Liver Transplant FailureEASENCT03858088
Early Allograft Failure Simplified Estimation (EASE) in Liver Transplantation
An observational study of Liver Transplant Failure, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
Trial summary
A variety of clinical scores have been developed with the intent to predict early allograft failure after liver transplantation. With the present study the investigators aim to validate the recently published L-GrAFT Score on a multicenter cohort from 14 liver transplant centers in Italy. Read more about this study
- Who is it for?
- Ages 18 to 73 years
- Conditions the study is for
- Liver Transplant Failure
- What is being tested?
- Liver transplantation
- Type of treatment
- Surgery or procedure
- How many people
- 2,350 participants
- Where
- 1 siteItaly
- Study dates
- 15 Jun 2018to 10 Jan 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
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 to 73 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: A total of 1800 recipients of a primary liver transplant (LT) from 14 LT Centers from Italy (Training set) and 550 recipients of LT from 2 LT Centers from the United Kingdom (Validation set).
Who may be able to join
- Primary liver transplants from deceased donors
Who cannot join
- combined transplants (liver transplanted simultaneously with another organ transplant)
- living donor liver transplant
- domino liver transplant
- pediatric transplants
- HIV+ recipients
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Early Allograft Failure Simplified Estimation (EASE). A Novel Predictive Model for Estimating Early Allograft Failure in Liver Transplantation: a Multicenter Italian Study With a UK Validation Cohort.
A variety of clinical scores have been developed with the intent to predict early allograft failure after liver transplantation. With the present study the investigators aim to validate the recently published L-GrAFT Score on a multicenter cohort from 14 liver transplant centers in Italy.
Secondly, after identifying coefficients which are peculiar for the Italian transplant population, the investigators aim to develop a novel, simplified model for the estimation of early allograft failure (EASE Score).
Thirdly, the investigators plan to validate the EASE Score on a population from two liver transplant centers in the United Kingdom.
Read the detailed description
Liver transplantation (LT) is the gold standard treatment for end-stage liver disease. The broadening of indications has caused a growing gap between patients on the waiting list and those who receive a transplant with the consequence of patients still dying while awaiting to be transplanted.
This phenomenon has led the transplant community to expand the donors pool, thus including organs with a higher risk profile. The so called marginal organs carry a higher risk of failure especially in the early post-transplant phase. Early allograft failure (EAF) is known as a poor prognostic factor for patient survival.Treatment of graft failure is based on re-transplantation (Re-LT).
However, there are no clear-cut clinical/biochemical parameters to base the decision of Re-LT on. In addition, to which extent EAF is irreversible is not entirely predictable. Such prediction has been the objective of extensive research and debate as it can guide the physicians through the decision whether or not re-transplanting a recipient of a failing graft.
The availability of an easy algorithm to quickly identify the cases who are irreversibly heading towards graft failure and need re-LT is highly desirable.
Various definitions of EAF have been introduced but they all share the same limitation of being based on a dichotomous evaluation of biochemical parameters (e.g. AST, INR, bilirubin, etc. below or above a certain cut-off level).
Recently, a new score has been developed with the aim of overcoming this limitation: the Liver Graft Assessment Following Transplantation (L-GrAFT). This score not only provides a tool to diagnose EAF but also assesses the severity and the evolution of EAF using the kinetics of a set of biochemical parameters. However, L-GrAFT is predictive of EAF at 90 days, is based on 31 biochemical determinations and has not been validated in a multicenter setting.
With the present study the investigators aim:
- to evaluate the performance of the L-GrAFT score and its ability to predict graft loss in the early post-operative phase (i.e. 90 days after LT) in a cohort of patients who received a primary LT from 2016 to 2017 in one of 14 LT Centers based in Italy, analyzing their prospectively maintained databases with a minimum follow up of 6 months;
- to develop a simplified algorithm, derived from the L-GrAFT algorithm, based on the Italian LT population, reducing the number of determinations allowing an easier data entry, which is predictive of EAF at 90 (90dEASE Score) and also at 30 days post LT (30dEASE Score);
- to validate the EASE scores on a population internal to the Italian database, using bootstrap methodology;
- to validate the EASE scores on an external UK liver transplant Cohort. The investigators are planning to present the results of the study in international congresses and meetings and after that to produce a manuscript.
- Conditions
- Liver Transplant Failure
- Being tested
- Liver transplantation
- Keywords
- liver transplant, allograft failure, primary dysfunction, early outcome, survival analysis, primary non-function, retransplant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liver transplantationProcedure or surgery
Liver transplantation from deceased donors
| Study group | Role | What they receive |
|---|---|---|
| Training set | Cohort of consecutive liver transplants performed in 2016-2017 from 14 liver transplant centers in Italy Receives: Procedure: Liver transplantation | |
| Validation set | Cohort of consecutive liver transplants performed in 2016-2017 from 2 liver transplant centers in the United Kingdom Receives: Procedure: Liver transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Early Allograft Failure
Graft loss after liver transplantation
Measured: 90 days
Secondary outcomes (1)
Early Allograft Failure
Graft loss after liver transplantation
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2019
- Study start15 Jun 2018
- Primary completion28 Nov 2018
- Study completion10 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Liver Transplant FailureStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 2,350 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Azienda Ospedaliero, Universitaria Pisana, The Mediterranean Institute for Transplantation and Advanced Specialized Therapies, University Hospital Padova, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, A.O. Ospedale Papa Giovanni XXIII, Ospedali Riuniti Ancona, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Azienda Ospedaliero-Universitaria di Modena, University of Roma La Sapienza, Azienda Ospedaliera Universitaria Integrata Verona, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Azienda Ospedaliera Niguarda Cà Granda, A.O.U. Città della Salute e della Scienza, University Hospital Birmingham NHS Foundation Trust, Newcastle-upon-Tyne Hospitals NHS Trust
- Responsible party
- Principal investigator, Prof. Alfonso Avolio, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Investigators
- Alfonso W Avolio, MD, Principal investigator, alfonso.avolio@unicatt.it
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03858088
- Sponsor's protocol ID
- Prot. 35355/18 ID:2232
- Acronym
- EASE
- Status last verified
- Feb 2019
- First submitted
- 27 Feb 2019
- Last updated
- 1 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Agopian VG, Harlander-Locke MP, Markovic D, Dumronggittigule W, Xia V, Kaldas FM, Zarrinpar A, Yersiz H, Farmer DG, Hiatt JR, Busuttil RW. Evaluation of Early Allograft Function Using the Liver Graft Assessment Following Transplantation Risk Score Model. JAMA Surg. 2018 May 1;153(5):436-444. doi: 10.1001/jamasurg.2017.5040.
PubMed 29261831
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Allograft Failure Simplified Estimation (EASE). A Novel Predictive Model for Estimating Early Allograft Failure in Liver Transplantation: a Multicenter Italian Study With a UK Validation Cohort.
- ClinicalTrials.gov ID
- NCT03858088
- Acronym / sponsor ID
- EASE / Prot. 35355/18 ID:2232
- Conditions
- Liver Transplant Failure
- Keywords
- liver transplant, allograft failure, primary dysfunction, early outcome, survival analysis, primary non-function, retransplant
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 2,350 participants (actual)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Collaborators
- Azienda Ospedaliero, Universitaria Pisana, The Mediterranean Institute for Transplantation and Advanced Specialized Therapies, University Hospital Padova, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, A.O. Ospedale Papa Giovanni XXIII, Ospedali Riuniti Ancona, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Azienda Ospedaliero-Universitaria di Modena, University of Roma La Sapienza, Azienda Ospedaliera Universitaria Integrata Verona, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Azienda Ospedaliera Niguarda Cà Granda, A.O.U. Città della Salute e della Scienza, University Hospital Birmingham NHS Foundation Trust, Newcastle-upon-Tyne Hospitals NHS Trust
- Study start
- 15 Jun 2018 (actual)
- Primary completion
- 28 Nov 2018 (actual)
- Study completion
- 10 Jan 2019 (actual)
- First posted
- 28 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A variety of clinical scores have been developed with the intent to predict early allograft failure after liver transplantation. With the present study the investigators aim to validate the recently published L-GrAFT Score on a multicenter cohort from 14 liver transplant centers in Italy.
Secondly, after identifying coefficients which are peculiar for the Italian transplant population, the investigators aim to develop a novel, simplified model for the estimation of early allograft failure (EASE Score).
Thirdly, the investigators plan to validate the EASE Score on a population from two liver transplant centers in the United Kingdom.
Detailed description
Liver transplantation (LT) is the gold standard treatment for end-stage liver disease. The broadening of indications has caused a growing gap between patients on the waiting list and those who receive a transplant with the consequence of patients still dying while awaiting to be transplanted.
This phenomenon has led the transplant community to expand the donors pool, thus including organs with a higher risk profile. The so called marginal organs carry a higher risk of failure especially in the early post-transplant phase. Early allograft failure (EAF) is known as a poor prognostic factor for patient survival.Treatment of graft failure is based on re-transplantation (Re-LT).
However, there are no clear-cut clinical/biochemical parameters to base the decision of Re-LT on. In addition, to which extent EAF is irreversible is not entirely predictable. Such prediction has been the objective of extensive research and debate as it can guide the physicians through the decision whether or not re-transplanting a recipient of a failing graft.
The availability of an easy algorithm to quickly identify the cases who are irreversibly heading towards graft failure and need re-LT is highly desirable.
Various definitions of EAF have been introduced but they all share the same limitation of being based on a dichotomous evaluation of biochemical parameters (e.g. AST, INR, bilirubin, etc. below or above a certain cut-off level).
Recently, a new score has been developed with the aim of overcoming this limitation: the Liver Graft Assessment Following Transplantation (L-GrAFT). This score not only provides a tool to diagnose EAF but also assesses the severity and the evolution of EAF using the kinetics of a set of biochemical parameters. However, L-GrAFT is predictive of EAF at 90 days, is based on 31 biochemical determinations and has not been validated in a multicenter setting.
With the present study the investigators aim:
- to evaluate the performance of the L-GrAFT score and its ability to predict graft loss in the early post-operative phase (i.e. 90 days after LT) in a cohort of patients who received a primary LT from 2016 to 2017 in one of 14 LT Centers based in Italy, analyzing their prospectively maintained databases with a minimum follow up of 6 months;
- to develop a simplified algorithm, derived from the L-GrAFT algorithm, based on the Italian LT population, reducing the number of determinations allowing an easier data entry, which is predictive of EAF at 90 (90dEASE Score) and also at 30 days post LT (30dEASE Score);
- to validate the EASE scores on a population internal to the Italian database, using bootstrap methodology;
- to validate the EASE scores on an external UK liver transplant Cohort. The investigators are planning to present the results of the study in international congresses and meetings and after that to produce a manuscript.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Training set | – | Procedure: Liver transplantationCohort of consecutive liver transplants performed in 2016-2017 from 14 liver transplant centers in Italy |
| Validation set | – | Procedure: Liver transplantationCohort of consecutive liver transplants performed in 2016-2017 from 2 liver transplant centers in the United Kingdom |
Who may qualify
- Ages
- 18 to 73 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- A total of 1800 recipients of a primary liver transplant (LT) from 14 LT Centers from Italy (Training set) and 550 recipients of LT from 2 LT Centers from the United Kingdom (Validation set).
Key inclusion criteria (1 listed)
- Primary liver transplants from deceased donors
Key exclusion criteria (5 listed)
- combined transplants (liver transplanted simultaneously with another organ transplant)
- living donor liver transplant
- domino liver transplant
- pediatric transplants
- HIV+ recipients
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 |
|---|---|---|
| Liver transplantationLiver transplantation from deceased donors | Procedure or surgery | Training set, Validation set |
Primary outcome
Early Allograft Failure
Time frame: 90 days
Graft loss after liver transplantation
1 secondary outcome
Early Allograft Failure
Time frame: 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2019.
- Background: PubMed 29261831Agopian VG, Harlander-Locke MP, Markovic D, Dumronggittigule W, Xia V, Kaldas FM, Zarrinpar A, Yersiz H, Farmer DG, Hiatt JR, Busuttil RW. Evaluation of Early Allograft Function Using the Liver Graft Assessment Following Transplantation Risk Score Model. JAMA Surg. 2018 May 1;153(5):436-444. doi: 10.1001/jamasurg.2017.5040.
- Individual participant dataSharing planned: No
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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.
Alfonso W Avolio, MD principal investigator
alfonso.avolio@unicatt.it
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Liver Transplant Failure, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
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 1 inclusion and 5 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 1 Mar 2019. 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 Italy. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Early Allograft Failure (time frame: 90 days). 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 NCT03858088, which also lists 1 linked publication.
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 1 Mar 2019.