Combined drug approach to prevent liver injury during transplantation.

Phase 1

• Conditions: Investigation of the ischemia-reperfusion injury in patients who will undergo a liver transplantation after receiving a drug combination/multifactorial modulation; Therapeutic area: Body processes [G] - Biological Phenomena [G16]

• Registration Number: EUCTR2012-001960-31-BE
• Lead Sponsor: Z Leuven

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-02-04
• Last Update Posted: 21 June 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 82

Inclusion Criteria

- Older than 18 years,
-Patients undergoing liver transplantation in University Hospitals Leuven, Centre Hospitalier Universitaire de Liège and at other national and international centers.
-Patient must have signed the patient informed consent,
-All donor types: donation after brain death (DBD), donation after cardiac death (DCD), standard criteria donors (SCD) and extended criteria donors (ECD) defined according Paris consensus

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

-Patients who refuse to participate in the study,
- History of hypersensitivity to anti-thrombin III (Atenativ®), C1-inhibitor (Cetor®/Cinryze®), melatonin (Circadin®), epoprostenol (Flolan®), recombinant human EPO (Neorecormon®), infliximab (Remicade®), glutathione (Tationil®), tocopferol (vitamin e suspension 100 mg/mL®) will be excluded from the treatment group.
- Conditions that prevent the use of the multifactorial modulation:
- Administration of heparin at therapeutic dose pre-operatively: anti-thrombin III (Atenativ®), epoprostenol (Flolan®).
- Congestive heart failure arising from severe left ventricular dysfunction: epoprostenol (Flolan®), infliximab (Remicade®).
- History of seizures (not related to the underlying liver disease or to metabolic disturbances secondary to liver cirrhoris and to be distuinghuised from e.g. hepatic encephalopathy), poorly controlled arterial hypertension, myocardial infarction or stroke in the month preceding the liver transplantation, and history of pre-existing venous thromboembolic disease which is not related to liver cirrhosis and hypercoagulability (eg. partial, complete or previous vena porta thrombosis/ vena mesenterica thrombosis/ vena lienalis): recombinant human EPO (Neorecormon®).
- Unstable angina pectoris: recombinant human EPO (Neorecormon®).
- Severe untreated infections such as sepsis, abscesses and opportunistic infections: infliximab (Remicade®).
- Use of Vitamin K antagonist anticoagulation preoperatively which can not be reversed, women taking oral contraceptives containing oestrogens: tocopferol (vitamin E suspension 100 mg/mL®).
- Patients with previous treatment of infliximab (Remicade®),
Mental conditions rendering the subject incapable to understand the nature, scope, and consequences of the trial,
- Combined organ transplantation,
- Re-transplantation,
- Patients that are dialysis-dependent prior to LTx,
- LTx from a living or a split organ donation
- Administration of the multifactorial modulation technically non-feasible (i.e impossibility to place the second central catheter required for the separate and sequential injection of the different components of the multifactorial modulation).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate <br>- the safety of the drug combination/multifactorial modulation<br>- the effectiveness of the drug combination/multifactorial modulation in reducing the peak of aspartate amino transferase (AST) – a surrogate marker of ischemia-reperfusion injury (IRI) - after liver transplantation.<br>;Secondary Objective: not applicable;Primary end point(s): The primary endpoint is the log-transformed peak AST, where peak AST is defined as the highest value of serum AST within 72 hours following liver transplantation.;Timepoint(s) of evaluation of this end point: -day of transplantation (= baseline)<br>-before hepatectomy<br>-before reperfusion<br>-30,60,120 minutes after reperfusion<br>-6,12,24,48,72 hours after reperfusion<br>