Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT06050200 |
| Other study ID # |
ABM24 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
May 2024 |
| Est. completion date |
May 2029 |
Study information
| Verified date |
September 2023 |
| Source |
Medical University of Warsaw |
| Contact |
Karolina Grat, PhD |
| Phone |
+48225992300 |
| Email |
karolina.grat[@]wum.edu.pl |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Liver resection is the treatment of choice in patients with malignant liver lesions.
Unfortunately, the surgery is not always an option, as in same patients the future remnant
liver (FRL) is too small to supply all the functions. Therefore, some additional methods have
been proposed to increase the size of the FRL.
The aim of this study is to compare the efficacy and safety of three methods of increasing
the future remnant liver - Portal Vein Embolization (PVE) - embolization of one of the portal
branches; Liver Vein Deprivation (LVD) - embolization both of the portal branch as well as
the hepatic vein; and partial ALPPS (Associating Liver Partition and Portal vein Ligation for
Staged hepatectomy) - ligation of portal vein branch with partial liver transection.
The efficacy of those three methods will be assessed both by analyzing the volumetric
increase (by computer tomography scans) and by functional increase (by 99mTc-mebrofenin
scintigraphy). Functional assessment of the liver hypertrophy seems to be of crucial
importance, as some of the previous studies suggest that there might be a significant
discrepancy in the increase of size comparing to the increase of function.
This is a prospective, interventional randomized study. The study group (154 patients) will
consist of patients being considered as candidates for major hepatic resection, after
inducing hypertrophy of the future remnant liver.
The primary study hypothesis is greater efficacy of ALPPS in preparing patients for large
hepatic resection by inducing hypertrophy of the future remnant liver, as compared both to
PVE and LVD.
In case of unsuccessful induction of hypertrophy by the embolization techniques, patients may
be qualified to rescue ALPPS procedure.
Primary end-point:
Percentage of patients with successful resection (patients, who gained sufficient increase of
the FRL to proceed to the liver resection) with no post-surgical 90-day mortality.
Secondary end-points:
1. the rate and degree of volume increase in different groups
2. the rate and degree of functional increase in different groups
3. CCI index and complication rate >=3 degree according to the Clavien-Dindo classification
after the first stage of treatment
4. CCI index and complication rate >=3 degree according to the Clavien-Dindo classification
after the second stage of treatment
5. overall duration of hospital stay
Patient will be randomly assigned to the three study groups. All patients will undergo an
abdominal contrast enhanced computed tomography and 99mTc-mebrofenin scintigraphy prior to
the first stage of treatment. During the first stage of treatment, patients will undergo,
according to their group:
1. Embolization of portal vein branch (PVE, portal vein embolization)
2. Embolization of both portal vein branch and hepatic vein (LVD, liver venous deprivation)
3. Partial ALPPS (Associating Liver Partition and Portal vein Ligation for Staged
hepatectomy) - ligation of portal vein branch with partial liver transection,
preferentially by laparoscopic technique Computed tomography scans and scintigraphy will
be repeated at day 7, 14 and 21 after the first stage of treatment. The second stage of
treatment, the liver resection, will be performed after achievement of sufficient
mebrofenin clearance rate (>=2,69%/min/m2). In case of failure to reach the desired
clearance rate, the measurements will be continued every 7 days up to day 42. In case of
uncertainty and discrepancy between the volumetric assessment in the computed tomography
scan and the mebrofenin scintigraphy, it will be allowed to proceed to stage two
(partial hepatectomy) after joint consultation of at least 3 hepatobiliary surgeons, 1
radiologist and 1 nuclear medicine specialist. Routine blood tests will be performed
according to the standard procedure in the Department, depending on the patient clinical
status. An additional blood sample will be collected from patients (after receiving and
additional informed consent from the patient) and will be stored in the biobank.
All patients will be monitored for surgical and 90-day complications. The volume increase
after first stage of treatment, the functional increase after first stage of treatment,
percentage of patients successfully proceeding to the second stage of treatment and
complication rate will be calculated.
The percentage of patients with complications >= 3 degree in Clavien-Dindo classification and
CCI index for each patient will be calculated.
Furthermore, the blood test results will be assessed to search for associations with
patients' outcomes. Any possible differences in terms of baseline patients characteristics
between groups will be addressed.
Statistical analysis will be performed using U Mann-Whitney test, exact Fisher's test,
logistic regression, general linear models, Kaplan-Meier method and log-rank test. All three
groups will be assessed in terms of occurrence of primary and secondary end-points.
Description:
Liver resection is the treatment of choice in patients with malignant liver lesions.
Unfortunately, the surgery is not always an option, as in same patients the future remnant
liver (FRL) is too small to supply all the functions. Therefore, some additional methods have
been proposed to increase the size of the FRL. Among the most widely used ones are: Portal
Vein Embolization (PVE) - embolization of one of the portal branches; Liver Vein Deprivation
(LVD) - embolization both of the portal branch as well as the hepatic vein and partial ALPPS
(Associating Liver Partition and Portal vein Ligation for Staged hepatectomy) - ligation of
portal vein branch with partial liver transection.
However, for the time being none of this methods has been proven to provide superior results
in comparison to other, and all of them are widely used in different centers. Most of the
previously published papers were retrospective in nature and as for now there was no
randomized trial conducted to compare all three of them. What is more, most of the previously
published papers focused on the volumetric increase, based solely on the computed tomography
analysis. The most important is however the functional increase, not the increase in size.
The functional increase can be assessed in the 99mTc-mebrofenin scintigraphy, which enables
to assess the liver function in a chosen part of the liver.
Some of the previously published papers indicate that there might be a significant
discrepancy in the increase of size comparing to the increase of function, which is
critically important in the clinical practice.
The aim of this study is to compare the efficacy and safety of three methods of increasing
the future remnant liver - PVE, LVD and ALPPS in patients in whom liver resection is
considered.
METHODS:
This is a prospective, interventional randomized study. Patients will be randomly assigned to
three groups in a 12:71:71 ratio: PVE, LVD and ALPPS groups, respectively.
Randomization will be performed directly after recruitment. The study group will consist of
patients being considered as candidates for major hepatic resection, after inducing
hypertrophy of the future remnant liver.
Inclusion criteria:
1. age >= 18 years
2. patients qualified for liver resection
3. future remnant liver <30% of standard liver volume
4. written informed consent
Exclusion criteria:
1. liver cirrhosis
2. pregnancy
3. poor general health status or comorbidities excluding general anesthesia or hepatic
resection
4. contraindications to iodine contrast agents
Hypothesis and study group:
The primary study hypothesis is greater efficacy of ALPPS in preparing patients for large
hepatic resection by inducing hypertrophy of the future remnant liver, as compared both to
PVE and LVD. Basing on previously published studies following success rates (as percentage of
patients completing the second stage of treatment, the hepatic resection) have been assumed:
57% for PVE, 73% for LVD and 91% for ALPPS.
Assuming the thresholds for type I and type II error of 5% and 20% respectively, the
calculated size of the study group should be 154 patients, more specifically 12 in the PVE
group, 71 in the LVD group and 71 in the ALPPS group.
Special surveillance will be applied to patients in the PVE group and in case of low efficacy
(<50%) in the first 6 patients, randomization to this group will be withheld.
Moreover, in case of unsuccessful induction of hypertrophy by the embolization techniques,
patients may be qualified to rescue ALPPS procedure.
Primary end-point:
Percentage of patients with successful resection (patients, who gained sufficient increase of
the FRL to proceed to the liver resection) with no post-surgical 90-day mortality.
Secondary end-points:
1. the rate and degree of volume increase in different groups
2. the rate and degree of functional increase in different groups
3. CCI index and complication rate >=3 degree according to the Clavien-Dindo classification
after the first stage of treatment
4. CCI index and complication rate >=3 degree according to the Clavien-Dindo classification
after the second stage of treatment
5. overall duration of hospital stay
Patient will be randomly assigned to the three study groups. All patients will undergo an
abdominal contrast enhanced computed tomography and 99mTc-mebrofenin scintigraphy prior to
the first stage of treatment. During the first stage of treatment, patients will undergo,
according to their group:
1. Embolization of portal vein branch (PVE, portal vein embolization)
2. Embolization of both portal vein branch and hepatic vein (LVD, liver venous deprivation)
3. Partial ALPPS (Associating Liver Partition and Portal vein Ligation for Staged
hepatectomy) - ligation of portal vein branch with partial liver transection,
preferentially by laparoscopic technique
Computed tomography scans and scintigraphy will be repeated at day 7, 14 and 21 after the
first stage of treatment. The second stage of treatment, the liver resection, will be
performed after achievement of sufficient mebrofenin clearance rate (>=2,69%/min/m2). In case
of failure to reach the desired clearance rate, the measurements will be continued every 7
days up to date 42. In case of uncertainty and discrepancy between the volumetric assessment
in the computed tomography scan and the mebrofenin scintigraphy, it will be allowed to
proceed to stage two (partial hepatectomy) after joint consultation of at least 3
hepatobiliary surgeons, 1 radiologist and 1 nuclear medicine specialist.
Routine blood tests such as morphology, serum bilirubin and creatinine concentration,
transaminase activity, gamma-glutamyltranspeptidase or INR will be performed according to the
standard procedure in the Department of Liver, Transplant and General Surgery, namely at day
0 and 1 and every 2-3 days or more frequent in the next days, depending on the patient
clinical status. An additional blood sample will be collected from patients (after receiving
and additional informed consent from the patient) and will be stored in the biobank
(according to "Quality Standards for Polish Biobanks" v.2.00). The samples will be stored at
the LBBK biobank at Medical University of Warsaw.
All patients will be monitored for surgical and 90-day complications. The volume increase
after first stage of treatment, the functional increase after first stage of treatment,
percentage of patients successfully proceeding to the second stage of treatment and
complication rate will be calculated.
The percentage of patients with complications >= 3 degree in Clavien-Dindo classification and
CCI index for each patient will be calculated.
Furthermore, the blood test results will be assessed to search for associations with
patients' outcomes. Any possible differences in terms of baseline patients characteristics
between groups will be addressed.
Statistical analysis will be performed using U Mann-Whitney test, exact Fisher's test,
logistic regression, general linear models, Kaplan-Meier method and log-rank test. All three
groups will be assessed in terms of occurrence of primary and secondary end-points.
The study is designed to last 6 years, from 1st June 2023 to 31st May 2029. The firsts four
months are planned for the initiation of the study, the following months for recruitment,
intervention and observation and the last two months for analyzing the results.
After discharge from the hospital, 2 control visit will be scheduled for each patient, 30 and
90 days after the liver resection. Further treatment will be continued in local oncological
centers.
