CirrhosisNCT02272504
A Protocol of the Canadian Prospective Study for Hepatocellular Carcinoma Surveillance Using Biomarkers
An observational study of Cirrhosis and Chronic Liver Diseases, run by Wako Life Sciences at 2 sites in Canada.
Trial summary
The objective of this study is to evaluate the clinical effectiveness of biomarkers, alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP), for surveillance program patients whose hepatocellular carcinoma (HCC) development may be potentially… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cirrhosis, Chronic Liver Diseases
- How many people
- 2,500 participants
- Where
- 2 sitesCanada
- Study dates
- Aug 2014to Feb 2021
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients who are at risk for the development of HCC as identified by the prior presence of chronic liver disease and cirrhosis.
Who may be able to join
- Patient who is able and willing to comply with study procedures, and signed and dated informed consent is obtained.
- Patients with a clinical suspicion of cirrhosis based on the investigator's evaluation with cirrhosis confirmed by one of the following: (see below for definition of cirrhosis). Etiology of cirrhosis will not be considered in determining inclusion in the study.
- Patients aged 18 years and older.
- Hep B Risk Score > 8 (table 1)
- Table 1 Variable Risk Score Variable Risk Score Male 2 ALT <15 0 Female 0 ALT 15-44 1 Age 30-34 0 ALT > 45 2 Age 35-39 1 HBeAg+ve 0 Age 40-44 2 Anti-HBe-positive 2 Age 45-49 3 HBV DNA <300 copies/mL 0 Age 50-54 4 HBV DNA 300-9999 copies/mL 0 Age 55-59 5 HBV DNA 104 -99,000 copies/mL 3 Age 60-65 6 HBV DNA 105 - 999,999 copies/mL 5 HBV DNA > 106 copies/mL 4
Who cannot join
- • Patients who have confirmed HCC by CT/MRI when they enrolled. Patients who have previously had HCC but have been treated and have been recurrence free for 5 years are eligible.
- Patients with the other cancer(s)
- Pregnant Women
- Patients who have known diagnosis of mental incapacitation that affects their ability to consent.
- Patients who are likely to be transplanted within 1 year or MELD score greater than 20.
- Patients with total or direct bilirubin > 3x upper limit of normal
Show all 13Show fewer
- Patients with uncontrollable ascites
- Glomerular Filtration Rate less than 60.
- Patients with ≥ Grade II of hepatic encephalopathy
- Patients who are being treated with warfarin (DCP test values are affected by warfarin)
- Patients who have any contraindication to any of the study procedures, products used or its constituents (e.g., renal failure or contrast allergy).
- Patients who suffer from claustrophobia or who have other contraindications to MRI
- Patients with cirrhosis who were successfully treated for hepatitis C more than 3 years prior. However, patients who are on study who are treated for their hepatitis C may continue in the study.
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Toronto General Hospital
Toronto, Ontario, M5G 2C4
Toronto Western Hospital
Toronto, Ontario, M5T 2S8
About this study
Official title: A Randomized Controlled Trial to Determine the Role of Biomarkers in Surveillance for Hepatocellular Carcinoma (HCC)
The objective of this study is to evaluate the clinical effectiveness of biomarkers, alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP), for surveillance program patients whose hepatocellular carcinoma (HCC) development may be potentially missed by ultrasound (US). This study expects to demonstrate that addition of biomarkers will increase the detection rate by at least 10%.
Read the detailed description
This study is a prospective randomized controlled trial (RCT) comparing surveillance for hepatocellular carcinoma with ultrasound alone versus ultrasound and standard biomarkers. The study will be conducted initially at UHN (TGH and TWH). One arm will undergo surveillance for hepatocellular carcinoma using ultrasound (US) alone and the other will undergo HCC surveillance with US plus biomarkers (BM). The biomarkers to be used will be AFP, AFP-L3 and DCP). Subjects will undergo surveillance at 6 monthly intervals for a minimum of 2 years and up to 4 years. The endpoints will be the comparative effectiveness, defined as sensitivity and specificity of detection of HCC. The comparisons of sensitivity, specificity, and other parameters with respect to tumor characteristics will be made among US alone, biomarkers alone, and combined use of US and biomarkers. The target population is individuals who have liver cirrhosis and no HCC detectable at enrollment into the study. The factors contributing to the cause of the cirrhosis will be recorded but will not play a role into subject eligibility for the study
- Conditions
- Cirrhosis, Chronic Liver Diseases
- Keywords
- HCC, AFP, AFP-L3, DCP, Surveillance, biomarkers
- Medical subject headings
- Fibrosis
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 |
|---|---|---|
| Standard of care arm | Chronic liver disease patients who are under going standard of care surveillance for the development of HCC as defined by AASLD guidelines. | |
| Biomarker Arm | Chronic liver disease patients who are under going standard of care surveillance for the development of HCC as defined by AASLD guidelines plus the addition of biomarker assays (AFP, AFP-L3 and DCP) every 6 months. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biomarker assays exceeding threshold
Biomarker assay levels that exceed threshold will trigger diagnostic imaging for HCC. Ultrasound imaging indicating a suspicious nodule may also trigger diagnostic imaging.
Measured: Every 6 months until HCC is detected or up to 4 years
Secondary outcomes (1)
Surveillance until HCC development and detection
When the total number of HCC cases as diagnosed by CT/MRI have been observed. Approximately 300 cases in total half (150) the cases from each group
Measured: Up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2014 (estimated)
- Study startAug 2014
- Primary completionDec 2020
- Study completionFeb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CirrhosisStudies 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 2,500 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wako Life Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Feld Jordan, MD, Principal investigator, Toronto General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02272504
- Sponsor's protocol ID
- WLS 13-6926
- Status last verified
- Jul 2024
- First submitted
- 20 Oct 2014
- Last updated
- 23 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
Publications
Hirode G, Zangneh HF, Cerocchi O, Khalili K, El-Karim LA, Kandel C, Vecchio M, Winick J, Mori Y, Yamada H, Janssen HLA, Hansen BE, Sherman M, Feld JJ. Utility of Serum Biomarkers in Addition to Ultrasound for Early Detection of Hepatocellular Carcinoma in High-Risk Patients: A Randomized Controlled Trial. Gastroenterology. 2026 Mar;170(3):595-605. doi: 10.1053/j.gastro.2025.09.010. Epub 2026 Jan 20.
PubMed 41556856
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial to Determine the Role of Biomarkers in Surveillance for Hepatocellular Carcinoma (HCC)
- ClinicalTrials.gov ID
- NCT02272504
- Acronym / sponsor ID
- WLS 13-6926
- Conditions
- Cirrhosis, Chronic Liver Diseases
- Keywords
- HCC, AFP, AFP-L3, DCP, Surveillance, biomarkers
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 2,500 participants (actual)
- Lead sponsor
- Wako Life SciencesIndustry (pharma, biotech, devices)
- Study start
- Aug 2014
- Primary completion
- Dec 2020 (actual)
- Study completion
- Feb 2021 (actual)
- First posted
- 23 Oct 2014 (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 objective of this study is to evaluate the clinical effectiveness of biomarkers, alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP), for surveillance program patients whose hepatocellular carcinoma (HCC) development may be potentially missed by ultrasound (US). This study expects to demonstrate that addition of biomarkers will increase the detection rate by at least 10%.
Detailed description
This study is a prospective randomized controlled trial (RCT) comparing surveillance for hepatocellular carcinoma with ultrasound alone versus ultrasound and standard biomarkers. The study will be conducted initially at UHN (TGH and TWH). One arm will undergo surveillance for hepatocellular carcinoma using ultrasound (US) alone and the other will undergo HCC surveillance with US plus biomarkers (BM). The biomarkers to be used will be AFP, AFP-L3 and DCP). Subjects will undergo surveillance at 6 monthly intervals for a minimum of 2 years and up to 4 years. The endpoints will be the comparative effectiveness, defined as sensitivity and specificity of detection of HCC. The comparisons of sensitivity, specificity, and other parameters with respect to tumor characteristics will be made among US alone, biomarkers alone, and combined use of US and biomarkers. The target population is individuals who have liver cirrhosis and no HCC detectable at enrollment into the study. The factors contributing to the cause of the cirrhosis will be recorded but will not play a role into subject eligibility for the study
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard of care arm | – | –Chronic liver disease patients who are under going standard of care surveillance for the development of HCC as defined by AASLD guidelines. |
| Biomarker Arm | – | –Chronic liver disease patients who are under going standard of care surveillance for the development of HCC as defined by AASLD guidelines plus the addition of biomarker assays (AFP, AFP-L3 and DCP) every 6 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients who are at risk for the development of HCC as identified by the prior presence of chronic liver disease and cirrhosis.
Key inclusion criteria (5 listed)
- Patient who is able and willing to comply with study procedures, and signed and dated informed consent is obtained.
- Table 1 Variable Risk Score Variable Risk Score Male 2 ALT <15 0 Female 0 ALT 15-44 1 Age 30-34 0 ALT > 45 2 Age 35-39 1 HBeAg+ve 0 Age 40-44 2 Anti-HBe-positive 2 Age 45-49 3 HBV DNA <300 copies/mL 0 Age 50-54 4 HBV DNA 300-9999 copies/mL 0 Age 55-59 5 HBV DNA 104 -99,000 copies/mL 3 Age 60-65 6 HBV DNA 105 - 999,999 copies/mL 5 HBV DNA > 106 copies/mL 4
Key exclusion criteria (13 listed)
- • Patients who have confirmed HCC by CT/MRI when they enrolled. Patients who have previously had HCC but have been treated and have been recurrence free for 5 years are eligible.
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
Biomarker assays exceeding threshold
Time frame: Every 6 months until HCC is detected or up to 4 years
Biomarker assay levels that exceed threshold will trigger diagnostic imaging for HCC. Ultrasound imaging indicating a suspicious nodule may also trigger diagnostic imaging.
1 secondary outcome
Surveillance until HCC development and detection
Time frame: Up to 4 years
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 23 Jul 2024.
- Derived from this study: PubMed 41556856Hirode G, Zangneh HF, Cerocchi O, Khalili K, El-Karim LA, Kandel C, Vecchio M, Winick J, Mori Y, Yamada H, Janssen HLA, Hansen BE, Sherman M, Feld JJ. Utility of Serum Biomarkers in Addition to Ultrasound for Early Detection of Hepatocellular Carcinoma in High-Risk Patients: A Randomized Controlled Trial. Gastroenterology. 2026 Mar;170(3):595-605. doi: 10.1053/j.gastro.2025.09.010. Epub 2026 Jan 20.
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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.
Feld Jordan, MD principal investigator
Toronto General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cirrhosis and Chronic Liver Diseases, run by Wako Life Sciences at 2 sites in Canada.
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 5 inclusion and 13 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 23 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. 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?
Biomarker assays exceeding threshold (time frame: Every 6 months until HCC is detected or up to 4 years). 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 NCT02272504, which also lists 1 linked publication.
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 23 Jul 2024.