CirrhosisPearlNCT05541601
Prospective Cohort for Early Detection of Liver Cancer
An observational study of Cirrhosis and Hepatocellular Carcinoma, run by University of Oxford at 1 site in United Kingdom.
Trial summary
This study aims to recruit 3000 people with liver cirrhosis into a Prospective cohort for early detection of Liver cancer - the Pearl cohort. The study team believe that using a combination of novel tests may improve the detection of early Hepatocellular Carcinoma (HCC). Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Cirrhosis, Hepatocellular Carcinoma
- What is being tested?
- Blood and Urine samples
- How many people
- 3,000 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 23 Feb 2022to Jul 2037
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 100 years
- All sexes
- Adult, Older adult
Study population: Patients with Child-Pugh (CP) A or B cirrhosis with no current or historical diagnosis of HCC. Diagnosis of cirrhosis can be based on, laboratory, imaging or histology criteria (e.g. the latter including Ishak stage >=5). Participants can be recruited to other interventional studies for treatment of cirrhosis or prevention of HCC prior to or during participation in the Pearl study.
Who may be able to join
- Patients of all genders, age >18 years
- Participant is willing and able to give informed consent for participation in the study.
- Evidence of cirrhosis CP A or B (as defined below, cirrhosis ever diagnosed), with an underlying aetiology of at least one of the following: chronic Hepatitis B Virus (HBV) infection, chronic Hepatitis C Virus (HCV) infection, alcoholic liver disease, non-alcoholic fatty liver disease or haemochromatosis
- Cirrhosis Diagnosis Definition
- Histological assessment (Ishak stage 5 or 6) or
- At least one of the following:
Show all 12Show fewer
- Validated non-invasive marker of fibrosis including fibroscan, AST to Platelet Ratio Index (APRI) score >2 or Enhanced Liver Fibrosis (ELF) score >10.48 or Fibrotest score >0.73. Fibroscan readings should be assessed by aetiology as below:
- HBV: >=10 kPa
- HCV: >=14.5 kPa
- Alcoholic Liver Disease (ALD): >=19.5 kPa
- Non-alcoholic fatty liver disease (NAFLD): >=15 kPa
- Haemochromatosis: >=12kPa ii. Evidence of varices at endoscopy or imaging in the context of a patent portal vein iii. Definitive radiological evidence of cirrhosis (i.e. nodularity of liver and splenomegaly on Ultrasound/CT)
Who cannot join
- Diagnosis of current OR historical hepatocellular carcinoma
- Liver transplant recipients or patients on active listing for liver transplantation
- Child-Pugh C cirrhosis
- In the view of the clinician, if the patient has a co-morbidity likely to lead to death within the following 12 months
- In the view of the clinician, if the patient was not thought to be suitable for HCC surveillance
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Study Coordinator contact
United Kingdom1 site, 1 recruiting
- Recruiting
Hepatology Clinical Trial Unit, John Radcliffe Hospital
Oxford, Oxfordshire, OX3 9DU
Eleanor Barnes, Prof, ellie.barnes@ndm.ox.ac.uk
About this study
This study aims to recruit 3000 people with liver cirrhosis into a Prospective cohort for early detection of Liver cancer - the Pearl cohort. The study team believe that using a combination of novel tests may improve the detection of early Hepatocellular Carcinoma (HCC).
Read the detailed description
During a four-year follow-up period, around 100 Pearl patients are expected to be diagnosed with HCC. Blood, urine, clinical and imaging data will be collected over the follow up period. The samples will be used to identify a range of tests (including genetic, protein and other biomarkers), which along with the clinical data will hopefully identify those most at risk of developing HCC, and to identify HCC at the earliest possible time points.
- Conditions
- Cirrhosis, Hepatocellular Carcinoma
- Being tested
- Blood and Urine samples
- 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.
Blood and Urine samplesOther
The samples will be used to identify a range of tests (including genetic, protein and other biomarkers), which along with the clinical data will hopefully identify those most at risk of developing HCC, and to identify HCC at the earliest possible time points.
| Study group | Role | What they receive |
|---|---|---|
| Pearl Cohort | All 3000 patients recruited to the Pearl study Receives: Other: Blood and Urine samples |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sensitivity of novel diagnostic approaches for the early diagnosis of HCC in enrolled patients who are diagnosed with HCC by conventional approaches.
Diagnostic approaches to be tested will include:
- detection of epigenetic (e.g. methylation profiling) and genetic mutations, and copy number variations in circulating tumour DNA;
- multiparametric MRI liver imaging including MR biomarkers of inflammation, fibrosis, fat and iron content;
- host genetic makeup (relevant variants identified through Genome Wide Association Studies);
- detection of autoantibodies to tumour associated antigens;
- epitope mapping of circulating antibody repertoire using random peptide libraries;
- protein biomarkers including the L3 isoform of alphafetoprotein, and des-gammacarboxy- prothrombin;
- proteomic and metabolomic profiling, including steroid metabolic signatures in urine.
Measured: When 50 cases of HCC have accumulated through to study completion; up to 5 years
Specificity of novel diagnostic approaches for the early diagnosis of HCC in enrolled patients who are diagnosed with HCC by conventional approaches.
Diagnostic approaches to be tested will include:
- detection of epigenetic (e.g. methylation profiling) and genetic mutations, and copy number variations in circulating tumour DNA;
- multiparametric MRI liver imaging including MR biomarkers of inflammation, fibrosis, fat and iron content;
- host genetic makeup (relevant variants identified through Genome Wide Association Studies);
- detection of autoantibodies to tumour associated antigens;
- epitope mapping of circulating antibody repertoire using random peptide libraries;
- protein biomarkers including the L3 isoform of alphafetoprotein, and des-gammacarboxy- prothrombin;
- proteomic and metabolomic profiling, including steroid metabolic signatures in urine.
Measured: When 50 cases of HCC have accumulated through to study completion; up to 5 years
Positive/Negative predictive values of novel diagnostic approaches for the early diagnosis of HCC in enrolled patients who are diagnosed with HCC by conventional approaches.
Diagnostic approaches to be tested will include:
- detection of epigenetic (e.g. methylation profiling) and genetic mutations, and copy number variations in circulating tumour DNA;
- multiparametric MRI liver imaging including MR biomarkers of inflammation, fibrosis, fat and iron content;
- host genetic makeup (relevant variants identified through Genome Wide Association Studies);
- detection of autoantibodies to tumour associated antigens;
- epitope mapping of circulating antibody repertoire using random peptide libraries;
- protein biomarkers including the L3 isoform of alphafetoprotein, and des-gammacarboxy- prothrombin;
- proteomic and metabolomic profiling, including steroid metabolic signatures in urine.
Measured: When 50 cases of HCC have accumulated through to study completion; up to 5 years
Secondary outcomes (2)
To develop models that can be used to "risk-stratify" cirrhosis patients according to their future risk of HCC
The Harrell's Concordance Index (C-index) will be calculated for each biomarker/model of interest. The minimum and maximum C-index scores are 0 and 1, respectively, where the higher the score the better the biomarker/model is at identifying HCC risk. C-index values indicate the degree to which individuals who develop HCC have a higher risk score than those who do not. C-index values will be adapted to incorporate non-HCC mortality as a competing risk. The C-index value will be used to identify the biomarkers/models with the best discriminative ability.
Measured: Throughout study to completion; 5 years
To better understand the incidence of HCC in a UK population stratified by underlying cirrhosis aetiology
Cumulative incidence of HCC according to cirrhosis aetiology
Measured: At 1, 3 and 5 year post- baseline.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2022
- Study start23 Feb 2022
- Primary completionJul 2037 (estimated)
- Study completionJul 2037 (estimated)
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.
- More trials run by University of OxfordThe 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
- 3,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Cancer Research UK, Roche Diagnostic Ltd., OncImmune Ltd, Perspectum, University of Nottingham, Glasgow Caledonian University
- Responsible party
- Sponsor
- Investigators
- Ellie Barnes, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05541601
- Sponsor's protocol ID
- Pearl
- Acronym
- Pearl
- Status last verified
- Sep 2022
- First submitted
- 1 Aug 2022
- Last updated
- 15 Sep 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Khanna K, Barnes E, Benselin J, Culver E, Irving W, Innes H, Pavlides M, Consortium D. Prospective cohort for early detection of liver cancer (Pearl): a study protocol. BMJ Open. 2024 Oct 1;14(10):e085541. doi: 10.1136/bmjopen-2024-085541.
PubMed 39353693
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Cohort for Early Detection of Liver Cancer
- ClinicalTrials.gov ID
- NCT05541601
- Acronym / sponsor ID
- Pearl / Pearl
- Conditions
- Cirrhosis, Hepatocellular Carcinoma
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 3,000 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Cancer Research UK, Roche Diagnostic Ltd., OncImmune Ltd, Perspectum, University of Nottingham, Glasgow Caledonian University
- Study start
- 23 Feb 2022 (actual)
- Primary completion
- Jul 2037 (estimated)
- Study completion
- Jul 2037 (estimated)
- First posted
- 15 Sep 2022 (actual)
- 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.
This study aims to recruit 3000 people with liver cirrhosis into a Prospective cohort for early detection of Liver cancer - the Pearl cohort. The study team believe that using a combination of novel tests may improve the detection of early Hepatocellular Carcinoma (HCC).
Detailed description
During a four-year follow-up period, around 100 Pearl patients are expected to be diagnosed with HCC. Blood, urine, clinical and imaging data will be collected over the follow up period. The samples will be used to identify a range of tests (including genetic, protein and other biomarkers), which along with the clinical data will hopefully identify those most at risk of developing HCC, and to identify HCC at the earliest possible time points.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pearl Cohort | – | Other: Blood and Urine samplesAll 3000 patients recruited to the Pearl study |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Patients with Child-Pugh (CP) A or B cirrhosis with no current or historical diagnosis of HCC. Diagnosis of cirrhosis can be based on, laboratory, imaging or histology criteria (e.g. the latter including Ishak stage >=5). Participants can be recruited to other interventional studies for treatment of cirrhosis or prevention of HCC prior to or during participation in the Pearl study.
Key inclusion criteria (12 listed)
- Patients of all genders, age >18 years
- Participant is willing and able to give informed consent for participation in the study.
- Evidence of cirrhosis CP A or B (as defined below, cirrhosis ever diagnosed), with an underlying aetiology of at least one of the following: chronic Hepatitis B Virus (HBV) infection, chronic Hepatitis C Virus (HCV) infection, alcoholic liver disease, non-alcoholic fatty liver disease or haemochromatosis
- Cirrhosis Diagnosis Definition
- Histological assessment (Ishak stage 5 or 6) or
Key exclusion criteria (5 listed)
- Diagnosis of current OR historical hepatocellular carcinoma
- Liver transplant recipients or patients on active listing for liver transplantation
- Child-Pugh C cirrhosis
- In the view of the clinician, if the patient has a co-morbidity likely to lead to death within the following 12 months
- In the view of the clinician, if the patient was not thought to be suitable for HCC surveillance
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 |
|---|---|---|
| Blood and Urine samplesThe samples will be used to identify a range of tests (including genetic, protein and other biomarkers), which along with the clinical data will hopefully identify those most at risk of developing HCC, and to identify HCC at the earliest possible time points. | Other | Pearl Cohort |
Primary outcome
Sensitivity of novel diagnostic approaches for the early diagnosis of HCC in enrolled patients who are diagnosed with HCC by conventional approaches.
Time frame: When 50 cases of HCC have accumulated through to study completion; up to 5 years
Diagnostic approaches to be tested will include: 1. detection of epigenetic (e.g. methylation profiling) and genetic mutations, and copy number variations in circulating tumour DNA; 2. multiparametric MRI liver imaging including MR biomarkers of inflammation, fibrosis, fat and iron content; 3. host genetic makeup (relevant variants identified through Genome Wide Association Studies); 4. detection of autoantibodies to tumour associated antigens; 5. epitope mapping of circulating antibody repertoire using random peptide libraries; 6. protein biomarkers including the L3 isoform of alphafetoprotein, and des-gammacarboxy- prothrombin; 7. proteomic and metabolomic profiling, including steroid metabolic signatures in urine.
Specificity of novel diagnostic approaches for the early diagnosis of HCC in enrolled patients who are diagnosed with HCC by conventional approaches.
Time frame: When 50 cases of HCC have accumulated through to study completion; up to 5 years
Diagnostic approaches to be tested will include: 1. detection of epigenetic (e.g. methylation profiling) and genetic mutations, and copy number variations in circulating tumour DNA; 2. multiparametric MRI liver imaging including MR biomarkers of inflammation, fibrosis, fat and iron content; 3. host genetic makeup (relevant variants identified through Genome Wide Association Studies); 4. detection of autoantibodies to tumour associated antigens; 5. epitope mapping of circulating antibody repertoire using random peptide libraries; 6. protein biomarkers including the L3 isoform of alphafetoprotein, and des-gammacarboxy- prothrombin; 7. proteomic and metabolomic profiling, including steroid metabolic signatures in urine.
Positive/Negative predictive values of novel diagnostic approaches for the early diagnosis of HCC in enrolled patients who are diagnosed with HCC by conventional approaches.
Time frame: When 50 cases of HCC have accumulated through to study completion; up to 5 years
Diagnostic approaches to be tested will include: 1. detection of epigenetic (e.g. methylation profiling) and genetic mutations, and copy number variations in circulating tumour DNA; 2. multiparametric MRI liver imaging including MR biomarkers of inflammation, fibrosis, fat and iron content; 3. host genetic makeup (relevant variants identified through Genome Wide Association Studies); 4. detection of autoantibodies to tumour associated antigens; 5. epitope mapping of circulating antibody repertoire using random peptide libraries; 6. protein biomarkers including the L3 isoform of alphafetoprotein, and des-gammacarboxy- prothrombin; 7. proteomic and metabolomic profiling, including steroid metabolic signatures in urine.
2 secondary outcomes
To develop models that can be used to "risk-stratify" cirrhosis patients according to their future risk of HCC
Time frame: Throughout study to completion; 5 years
To better understand the incidence of HCC in a UK population stratified by underlying cirrhosis aetiology
Time frame: At 1, 3 and 5 year post- baseline.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2022.
- Derived from this study: PubMed 39353693Khanna K, Barnes E, Benselin J, Culver E, Irving W, Innes H, Pavlides M, Consortium D. Prospective cohort for early detection of liver cancer (Pearl): a study protocol. BMJ Open. 2024 Oct 1;14(10):e085541. doi: 10.1136/bmjopen-2024-085541.
- DeLIVER Project WebsiteLink provided by the sponsor.
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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.
Study Coordinator contact
Ellie Barnes principal investigator
University of Oxford
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 and Hepatocellular Carcinoma, run by University of Oxford at 1 site in United Kingdom.
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 12 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: looking for participants now, as of the sponsor's last update on 15 Sep 2022. 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 United Kingdom. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Study Coordinator (deliver-pearl@ndm.ox.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sensitivity of novel diagnostic approaches for the early diagnosis of HCC in enrolled patients who are diagnosed with HCC by conventional approaches. (time frame: When 50 cases of HCC have accumulated through to study completion; up to 5 years). The study lists 3 primary outcomes in all. 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 NCT05541601, 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 15 Sep 2022.