Reperfusion InjuryPhase 2CAPITLNCT02251041
Combined Drug Approach to Prevent Ischemia-reperfusion Injury During Transplantation of Livers (CAPITL)
A Phase 2 study testing Antithrombin-III, Infliximab and Apotransferrin in people with Reperfusion Injury, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Reperfusion Injury
- What is being tested?
- Antithrombin-III, Infliximab and Apotransferrin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 143 participants
- Where
- 1 siteBelgium
- Study dates
- Sep 2014to Aug 2019
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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,
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Combined Drug Approach to Prevent Ischemia-reperfusion Injury During Transplantation of Livers (CAPITL): a First-in-men Study
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.
Read the 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.
- Conditions
- Reperfusion Injury
- Being tested
- Antithrombin-III, Infliximab, Apotransferrin, Human recombinant erythropoietin, C1-Inhibitor
- Keywords
- Liver, Transplantation, Ischemia-reperfusion, Effectiveness
- Medical subject headings
- Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Antithrombin-IIIDrug
InfliximabDrug
ApotransferrinDrug
Human recombinant erythropoietinDrug
C1-InhibitorDrug
GlutathioneDrug
Alfa-tocopherolDrug
MelatoninDrug
EpoprostenolDrug
Sodium chloride solutionDrug
| Study group | Role | What they receive |
|---|---|---|
| cases | Active comparator | the group receives a combination of drugs Receives: 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) Receives: Drug: Sodium chloride solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: within 72 hours following liver transplantation
Secondary outcomes (10)
Graft Loss
graft loss at 3 and 12 months after liver transplantation
Measured: 3 and 12 months after liver transplantation
Recipient Death
recipient death at 3 and 12 months after liver transplantation
Measured: 3 and 12 months after liver transplantation
Early Graft Dysfunction
early graft dysfunction as defined by Olthoff
Measured: within first 7 days
Number of Participants Developing Biliary Strictures
Biliary strictures are the narrowing of the intrahepatic or extrahepatic biliary ductal system. Here we report the number of participants developing biliary strictures within 12 months post transplantation by MRCP (magnetic resonance cholangiopancreatography)
Measured: within 12 months post transplantation
Ischemia Reperfusion Injury Score
Ischemia Reperfusion Injury score 1h post reperfusion by using the Suzuki score and Monbaliu et al. The score ranges from 0 (no injury) to 4 (severe injury).
Measured: One hour post reperfusion
Graft Rejection
a liver biopsy will be taken after transplantation and in case of clinical suspicion of acute rejection
Measured: till 1 year after transplantation
Patients With at Least 1 Severe Surgical Complications
The ranking of surgical complications will be done by using Clavien-Dindo classification
Grade I Any deviation from the normal post-operative course not requiring surgical, endoscopic or radiological intervention. This includes the need for certain drugs (e.g. antiemetics, antipyretics, analgesics, diuretics and electrolytes), treatment with physiotherapy and wound infections that are opened at the bedside Grade II Complications requiring drug treatments other than those allowed for Grade I complications; this includes blood transfusion and total parenteral nutrition (TPN) Grade III Complications requiring surgical, endoscopic or radiological intervention Grade IV Life-threatening complications; this includes CNS complications (e.g. brain haemorrhage, ischaemic stroke, subarachnoid haemorrhage) which require intensive care, but excludes transient ischaemic attacks (TIAs) Grade V Death of the patient
A severe surgical complication is defined as Grade III or higher.
Measured: within 1 year after liver transplantation
Non-anastomotic Biliary Stricture
Non-anastomotic biliary stricture at 1 year
Measured: 1 year
Acute Kidney Injury Score
An acute kidney injury score of 1 indicates risk; 2, injury; and 3, failure. According to RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) Minimum score is 0 meaning there is no injury, maximum score is 3 meaning failure of the organ.
Measured: 48h
Post-Reperfusion Syndrome
Post-reperfusion syndrome defined as a 30% decrease of mean systemic blood pressure for more than 1 minute during the first 5 minutes following graft reperfusion
Measured: first 5 minutes following graft reperfusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2014 (estimated)
- Study startSep 2014
- Primary completionFeb 2019
- Study completionAug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Reperfusion InjuryStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 143 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Diethard Monbaliu, MD, PhD, Principal investigator, Abdominal transplant surgery - transplant coordination, Abdominal transplant surgery lab (microbiology & immunology Dpt)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02251041
- Sponsor's protocol ID
- CAPITL RCT
- Acronym
- CAPITL
- Status last verified
- Dec 2015
- First submitted
- 24 Sep 2014
- Last updated
- 23 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 19826248Vekemans 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.
PubMed 21987442Meurisse 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.
PubMed 36853611