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

Primary Purpose

Reperfusion Injury

Status

Completed

Phase

Phase 2

Locations

Belgium

Study Type

Interventional

Intervention

Antithrombin-III

Infliximab

Apotransferrin

Human recombinant erythropoietin

C1-Inhibitor

Glutathione

Alfa-tocopherol

Melatonin

Epoprostenol

Sodium chloride solution

About this trial

This is an interventional treatment trial for Reperfusion Injury focused on measuring Liver, Transplantation, Ischemia-reperfusion, Effectiveness

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University Hospitals Leuven

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

cases

controles

Arm Description

the group receives a combination of drugs

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

graft loss

graft loss at 3 and 12 months after liver transplantation

recipient death

recipient death at 3 and 12 months after liver transplantation

early graft dysfunction

early graft dysfunction as defined by Olthoff

Incidence of biliary strictures

Incidence of biliary strictures within 12 months post transplantation by MRCP (magentic resonance cholangiopancreatography)

IRI score

IRI score during transplantation, 1 week and 1 year after liver transplantation by using the Suzuki score and Monbaliu et al.

Graft rejecton

a liver biopsy will be taken after transplantation and in cas of clinical suspicion of acute rejection

Surgical complications

the ranking of surgical complications will be done by using Clavien-Dindo classification

Full Information

NCT ID

NCT02251041

First Posted

September 24, 2014

Last Updated

August 8, 2019

Sponsor

Universitaire Ziekenhuizen KU Leuven

1. Study Identification

Unique Protocol Identification Number

NCT02251041

Brief Title

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

Acronym

CAPITL

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2015

Overall Recruitment Status

Completed

Study Start Date

September 2014 (Actual)

Primary Completion Date

February 2019 (Actual)

Study Completion Date

August 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Universitaire Ziekenhuizen KU Leuven

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Reperfusion Injury

Keywords

Liver, Transplantation, Ischemia-reperfusion, Effectiveness

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Randomized

Enrollment

72 (Actual)

8. Arms, Groups, and Interventions

Arm Title

cases

Arm Type

Active Comparator

Arm Description

the group receives a combination of drugs

Arm Title

controles

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Antithrombin-III

Intervention Type

Drug

Intervention Name(s)

Infliximab

Intervention Type

Drug

Intervention Name(s)

Apotransferrin

Intervention Type

Drug

Intervention Name(s)

Human recombinant erythropoietin

Intervention Type

Drug

Intervention Name(s)

C1-Inhibitor

Intervention Type

Drug

Intervention Name(s)

Glutathione

Intervention Type

Drug

Intervention Name(s)

Alfa-tocopherol

Intervention Type

Drug

Intervention Name(s)

Melatonin

Intervention Type

Drug

Intervention Name(s)

Epoprostenol

Intervention Type

Drug

Intervention Name(s)

Sodium chloride solution

Primary Outcome Measure Information:

Title

log-transformed peak AST

Description

log-transformed peak AST, where peak AST is defined as the highest value of serum AST within 72 hours following liver transplantation

Time Frame

within 72 hours following liver transplantation

Secondary Outcome Measure Information:

Title

graft loss

Description

graft loss at 3 and 12 months after liver transplantation

Time Frame

3 and 12 months after liver transplantation

Title

recipient death

Description

recipient death at 3 and 12 months after liver transplantation

Time Frame

3 and 12 months after liver transplantation

Title

early graft dysfunction

Description

early graft dysfunction as defined by Olthoff

Time Frame

within first 7 days

Title

Incidence of biliary strictures

Description

Incidence of biliary strictures within 12 months post transplantation by MRCP (magentic resonance cholangiopancreatography)

Time Frame

within 12 months post transplantation

Title

IRI score

Description

IRI score during transplantation, 1 week and 1 year after liver transplantation by using the Suzuki score and Monbaliu et al.

Time Frame

during transplantation, 1 week and 1 year after

Title

Graft rejecton

Description

a liver biopsy will be taken after transplantation and in cas of clinical suspicion of acute rejection

Time Frame

till 1 year after transplantation

Title

Surgical complications

Description

the ranking of surgical complications will be done by using Clavien-Dindo classification

Time Frame

within 30 days after liver transplantation

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Diethard Monbaliu, MD, PhD

Organizational Affiliation

Abdominal transplant surgery - transplant coordination, Abdominal transplant surgery lab (microbiology & immunology Dpt)

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Hospitals Leuven

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

12. IPD Sharing Statement

Citations:

PubMed Identifier

19826248

Citation

Monbaliu D, Vekemans K, Hoekstra H, Vaahtera L, Libbrecht L, Derveaux K, Parkkinen J, Liu Q, Heedfeld V, Wylin T, Deckx H, Zeegers M, Balligand E, Buurman W, van Pelt J, Porte RJ, Pirenne J. Multifactorial biological modulation of warm ischemia reperfusion injury in liver transplantation from non-heart-beating donors eliminates primary nonfunction and reduces bile salt toxicity. Ann Surg. 2009 Nov;250(5):808-17. doi: 10.1097/SLA.0b013e3181bdd787.

Results Reference

background

PubMed Identifier

21987442

Citation

Vekemans K, Monbaliu D, Balligand E, Heedfeld V, Jochmans I, Pirenne J, van Pelt J. Improving the function of liver grafts exposed to warm ischemia by the Leuven drug protocol: exploring the molecular basis by microarray. Liver Transpl. 2012 Feb;18(2):206-18. doi: 10.1002/lt.22446.

Results Reference

background

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

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