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

NCT02251041 | Completed Phase 2 Results DMC

• 1 other identifier: CAPITL RCT
• Study Type: interventional
• Target: 143
• Locations: 1 country
• Sites: 1

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.

Conditions

Reperfusion Injury

Keywords

Liver; Transplantation; Ischemia-reperfusion; Effectiveness

Outcome Measures

Primary Outcomes (1)

• Peak Aspartate Aminotransferase Within First 72h Post Transplant

  peak AST is defined as the highest value of serum AST within 72 hours following liver transplantation

  within 72 hours following liver transplantation

Secondary Outcomes (10)

• Graft Loss

  3 and 12 months after liver transplantation

• Recipient Death

  3 and 12 months after liver transplantation

• Early Graft Dysfunction

  within first 7 days

• Number of Participants Developing Biliary Strictures

  within 12 months post transplantation

• Ischemia Reperfusion Injury Score

  One hour post reperfusion

Other Outcomes (1)

• Intensive Care Unit Length of Stay (Recipient)

  During hospital stay for liver transplantation

Study Arms (2)

cases

ACTIVE COMPARATOR

the group receives a combination of drugs

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

controls

PLACEBO COMPARATOR

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

Drug: Sodium chloride solution

Interventions

Antithrombin-III DRUG

cases

Infliximab DRUG

cases

Apotransferrin DRUG

cases

Human recombinant erythropoietin DRUG

cases

C1-Inhibitor DRUG

cases

Glutathione DRUG

cases

Alfa-tocopherol DRUG

cases

Melatonin DRUG

cases

Epoprostenol DRUG

cases

Sodium chloride solution DRUG

controls

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

University Hospitals Leuven

Leuven, 3000, Belgium

Location

Related Publications (3)

• 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.

  PMID: 19826248 BACKGROUND

• 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.

  PMID: 21987442 BACKGROUND

• Meurisse N, Mertens M, Fieuws S, Gilbo N, Jochmans I, Pirenne J, Monbaliu D. Effect of a Combined Drug Approach on the Severity of Ischemia-Reperfusion Injury During Liver Transplant: A Randomized Clinical Trial. JAMA Netw Open. 2023 Feb 1;6(2):e230819. doi: 10.1001/jamanetworkopen.2023.0819.

  PMID: 36853611 DERIVED

MeSH Terms

Conditions

Reperfusion Injury

Interventions

Antithrombin III; Infliximab; apotransferrin; Complement C1 Inhibitor Protein; Glutathione; Melatonin; Epoprostenol; Sodium Chloride

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antithrombin Proteins; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Alpha-Globulins; Serum Globulins; Blood Proteins; Proteins; Globulins; Blood Coagulation Factor Inhibitors; Biological Factors; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Glycoproteins; Glycoconjugates; Carbohydrates; Complement C1 Inactivator Proteins; Complement Inactivator Proteins; Complement System Proteins; Oligopeptides; Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Prostaglandins I; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Autacoids; Inflammation Mediators; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

* Single center RCT * Individual effects of each component of CDA in decreasing IRI were not assessed separately. * Despite the fact that CDA components were administrated according to a specific timing in relation to their pharmacokinetics with the aim to reach a peak concentration during reperfusion, blood levels of each component were not determined. * Although the study was powered to detect differences in peak AST, the small sample size did not allow a claim on the absence of an effect.

Results Point of Contact

• Title: Diethard Monbaliu
• Organization: UZLeuven

diethard.monbaliu@uzleuven.be

+32 16 348727

Study Officials

• Diethard Monbaliu, MD, PhD

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2014
• First Posted: September 26, 2014
• Study Start: September 1, 2014
• Primary Completion: February 1, 2019
• Study Completion: August 1, 2019
• Last Updated: August 23, 2024
• Results First Posted: August 23, 2024

Record last verified: 2015-12

Locations

BE (1)