Ignite Creation Date:
2024-05-06 @ 7:33 PM
Last Modification Date:
2024-10-26 @ 3:09 PM
Study NCT ID:
NCT06050200
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-05-08
First Post:
2023-08-31
Brief Title:
TANGO-LIVER Three Arm Nuclear Growth Observation in Liver Surgery
Sponsor:
Medical University of Warsaw
Organization:
Medical University of Warsaw
Study Overview
Official Title:
Comparison of Three Methods of Inducing Liver Hypertrophy Before Resection - a Randomized Controlled Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2023-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
TANGO-LIVER
Brief 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 269minm2 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 Fishers 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 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 269minm2 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 Fishers 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
Detailed 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 127171 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 269minm2 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 v200 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 Fishers 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
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 127171 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 269minm2 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 v200 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 Fishers 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None