Trial document




drksid header

  DRKS00021607

Trial Description

start of 1:1-Block title

Title

Laparoscopic Split-PVE vs. PVE alone for Generation of Hypertrophy Before Major Liver Resection - A randomized controlled trial

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

LAS VEGAS

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

[---]*

end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

Liver failure following liver surgery is a life-threatening complication. The risk of liver failure is directly linked to the liver volume following surgery. Therefore, various strategies were developed to increase the liver volume before surgery for safety reasons. The current standard of care is portal vein embolization (PVE) that blocks the blood flow to the liver sections which are planned to be removed and redirects the blood flow to the future liver remnant resulting in liver growth (=hypertrophy). An alternative approach is to divide the liver tissue surgically by a minimally-invasive approach (laparoscopic in-situ split) while the vessels remain intact and supplement the procedure with PVE. The liver surgery with removal of the affected liver sections will be performed subsequently if the desired volume of the future liver remnant is achieved. The present study is the first prospective study investigating which one of these two techniques is more efficient and safer for the patients. The study is planned as a randomized trial comparing laparoscopic in-situ split with PVE (=Split-PVE) to PVE alone with reference to the level of liver growth (=hypertrophy rate) at 10 days after PVE. Patients will be followed up for 24 months and surgical, oncological as well as outcomes of the quality of life will be assessed. In addition, blood and liver tissues will be collected during the study to evaluate the effect of liver growth in the study groups.

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

Portal vein embolization (PVE) is the standard of care for preoperative induction of liver hypertrophy and generates up to 43% hypertrophy rates of the future liver remnant (FLR) within 4 to 8 weeks. However, during the waiting period for hypertrophy, up to 40% of patients develop tumor progression and are no longer candidates for curative resections. An alternative approach to PVE is Associating Liver Partition and Portal vein Ligation for Staged hepatectomy (ALPPS) – a combination of hepatic transsection with portal vein ligation. Although the FLR hypertrophy is higher with ALPPS compared to PVE, this technique is associated with significant postoperative morbidity and mortality rates. Recently, minimally-invasive partial liver partitioning in combination with PVE (Split-PVE) was found to be an alternative technique to ALPPS by avoiding surgical dissection of the hepatic hilum in the first stage with potentially lower postoperative morbidity rates. Furthermore, Split-PVE is probably associated with a more pronounced liver hypertrophy compared to PVE alone due to occlusion of intrahepatic shunts. To date, no prospective trial has been performed evaluating the efficacy and safety of Split-PVE vs. PVE, as well as a laparoscopic approach of liver partitioning. Although there is rising evidence for a plateau of liver hypertrophy after 3-weeks of PVE, liver hypertrophy assessments following PVE are made typically 4-6 weeks following intervention with an increased risk of tumor progression. The present study was designed on the assumption that a minimum difference of 5% liver hypertrophy at 10 days is clinically relevant between the study groups.

end of 1:1-Block scientific synopsis
start of 1:1-Block forwarded Data

Do you plan to share individual participant data with other researchers?

No

end of 1:1-Block forwarded Data
start of 1:1-Block forwarded Data Content

Description IPD sharing plan:

[---]*

end of 1:1-Block forwarded Data Content
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00021607
  •   2020/04/29
  •   [---]*
  •   yes
  •   Approved
  •   2020-531N, Medizinische Ethik-Kommission II Medizinische Fakultät Mannheim der Universität Heidelberg
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  •   U1111-1251-0557 
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   C22 -  Malignant neoplasm of liver and intrahepatic bile ducts
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   Split-PVE: Patients randomized to the experimental group will undergo laparoscopic partial in-situ split in a standardized approach. Partial transection of the parenchyma (~50-60%) will be carried out without ligation of the portal vein. Subsequent PVE is carried out within 5±2 days after the liver partitioning.
  •   PVE: Patients randomized to the control group will undergo a portal vein embolization (PVE) in a standardized approach
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   N/A
  •   N/A
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

The degree of contralateral hypertrophy at 10 days following PVE is the primary endpoint. The FLR volume will be calculated in percentage as following: FLR (ml) / total liver volume (ml) x 100 = FLR (%). The degree of contralateral liver lobe hypertrophy (DH) is defined as the relative increase in volume of the FLR after PVE in both study groups calculated as following: FLRpost-PVE – FLRpre- PVE.

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

- Resectability rate
- Postoperative morbidity and mortality
- Timing of completion hepatic resection and delayed hepatic resection (days/weeks)
- Disease-free and overall survival at 24 months
- Differences in circulating biomarkers
- Differences in tissue-related biomarkers
- Patient-reported outcome

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   Germany
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  • University Medical Center 
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   Actual
  •   2020/07/27
  •   60
  •   Monocenter trial
  •   National
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional Inclusion Criteria

1) Indication for major hepatectomy confirmed by multi-disciplinary tumor conference
2) Insufficient future liver remnant of total liver volume, defined as:
- < 30% in patients with healthy liver parenchyma
- < 40% in patients with diseased liver parenchyma (e.g. chemotherapy-associated
steatohepatitis, non-alcoholic steatohepatitis, Child-A liver cirrhosis)
3) Age equal to or greater than 18 years
4) WHO/ECOG 0-2
5) Written informed consent

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

Exclusion Criteria

1) Child B or C liver cirrhosis
2) Portal vein thrombosis with complete luminal obstruction affecting the main trunk
3) Impaired mental state or language problems
4) Expected lack of compliance

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • Universitätsklinikum Mannheim
    • Theodor-Kutzer-Ufer 1-3
    • 68167  Mannheim
    • Germany
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address scientific-contact
    • Universität Heidelberg, Medizinische Fakultät Mannheim, Chirurgische Klinik
    • Mr.  PD Dr. med.  Emrullah  Birgin 
    • Theodor-Kutzer-Ufer 1-3
    • 68167  Mannheim
    • Germany
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address scientific-contact
    • Universität Heidelberg, Medizinische Fakultät Mannheim, Chirurgische Klinik
    • Mr.  Prof. Dr. med.  Nuh N.  Rahbari 
    • Theodor-Kutzer-Ufer 1-3
    • 68167  Mannheim
    • Germany
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Universität Heidelberg, Medizinische Fakultät Mannheim, Chirurgische Klinik
    • Mr.  PD Dr. med.  Emrullah  Birgin 
    • Theodor-Kutzer-Ufer 1-3
    • 68167  Mannheim
    • Germany
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    end of 1:1-Block address contact public-contact
  • start of 1:1-Block address public-contact
    • Universität Heidelberg, Medizinische Fakultät Mannheim, Chirurgische Klinik
    • Mr.  Prof. Dr. med.  Nuh N.  Rahbari 
    • Theodor-Kutzer-Ufer 1-3
    • 68167  Mannheim
    • Germany
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Universitätsklinikum Mannheim
    • Theodor-Kutzer-Ufer 1-3
    • 68167  Mannheim
    • Germany
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting ongoing
  •   [---]*
  •   [---]*
  •   [---]*
  •   [---]*
  •   [---]*
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

  • [---]*
end of 1:n-Block publications
* This entry means the parameter is not applicable or has not been set.