Combined Drug Approach to Prevent Ischemia-reperfusion Injury During Transplantation of Livers (CAPITL): a First-in-men Study
Overview
- Phase
- Phase 2
- Intervention
- Alfa-tocopherol
- Conditions
- Reperfusion Injury
- Sponsor
- Universitaire Ziekenhuizen KU Leuven
- Enrollment
- 143
- Locations
- 1
- Primary Endpoint
- Peak Aspartate Aminotransferase Within First 72h Post Transplant
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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.
Detailed 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.
Investigators
Eligibility Criteria
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.
Arms & Interventions
cases
the group receives a combination of drugs
Intervention: Alfa-tocopherol
cases
the group receives a combination of drugs
Intervention: Antithrombin-III
cases
the group receives a combination of drugs
Intervention: Infliximab
cases
the group receives a combination of drugs
Intervention: Apotransferrin
cases
the group receives a combination of drugs
Intervention: Human recombinant erythropoietin
cases
the group receives a combination of drugs
Intervention: C1-Inhibitor
cases
the group receives a combination of drugs
Intervention: Glutathione
cases
the group receives a combination of drugs
Intervention: Melatonin
cases
the group receives a combination of drugs
Intervention: Epoprostenol
controls
the group do not receive a combination of drugs, but a placebo (sodium chloride solution)
Intervention: Sodium chloride solution
Outcomes
Primary Outcomes
Peak Aspartate Aminotransferase Within First 72h Post Transplant
Time Frame: within 72 hours following liver transplantation
peak AST is defined as the highest value of serum AST within 72 hours following liver transplantation
Secondary Outcomes
- Early Graft Dysfunction(within first 7 days)
- Ischemia Reperfusion Injury Score(One hour post reperfusion)
- Acute Kidney Injury Score(48h)
- Non-anastomotic Biliary Stricture(1 year)
- Graft Loss(3 and 12 months after liver transplantation)
- Graft Rejection(till 1 year after transplantation)
- Recipient Death(3 and 12 months after liver transplantation)
- Number of Participants Developing Biliary Strictures(within 12 months post transplantation)
- Patients With at Least 1 Severe Surgical Complications(within 1 year after liver transplantation)
- Post-Reperfusion Syndrome(first 5 minutes following graft reperfusion)