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

Universitaire Ziekenhuizen KU Leuven

Status and phase: Completed; Phase 2

Conditions: Reperfusion Injury

Treatments: Drug: Antithrombin-III; Drug: C1-Inhibitor; Drug: Alfa-tocopherol; Drug: Human recombinant erythropoietin; Drug: Glutathione; Drug: Epoprostenol; Drug: Sodium chloride solution; Drug: Apotransferrin; Drug: Melatonin; Drug: Infliximab

Study type: Interventional

Funder types: Other

Identifiers

NCT02251041

CAPITL RCT

Details and patient eligibility

About

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.

Full description

This unicentric, investigator-driven, open-label randomized clinical trial with 2 parallel arms was conducted in Belgium from September 2013 through February 2018, with 1-year follow-up. Adults wait-listed for a first solitary full-size liver transplant were screened for eligibility. Exclusion criteria were acute liver failure, kidney failure, contraindication to treatment, participation in another trial, refusal, technical issues, and death while awaiting transplant. Included patients were enrolled and randomized at the time of liver offer. Data were analyzed from May 20, 2019, to May 27, 2020.

Participants were randomized to a combined drug approach with standard of care (static cold storage) or standard of care only (control group). In the combined drug approach group, following static cold preservation, donor livers were infused with epoprostenol (ex situ, portal vein); recipients were given oral α-tocopherol and melatonin prior to anesthesia and intravenous antithrombin III, infliximab, apotransferrin, recombinant erythropoietin-β, C1-inhibitor, and glutathione during the anhepatic and reperfusion phase.

The primary outcome was the posttransplant peak serum aspartate aminotransferase (AST) level within the first 72 hours. Secondary end points were the frequencies of postreperfusion syndrome, ischemia-reperfusion injury score, early allograft dysfunction, surgical complications, ischemic cholangiopathy, acute kidney injury, acute cellular rejection, and graft and patient survival.

Enrollment: 143 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients suffering from irreversible liver failure eligible for liver transplantation according to Eurotransplant guidelines.
2. Patients > 18 years of age at time of listing on Eurotransplant waiting list for liver transplantation in University Hospitals Leuven, Belgium.

Exclusion criteria

1. Patients who refuse to participate in the study.

2. History of hypersensitivity to one/several component(s) of the combined drug approach.

3. 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.

4. Mental conditions rendering the subject incapable to understand the nature, scope, and consequences of the trial.

5. Combined organ transplantation.

6. Re-transplantation.

7. Patients that are dialysis-dependent prior to the liver transplantation.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

143 participants in 2 patient groups, including a placebo group

cases

Active Comparator group

Description:

the group receives a combination of drugs

Treatment:

Drug: Infliximab

Drug: Melatonin

Drug: Apotransferrin

Drug: Epoprostenol

Drug: Glutathione

Drug: Human recombinant erythropoietin

Drug: Alfa-tocopherol

Drug: C1-Inhibitor

Drug: Antithrombin-III

controls

Placebo Comparator group

Description:

the group do not receive a combination of drugs, but a placebo (sodium chloride solution)

Treatment:

Drug: Sodium chloride solution