treatments and will be tested in single center in order to decrease bias. Serum samples were tested for PIVKA-II,Alpha-fetoprotein(AFP)，alpha-fetoprotein L3 and biochemical indexes including ALT,AST,GGT,AFU,etc. The diagnosis of HCC was based on histopathology. All HCC diagnoses were confirmed at the time of analysis.The Student's t-test (or Mann-Whitney test) was used to compare continuous variables, and the chi-square test (or Fisher's exact test) was used for categorical variables. A receiver operator characteristic (ROC) curve was used to assess the performance characteristic of PIVKA-II,AFP,AFP-L3 measurement.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Healthy control | – | Diagnostic Test: PIVKA-IIThe healthy control group consist of people undergoing routine medical examination. Serum samples are collected. |
| Metastatic liver cancer patients | – | Diagnostic Test: PIVKA-IISerum samples are collected. |
| Hepatocellular carcinoma patients | – | Diagnostic Test: PIVKA-IISerum samples are collected before liver resection. |
| Chronic liver disease patients | – | Diagnostic Test: PIVKA-IIThis group is comprised of liver cirrhosis and chronic hepatitis B patients. The diagnosis of liver cirrhosis are based on triple-phase contrast enhanced computed tomography, magnetic resonance imaging. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- The participants will be recruited through outpatient clinics.
Key inclusion criteria (3 listed)
- Age between 18 and 85
- Receiving no treatment before diagnosis
- Establishing Diagnosis according to the Asian Pacific Association for the Study of Liver(APASL) criteria
Key exclusion criteria (5 listed)
- Clinical data missing
- Laboratory tests information missing
- Serum samples doesn't qualified
- Obstructive jaundice patients
- Medical history of taking warfarin
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PIVKA-IIAlso: DCPSerum samples are tested for tumor markers including PIVKA-II,AFP,AFP-L3% and biochemical tests. | Diagnostic test | Chronic liver disease patients, Healthy control, Hepatocellular carcinoma patients, Metastatic liver cancer patients |
Primary outcome
PIVKA-II
Time frame: Day one
Using PIVKA-II assay kit(chemiluminescent microparticle immunoassay).
2 secondary outcomes
AFP,AFP-L3%
Time frame: Day one
ALT, AST，γ-GT， AFU
Time frame: Day one
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2024.
- Derived from this study: PubMed 31672853Yang T, Xing H, Wang G, Wang N, Liu M, Yan C, Li H, Wei L, Li S, Fan Z, Shi M, Chen W, Cai S, Pawlik TM, Soh A, Beshiri A, Lau WY, Wu M, Zheng Y, Shen F. A Novel Online Calculator Based on Serum Biomarkers to Detect Hepatocellular Carcinoma among Patients with Hepatitis B. Clin Chem. 2019 Dec;65(12):1543-1553. doi: 10.1373/clinchem.2019.308965. Epub 2019 Oct 31.
- Derived from this study: PubMed 29448045Yan C, Hu J, Yang J, Chen Z, Li H, Wei L, Zhang W, Xing H, Sang G, Wang X, Han R, Liu P, Li Z, Li Z, Huang Y, Jiang L, Li S, Dai S, Wang N, Yang Y, Ma L, Soh A, Beshiri A, Shen F, Yang T, Fan Z, Zheng Y, Chen W. Serum ARCHITECT PIVKA-II reference interval in healthy Chinese adults: Sub-analysis from a prospective multicenter study. Clin Biochem. 2018 Apr;54:32-36. doi: 10.1016/j.clinbiochem.2018.02.007. Epub 2018 Feb 12.
- Derived from this study: PubMed 29129627Yan C, Yang J, Wei L, Hu J, Song J, Wang X, Han R, Huang Y, Zhang W, Soh A, Beshiri A, Fan Z, Zheng Y, Chen W. Serum reference interval of ARCHITECT alpha-fetoprotein in healthy Chinese Han adults: Sub-analysis of a prospective multi-center study. Clin Biochem. 2018 Feb;52:164-166. doi: 10.1016/j.clinbiochem.2017.11.002. Epub 2017 Nov 10.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Hepatocellular Carcinoma, run by Eastern Hepatobiliary Surgery Hospital at 1 site in China.
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 3 inclusion and 5 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 20 Feb 2024. 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 China. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
PIVKA-II (time frame: Day one). 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 NCT03047603, 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 20 Feb 2024; AzTrials last refreshed its copy on 8 Nov 2026.