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.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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
Are there results?: Yes, posted in the registrySummary in the doctors' view

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,

Show all 14Show fewer

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.

Belgium1 site

University Hospitals Leuven
Leuven, 3000

Other trials in Belgium

About this study

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

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 groups in NCT02251041
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.

Sep 2014Aug 2019

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)

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 19826248
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.
PubMed 21987442
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.
PubMed 36853611

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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New Biomarkers for Organ Viability Assessment During Hypothermic Machine Perfusion in Liver Transplantation: the Role of Extemporaneous Histological Examination.
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Active, not recruitingPhase 3
The Danish Out-of-Hospital Cardiac Arrest Study
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RecruitingPhase 2
Prevention of Reperfusion Injury Outcomes Through Effective Cardioprotection Targeting Myocardial Infarction
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Recruiting
Rapid Local Ischemic Postconditioning on Stroke After Thrombectomy
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Recruiting
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All Reperfusion Injury trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Combined Drug Approach to Prevent Ischemia-reperfusion Injury During Transplantation of Livers (CAPITL): a First-in-men Study
ClinicalTrials.gov ID: NCT02251041
Acronym / sponsor ID: CAPITL / CAPITL RCT
Conditions: Reperfusion Injury
Keywords: Liver, Transplantation, Ischemia-reperfusion, Effectiveness
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 143 participants (actual)
Lead sponsor: Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
Study start: Sep 2014 (actual)
Primary completion: Feb 2019 (actual)
Study completion: Aug 2019 (actual)
First posted: 26 Sep 2014 (estimated)
Results: Posted 23 Aug 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (participant)
Number of arms: 2

Arm	Type	Receives
cases	Active comparator	Drug: Antithrombin-III, Drug: Infliximab, Drug: Apotransferrin, Drug: Human recombinant erythropoietin, Drug: C1-Inhibitor, Drug: Glutathione, Drug: Alfa-tocopherol, Drug: Melatonin, Drug: Epoprostenolthe group receives a combination of drugs
controls	Placebo comparator	Drug: Sodium chloride solutionthe group do not receive a combination of drugs, but a placebo (sodium chloride solution)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

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.

Key exclusion criteria (14 listed)

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:
Mental conditions rendering the subject incapable to understand the nature, scope, and consequences of the trial.
Combined organ transplantation.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
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

Primary outcome

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

10 secondary outcomes

Graft Loss
Time frame: 3 and 12 months after liver transplantation
Recipient Death
Time frame: 3 and 12 months after liver transplantation
Early Graft Dysfunction
Time frame: within first 7 days
Number of Participants Developing Biliary Strictures
Time frame: within 12 months post transplantation
Ischemia Reperfusion Injury Score
Time frame: One hour post reperfusion
Graft Rejection
Time frame: till 1 year after transplantation
Patients With at Least 1 Severe Surgical Complications
Time frame: within 1 year after liver transplantation
Non-anastomotic Biliary Stricture
Time frame: 1 year
Acute Kidney Injury Score
Time frame: 48h
Post-Reperfusion Syndrome
Time frame: first 5 minutes following graft reperfusion

Results and safety

Results posted to the registry on 23 Aug 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Combined Drug Approach	53	38
Controles	40	36

Primary outcome: Peak Aspartate Aminotransferase Within First 72h Post Transplant

Time frame: within 72 hours following liver transplantation. Geometric mean (95% Confidence Interval). Unit: U/L

Measure	Combined Drug Approach n = 36	Controles n = 36
Value	1262.9 (946.3 to 1685.4)	1451.2 (1087.4 to 1936.7)

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected over the time frame of 1 year starting immediately after transplantation. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Combined Drug Approach	6 of 36 (16.7%)	33 of 36 (91.7%)	4 of 36
Controles	4 of 36 (11.1%)	31 of 36 (86.1%)	3 of 36

Limitations and caveats (from the sponsor): * 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 19826248Monbaliu 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.
Background: PubMed 21987442Vekemans 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.
Derived from this study: PubMed 36853611Meurisse 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.

Related trials for Reperfusion Injury

Not yet recruiting
New Biomarkers for Organ Viability Assessment During Hypothermic Machine Perfusion in Liver Transplantation: the Role of Extemporaneous Histological Examination.
Liver Transplantation (LT), Early Allograft Dysfunction
Active, not recruitingPhase 3
The Danish Out-of-Hospital Cardiac Arrest Study
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RecruitingPhase 2
Prevention of Reperfusion Injury Outcomes Through Effective Cardioprotection Targeting Myocardial Infarction
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Recruiting
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Recruiting
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Diethard Monbaliu, MD, PhD principal investigator

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

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Peak Aspartate Aminotransferase Within First 72h Post Transplant (time frame: within 72 hours following liver transplantation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02251041, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2024.