Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05800561 |
| Other study ID # |
368/20 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2022 |
| Est. completion date |
January 31, 2024 |
Study information
| Verified date |
March 2023 |
| Source |
Federico II University |
| Contact |
Roberto I Troisi, Md, PhD |
| Phone |
+390817462776 |
| Email |
roberto.troisi[@]unina.it |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
AIMS To evaluate the accuracy of HVPG (direct method), ICG-R15 and LSM/SSM (non-invasive
methods) in predicting the risk of PHLF and hepatic decompensation; to evaluate the
correlation between hepatic functional reserve (ICG-R15) and degree of portal hypertension
(HVPG) and LSM/SSM in Child Pugh 0, A and B cirrhotic patients; to evaluate the real weight
of HVPG in a multivariate analysis.
METHODS: Multicentric observational prospective study. INCLUSION CRITERIA: All patients with
liver cirrhosis with indication for surgical resection for hepatocellular carcinoma are
considered eligible. Patients will be selected for surgery based on standard criteria of
participating centers and on Child-Pugh score 0, A or B.
EXCLUSION CRITERIA: Patients undergoing emergency surgery; inability to understand informed
consent.
Primary endpoint: Comparison of the predictive accuracy (evaluated as Area Under The Curve of
the ROC curve, see statistics) of HVPG, ICG and Liver and Spleen Stiffness of Post-operative
Hepatic Failure (PHLF, according to ISGLS).
Secondary endpoints: - Predictive accuracy of HVPG, ICG-R15, LSM and SSM on postoperative
morbidity at 90 days according to the classification of Clavien-Dindo and to the
Comprehensive Complication Index (CCI), and on cirrhosis decompensation at 3 months after
surgery.
Description:
BACKGROUND: Most of current guidelines for the treatment of Hepatocellular Carcinoma (HCC)
are based on the Barcelona Clinic Liver Cancer (BCLC) staging system1, where Portal
Hypertension (PHT) alone contraindicates surgery2. However, the evolution of surgical
techniques and patient management has led many centers to overcome the limits proposed by
BCLC3, highlighting the need for new criteria and to consider additional factors tailored on
each patient4,5. Almost all papers analyzing the prognostic role of PHT in patients
undergoing liver surgery are based on retrospective data and on an indirect assessment of the
presence of PHT, that have been shown to have less prognostic role7. Among the indirect
methods of PHT assessment, hepatic elastography using FibroScan® has been recently
consolidated. LSM is known to be related to postoperative outcomes, but its impact on the
subset of PHT patients, as well as a comparison with SSM or HPVG, has never been
investigated. Given the splenic congestion secondary to PHT, new diagnostic algorithms for
CSPH take into account the spleen stiffness (SSM, with 46kPa cut-off)8. SSM has also been
shown to be related to post-operative outcomes9. In the pre-operative evaluations on the
extent of resection a key role is played by the hepatic functional reserves estimated with
the blood retention at 15 'of Indocyanine Green (ICG-R15). It has been proposed a
relationship between ICG blood levels and hepatic venous pressure gradient (HVPG), even if
only in Child A patients6. ICG-r15' has never been compared to LSM and SSM for postoperative
outcomes.
AIMS To evaluate the accuracy of HVPG (direct method), ICG-R15 and LSM/SSM (non-invasive
methods) in predicting the risk of PHLF and hepatic decompensation; to evaluate the
correlation between hepatic functional reserve (ICG-R15) and degree of portal hypertension
(HVPG) and LSM/SSM in Child Pugh 0, A and B cirrhotic patients; to evaluate the real weight
of HVPG in a multivariate analysis that takes into account patient demographics, CHILD, MELD,
tumor characteristics, extent of surgery, blood loss, invasiveness of the approach, LSM, SSM.
METHODS: Multicentric prospective study. INCLUSION CRITERIA: All patients with liver
cirrhosis with indication for surgical resection for hepatocellular carcinoma are considered
eligible. Patients will be selected for surgery based on standard criteria of participating
centers and on Child-Pugh score 0, A or B. EXCLUSION CRITERIA: Patients undergoing emergency
surgery; inability to understand informed consent. Primary endpoint: Comparison of the
predictive accuracy (evaluated as Area Under The Curve of the ROC curve, see statistics) of
HVPG, ICG and Liver and Spleen Stiffness of Post-operative Hepatic Failure (PHLF, according
to ISGLS). Secondary endpoints: - Predictive accuracy of HVPG, ICG-R15, LSM and SSM on
postoperative morbidity at 90 days according to the classification of Clavien-Dindo and to
the Comprehensive Complication Index (CCI), and on cirrhosis decompensation at 3 months after
surgery. Statistic analysis Comparisons between groups will be performed using student's T
test or Wilcoxon's rank test for continuous data, depending on the distribution of the
variable. Categorical data will be compared by using Pearson's Chi Square test. The presence
of a linear correlation between variables will be verified by linear regression. The accuracy
of a continuous variable in predicting a categorical outcome will be evaluated using the
Receiver Operating Characteristic (ROC) curves. The value of the area under the curve (AUC),
will be used as an index of predictive accuracy. The comparison between the AUC of different
variables will be performed by the method described by Hanley et al. A univariate and
multivariate analysis will also be performed including risk factors for surgery in cirrhotic
patients, including also LSM and SSM.
