Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05498779 |
| Other study ID # |
-A10492 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 1, 2022 |
| Est. completion date |
September 1, 2023 |
Study information
| Verified date |
November 2023 |
| Source |
Rigshospitalet, Denmark |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Background Hepatocellular carcinoma (HCC) is the most common primary malignancy in the liver.
Chronic infection with hepatitis C virus (HCV) is a significant risk factor and may be
associated with inferior outcome. According to the Danish national guidelines, ablation
should be offered patients with early HCC (tumor < 3 cm) in a cirrhotic liver, who are not
transplant candidates. However, the effect of size of the HCC tumor and Hepatitis C virus
(HCV) as etiology are insufficiently investigated.
Purposes
1. Investigate association between HCC tumor size and survival and recurrence after
ablation.
2. Investigate survival and recurrence after ablation in patients with HCV-related HCC
compared with HCC due to other etiologies.
Methods This study is based on data from the Danish Liver and Bile Duct Cancer Database
(DLGCD) and the Danish Database for Hepatitis B and C (DANHEP) and the laboratory database
(DANVIR), which collectively include information on patient characteristics, tumor
characteristic, laboratory results, and information regarding ablation, HCV status, and
antiviral treatment, respectively.
Perspectives Ablation has been widely used for decades, but studies investigating the effect
of ablation for HCC in patients with HCV and size of HCC are lacking. This study will
contribute considerably to the level of evidence and may impact both Danish and international
guidelines for HCC treatment.
Description:
Background Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver
and accounts for 85-90% of liver cancer. The most important risk factor for HCC is cirrhosis
of any etiology. Among other major risk factors for HCC are chronic viral infections with
hepatitis C virus (HCV) and hepatitis B virus (HBV), chronic alcohol consumption and
non-alcoholic steatohepatitis.
Three nationwide databases and medical records will be used to address these important
knowledge gaps. First, the association between survival and recurrence after ablation and HCC
tumor size will be investigated. Second, the survival and recurrence after ablation in
patients with HCC related to HCV will be investigated. due to HCV is different from that in
patients with HCC due to other reasons than HCV. The nationwide data in these databases will
reflect general clinical practice in an unselected population and provide novel information.
Purpose
With data from the Danish Liver and Bile Duct Cancer Database (DLGCD), the Danish Database
for Hepatitis B and C (DANHEP), the National hepatitis laboratory database (DANVIR), and
medical records, prognostic factors for survival in a large cohort of patients with HCC
treated with ablation therapy will be investigated with the following aims:
1. Investigate association between HCC tumor size and survival and recurrence after
ablation therapy.
2. Investigate survival and recurrence after ablation therapy in patients with HCV-related
HCC compared with HCC due to other etiologies.
Hypotheses
1. Survival and recurrence after ablation is lower in patients with large HCC tumors than
in patients with small tumors. However, the cut-off in current Danish guidelines is too
conservative.
2. The survival after ablation is lower in patients with HCC due to HCV than in patient
with HCC due to other reasons.
Methods This study is based on data from three large, nationwide databases in Denmark. DLGCD
is an ongoing prospective nationwide database for patients treated for HCC,
cholangiocarcinoma, colorectal liver metastases, or non-colorectal liver metastases. The
database was established in 2012 and started collecting data in 2013. So far, data from the
DLGCD have not been published. To date, the database includes data on 5056 surgical
procedures in 2975 patients with HCC. To study the effect of etiology on survival and
recurrence after treatment for HCC, data from the DANHEP and DANVIR databases will be
incorporated. The three databases can be linked together as they all use CPR number to
identify patients. DLGCD does not contain any information on HCV. However, DANHEP and DANVIR
are nationwide databases that contain detailed information on individuals with chronic viral
hepatitis in Denmark. DANHEP is a database with ongoing prospective registration of adult
patients treated at a hospital (outpatient or inpatient) with chronic viral hepatitis B or C,
established in 2002. DANVIR is a laboratory database containing information about HCV test
(bot positive and negative) since 1991. The observation period of the study will be from 2013
to 2022. With data from the DANHEP and DANVIR databases, patients with HCC that have been
infected with HCV can be identified to study the effect of ablation in HCV-infected patients
versus patients without HCV infection.
Statistics The dataset will be described with frequencies and percentages for categorical
variables and means or medians for continuous variables. For investigating differences,
Student's t -test or Mann-Whitney U for continuous data and Pearson chi2 or Fisher's exact
tests for categorical data will be used as appropriate. To determine risk factors affecting
prognosis, recurrence and survival outcomes after ablation, Cox proportional hazard
regression model will be used to calculate hazard ratios with 95% confidence intervals in
both univariable and multivariable analyses. The multivariable analysis will be adjusted for
age, sex, number of tumor, size of largest tumor, HCV-status, HBV-status, and Child-Pugh
score. In addition, survival will be estimated by Kaplan-Meier methods with log-rank tests
for HCV vs. non-HCV groups. It is possible that some patients with HCC never had a test for
HCV. In a sensitivity analysis, only patients with HCC that had a HCV test (positive or
negative) will be included. For recurrence we will use Fine-Gray proportional subhazards
model and Aalen-Johansen estimator with death and transplantation as competing risks. The
level of statistical significance will be set to p<0.05. All statistical analyses will be
performed using R, version 4.0.3.
Perspectives With data from nationwide databases, the aim is to investigate survival and
recurrence for HCC and the significance of tumor size and etiology of HCC in a large group of
patients. Ablation has been widely used for decades, but the majority of published studies
within this area are from Asia and based on small cohorts of highly selected patients.
Furthermore, to our knowledge, no previous larger studies have determined the effect of
ablation in patients with HCV-related HCC. Evidence will be improved with a large, Danish
cohort reflecting outcomes in general clinical practice in unselected patients. The study has
potential to contribute to the future guidelines regarding indication for ablation.
