Combined Drug Approach to Prevent Ischemia-reperfusion Injury During Transplantation of Livers (CAPITL)

Study Overview
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Brief Summary
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The purpose of this study is to establish the effectiveness of the combined drug approach (anti-thrombin III, infliximab, apotransferrin, human recombinant erythropoietin beta, C1-inhibitor, glutathione, alfa-tocopherol, melatonin and epoprostenol)aimed to reduce ischemia-reperfusion injury during liver transplantation in eligible recipients.

Official Title
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Combined Drug Approach to Prevent Ischemia-reperfusion Injury During Transplantation of Livers (CAPITL): a First-in-men Study

Conditions
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Reperfusion Injury

Intervention / Treatment
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* Drug: Antithrombin-III
* Drug: Infliximab
* Drug: Apotransferrin
* Drug: Human recombinant erythropoietin
* Drug: C1-Inhibitor
* Drug: Glutathione
* Drug: Alfa-tocopherol
* Drug: Melatonin
* Drug: Epoprostenol
* Drug: Sodium chloride solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients suffering from irreversible liver failure eligible for liver transplantation according to Eurotransplant guidelines. Patients > 18 years of age at time of listing on Eurotransplant waiting list for liver transplantation in University Hospitals Leuven, Belgium. Exclusion Criteria: Patients who refuse to participate in the study. History of hypersensitivity to one/several component(s) of the combined drug approach. Conditions that prevent the use of the combined drug approach: Administration of heparin at therapeutic dose pre-operatively, Congestive heart failure, History of seizure, poorly controlled arterial hypertension, myocardial infarction or stroke in the month preceding the liver transplantation, venous thromboembolic disease, Unstable angina pectoris, Sepsis, abcesses or opportunistic infections, History of infliximab treatment, Use of vitamin K antagonist anticoagulation. 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 the liver transplantation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: cases<br>the group receives a combination of drugs | Drug: Antithrombin-III<br> <br> Drug: Infliximab<br> <br> Drug: Apotransferrin<br> <br> Drug: Human recombinant erythropoietin<br> <br> Drug: C1-Inhibitor<br> <br> Drug: Glutathione<br> <br> Drug: Alfa-tocopherol<br> <br> Drug: Melatonin<br> <br> Drug: Epoprostenol<br> <br> |
| Placebo Comparator: controles<br>the group do not receive a combination of drugs, but a placebo (sodium chloride solution) | Drug: Sodium chloride solution<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| log-transformed peak AST | log-transformed peak AST, where peak AST is defined as the highest value of serum AST within 72 hours following liver transplantation | within 72 hours following liver transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| graft loss | graft loss at 3 and 12 months after liver transplantation | 3 and 12 months after liver transplantation | 
| recipient death | recipient death at 3 and 12 months after liver transplantation | 3 and 12 months after liver transplantation | 
| early graft dysfunction | early graft dysfunction as defined by Olthoff | within first 7 days | 
| Incidence of biliary strictures | Incidence of biliary strictures within 12 months post transplantation by MRCP (magentic resonance cholangiopancreatography) | within 12 months post transplantation | 
| IRI score | IRI score during transplantation, 1 week and 1 year after liver transplantation by using the Suzuki score and Monbaliu et al. | during transplantation, 1 week and 1 year after | 
| Graft rejecton | a liver biopsy will be taken after transplantation and in cas of clinical suspicion of acute rejection | till 1 year after transplantation | 
| Surgical complications | the ranking of surgical complications will be done by using Clavien-Dindo classification | within 30 days after liver transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver, Transplantation, Ischemia-reperfusion, Effectiveness