Fast-track LiveR: Study for the Early Identification of Low-risk Patients After Partial Liver Resection by the LiMAx-test

Prospective, Randomized, Controlled, Multi-centric, Phase III Study for the Early Identification of Low-risk Patients After Partial Liver Resection by the LiMAx-test

The purpose of this study is to investigate safety and efficacy of intravenously injected 0.4% 13-C-Methacetin solution for the determination of liver function with the LiMAx-test on patients with partial liver resection. The LiMAx-test is compared with an untreated control group and post-surgical management of both groups is investigated.

Study Overview

• Status: Completed
• Conditions: Liver Failure
• Intervention / Treatment: Drug: 13-C-Methacetin

• Study Type: Interventional
• Enrollment (Actual): 149
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Dept. of General-, Visceral- and Graft Surgery, Charité Campus Virchow-Hospital
  • Jena, Germany, 07747
    • Dept. of General- and Visceral Surgery, Jena University Hospital
  • Leipzig, Germany, 04103
    • Clinic and Policlinic for Visceral-, Graft-, Thorax- and Vascular Surgery, Leipzig University Hospital
  • Würzburg, Germany, 97080
    • Clinic and Policlinic for General- Visceral- and Graft Surgery, Würzburg University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• male or female patients of 18 years or older which are able to give informed consent with indication for surgical partial liver resection according to OPS code 5-502; this includes benign and malign tumors.
• patients with pre-surgical thin-layer CT or MRT of the liver not older than 6 weeks or patients where a pre-surgical thin-layer CT or MRT of the liver is planned before surgery.
• written informed consent

Exclusion Criteria:

at screening:

• anamnestic known hypersensitivity against one of the study drugs, their ingredients or drugs with chemically similar structure (in particular paracetamol)
• participation in another clinical trials within 4 weeks before inclusion
• patients with previous liver surgery (OPS-Code 5-502), including biliodigestive anastomosis, excluding cholecystectomy.
• patients which underwent interventions such as radiofrequency ablation, biopsies or smaller surgeries within 6 weeks before inclusion
• patients anticipated for biliodigestive anastomosis and/or suffering from a Klatskin-tumor
• patients with a ASA (American Society of Anesthesiologists) classification >3
• patients anticipated for laparoscopic partial liver resection
• patients which are intended to be simultaneously treated with an interventional technique (e.g. radio frequency ablation RFA, embolization)
• patients which are intended to simultaneously get a surgery on other organs (excluding cholecystectomy)
• patients which are intended to simultaneously get a vascular anastomosis (e.g. portal vein resection)
• patients with known hepatic cirrhosis or known severe fibrosis (e.g. Ishak-score grade >4)
• patients with congenital metabolic diseases, in particular hepatic storage diseases
• hepatic infection with Echinococcus multilocularis
• patients with known non-infectious, auto-immune conditioned chronic inflammatory diseases (e.g. autoimmune hepatitis, Morbus Crohn, colitis ulcerativa)
• patients with severe cardiovascular diseases and/or severe diseases of the respiratory system which receive intensive care in any case (e.g. heart surgery, bypass surgery, cardiac valve replacement, unstable angina pectoris, severe coronary heart disease with intervention during the last 6 months, severe COPD (chronic obstructive pulmonary disease), severe asthma with concomitant cortisone medication)
• patients with severe bacterial infection at screening
• patients with known immunodeficiency
• heavy smokers (>20 cigarettes a day)
• patients which are unable to understand the study and its possible implications because of addiction or other diseases
• patients who are suspected not to cooperate or to comply to the trial protocol
• patients accommodated in an institution due to public or legal authority
• pregnant or lactating women
• women with child-bearing potential, excluding: negative pregnancy test and commitment to be sexually inactive until day 30 after surgery or discharge; postmenopause (12 months of natural occurring amenorrhoea); at least 6 weeks after ovariectomy with or without hysterectomy

at visit 2:

• patients anticipated for laparoscopic partial liver resection
• patients which are intended to be simultaneously treated with an interventional technique (e.g. radio frequency ablation RFA, embolization)
• patients which are intended to simultaneously get a surgery on other organs (excluding cholecystectomy)
• patients which are intended to simultaneously get a vascular anastomosis (e.g. portal vein resection)
• patients with known hepatic cirrhosis or known severe fibrosis (e.g. Ishak-score grade >4)
• hepatic infection with Echinococcus multilocularis
• patients with severe cardiovascular diseases and/or severe diseases of the respiratory system which receive intensive care in any case (e.g. heart surgery, bypass surgery, cardiac valve replacement, unstable angina pectoris, severe coronary heart disease with intervention during the last 6 months, severe COPD (chronic obstructive pulmonary disease), severe asthma with concomitant cortisone medication)
• patients anticipated for biliodigestive anastomosis and/or suffering from a Klatskin-tumor
• patients with a ASA (American Society of Anesthesiologists) classification >3

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LiMAx-group; Intravenous pre- and post-surgical injection of 0.4% 13-C-Methacetin solution. Dosage is adapted due to body weight (2 mg/kg). A LiMAx-test of >150 µg/kg/h would correspond to a general ward indication.	Drug: 13-C-Methacetin; intravenous injection of 0.4% 13-C-Methacetin solution, once before partial liver resection, once after partial liver resection
No Intervention: control group; Control group without intervention. Post-surgical management as defined prior to surgery following well-established clinical standards.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of correctly determined positive patients in each trial group	Correctly determined positive patients are patients which are transferred to general ward after surgery because of the result of the LiMAx-test (LiMAx-group) or general diagnosis (control group). Patients have to stay at general ward until discharge no later than day 30 after surgery.	no later than day 30 after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of incorrectly determined positive patients in each trial group	Incorrectly determined positive patients are patients which are transferred to general ward after surgery because of the result of the LiMAx-test or general diagnosis (control group) and do not stay at general ward until discharge or are discharged later than 30 days after surgery.	no later than day 30 after surgery
sensitivity	number of correctly predicted positive patients / (number of correctly predicted positive patients + number of incorrectly predicted negative patients)	1 year after trial start (anticipated December 2013)
specificity	number of correctly predicted negative patients / (number of correctly predicted negative patients + number of incorrectly predicted positive patients)	1 year after trial start (anticipated December 2013)
positive predictive value (PPV)	number of correctly predicted positive patients / (number of correctly predicted positive patients + number of incorrectly predicted positive patients)	1 year after trial start (anticipated December 2013)
negative predictive value (NPV)	number of correctly predicted negative patients / (number of correctly predicted negative patients + number of incorrectly predicted negative patients)	1 year after trial start (anticipated December 2013)
mortality	total mortality until day 30 post-surgical	1 year after trial start (anticipated December 2013)
number of patients with post-surgical liver failure (PHLF)	PHLF according to the Rahbari-Score	1 year after trial start (anticipated December 2013)
total number of complications	total number of complications of grade IIIa (surgical, endoscopic or radiological intervention) to grade V (death)	1 year after trial start (anticipated December 2013)
changes of routine laboratory data	assessment of clinical data (sodium, potassium, creatinine, urea, protein, albumin, total bilirubin, AST, ALT, AP, GGT, blood count, INR, PTT). In addition, clinical data as pulse or blood pressure are recorded.	until day 30 after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
pre- and post-surgical volumetric analysis of the liver	Pre-surgical volumetric analysis of liver and tumor by CT or MRT and post-surgical volumetric analysis of the resected liver.	immediately pre and post surgery

Collaborators and Investigators

• Sponsor: Humedics GmbH
• Investigators: Principal Investigator: Martin Stockmann, PD Dr. med., Dept. of General-, Visceral- and Graft Surgery, Charité Campus Virchow-Hospital, Augustenburger Platz 1, 13353 Berlin, Germany

Publications and helpful links

General Publications

• Stockmann M, Vondran FWR, Fahrner R, Tautenhahn HM, Mittler J, Bektas H, Malinowski M, Jara M, Klein I, Lock JF; Collaborative Fast-track Liver Study Group. Randomized clinical trial comparing liver resection with and without perioperative assessment of liver function. BJS Open. 2018 Jun 14;2(5):301-309. doi: 10.1002/bjs5.81. eCollection 2018 Sep.

Helpful Links

• EU clinical trials register with results

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2013
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: January 25, 2013
• First Submitted That Met QC Criteria: February 4, 2013
• First Posted (Estimate): February 7, 2013

Study Record Updates

• Last Update Posted (Actual): October 25, 2018
• Last Update Submitted That Met QC Criteria: October 23, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: liver function tests; 13-C-Methacetin; partial liver resection
• Additional Relevant MeSH Terms: Digestive System Diseases; Hepatic Insufficiency; Liver Diseases; Liver Failure
• Other Study ID Numbers: HUM-001