Developing Prediction Models for Allograft Failure After Liver Transplantation

NCT05289609 | Unknown

• 1 other identifier: 4571
• Study Type: observational
• Target: 5,000
• Locations: 11 countries
• Sites: 18

Brief Summary

Prompt identification of allograft failure (AF) is highly desirable to address patients to liver retransplantation, in order to maximize results and preserve patients safety. Recently, sophisticated kinetic models became available, offering the possibility to predict 90-day AF with unprecedented accuracy, by computing data from the first 10 days after liver transplant (LT). The growing utilization of extended criteria and cardiac death donors stimulates the transplant community to further refine such predictive models and validate them on a larger scale population of patients across the nations. This study aims to develop new algorithms for the timely prediction of AF at 90 and 365 days using a prospective international cohort from high-volume centers, to validate them on a large retrospective cohort, to identify the best time for retransplantation, to stratify the risk of AF according to the graft type (i.e. DBD, ECD, DCD, LD), to weigh the effect of risk-mitigation strategies, and to assess the correlation with post-LT morbidity and mortality.

Conditions

Liver Transplant Disorder

Keywords

Liver transplantation; Retransplantation; Allograft failure; End-stage liver disease; Graft loss; Patient survival; Ischemic cholangiopathy

Outcome Measures

Primary Outcomes (2)

• Allograft failure

  the irreversible loss of graft function leading to retransplantation or patient death

  within 90 days after liver transplantation

• Allograft failure

  the irreversible loss of graft function leading to retransplantation or patient death

  within 365 days after liver transplantation

Secondary Outcomes (3)

• Time to retransplantation

  365 days

• Complications after liver transplantation

  90 days

• Ischemic cholangiopathy

  365 days

Study Arms (2)

Prospective Cohort

Liver Transplant Recipients from High-volume centers (i.e., performing \>= 65 LTs per year)

Procedure: Liver Transplantation

Retrospective Cohort

Liver Transplant Recipients from Low-to-medium volume centers (i.e., performing \<65 LTs per year) and High-volume centers

Procedure: Liver Transplantation

Interventions

Liver Transplantation PROCEDURE

Individuals with end-stage liver disease will be subjected to liver transplantation from deceased or living donors

Prospective Cohort; Retrospective Cohort

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: based on self-representation of gender identity
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

5000 patients from 80 liver transplant centers (target size), divided in two cohorts: * Prospective: 2000 patients from 40 high-volume centers (performing ≥65 LT a year); 50 consecutive transplants; 365-day follow-up period. * Retrospective: 3000 patients from 40 medium-low volume centers (performing \<65 LT a year); data collection of LTs performed between 31/12/2019 and 1/1/2017; 75 cases per center. High-volume centers will be allowed to enroll patients in the retrospective cohort too, enrolling a total of 125 transplants (50 prospective and 75 retrospective ). Each cohort can accommodate \>40 centers without altering the balanced study design (once the 40-center target has been reached, each cohort can grow by a 20% extent above the target without altering the balance).

You may qualify if:

• Adult recipients (≥18 years)
• First transplant (retransplant cases should be enrolled if the first transplant is part of the study)
• DBD grafts
• DCD grafts (controlled and uncontrolled)
• DBD and DCD grafts managed by perfusion machines
• Living donor grafts (both left lobe and right lobe grafts) transplanted into adult recipients.
• Split liver grafts (both left lobe and right lobe grafts) transplanted into adult recipients.

You may not qualify if:

• Combined grafts (e.g., liver-kidney, liver-heart, liver-pancreas, multi-visceral grafts)
• Domino grafts
• Heterotopic grafts
• Double grafts
• Recipients undergoing liver transplants for cholangiocarcinoma and colorectal liver metastases

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead
• University of California, Los Angeles: collaborator
• University Hospital Padova: collaborator
• Mayo Clinic: collaborator
• Hospital Italiano de Buenos Aires: collaborator
• Tokyo Women's Medical University: collaborator
• Hospital Universitario La Paz: collaborator
• First Affiliated Hospital, Sun Yat-Sen University: collaborator
• University of Roma La Sapienza: collaborator
• University of Massachusetts, Worcester: collaborator
• The Cleveland Clinic: collaborator
• Dr. Rela Institute & Medical Centre: collaborator
• University of Toronto: collaborator
• Universidade Federal do Paraná: collaborator
• Royal Infirmary of Edinburgh: collaborator
• Erasmus Medical Center: collaborator

Study Sites (18)

Dumont-UCLA Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at UCLA

Los Angeles, California, 90095, United States

Location

Department of Transplant, Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

Division of Organ Transplantation, Department of Surgery, University of Massachusetts Memorial Hospital, University of Massachusetts

Worcester, Massachusetts, 01655, United States

Location

Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Division of Hepato Pancreatic Biliary Surgery and Liver Transplant Unit, Department of General Surgery, Hospital Italiano de Buenos Aires

Buenos Aires, C1199ABB, Argentina

Location

Liver Transplant Division, Santa Isabel Hospital

Blumenau, 89010-906, Brazil

Location

Multi-Organ Transplant and HPB Surgical Oncology, Division of General Surgery, University Health Network

Toronto, M5G 1L7, Canada

Location

First Affiliated Hospital, Sun Yat-Sen University

Guangzhou, 510060, China

Location

Dr Rela Institute and Medical Centre

Chennai, 600044, India

Location

Department of Surgery, Oncology and Gastroenterology, Padova University Hospital

Padua, 35122, Italy

Location

Department of Surgery, Oncology and Gastroenterology, Padova University Hospital

Padua, 35122, Italy

Location

General Surgery and Organ Transplantation Unit, Sapienza University of Rome

Roma, 00161, Italy

Location

Fondazione Policlinico Universitario A. Gemelli, IRCCS

Roma, 00168, Italy

Location

GSTeP - Gemelli Science and Technology Park, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168, Italy

Location

Department of Surgery, Tokyo Women's Medical University

Shinjuku-Ku, 162-8666, Japan

Location

Erasmus MC Transplant Institute, University Medical Center Rotterdam, Department of Surgery, Division of Hepato-Pancreato-Biliary and Transplant Surgery

Rotterdam, 3015 GD, Netherlands

Location

Cirugia General y del A. Digestivo, Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Department of Transplant Surgery, Edinburgh Transplant Centre, Royal Infirmary of Edinburgh

Edinburgh, EH16 4SA, United Kingdom

Location

Related Publications (16)

• 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.

  PMID: 29261831 BACKGROUND

• Agopian VG, Markovic D, Klintmalm GB, Saracino G, Chapman WC, Vachharajani N, Florman SS, Tabrizian P, Haydel B, Nasralla D, Friend PJ, Boteon YL, Ploeg R, Harlander-Locke MP, Xia V, DiNorcia J, Kaldas FM, Yersiz H, Farmer DG, Busuttil RW. Multicenter validation of the liver graft assessment following transplantation (L-GrAFT) score for assessment of early allograft dysfunction. J Hepatol. 2021 Apr;74(4):881-892. doi: 10.1016/j.jhep.2020.09.015. Epub 2020 Sep 23.

  PMID: 32976864 BACKGROUND

• Avolio AW, Franco A, Schlegel A, Lai Q, Meli S, Burra P, Patrono D, Ravaioli M, Bassi D, Ferla F, Pagano D, Violi P, Camagni S, Dondossola D, Montalti R, Alrawashdeh W, Vitale A, Teofili L, Spoletini G, Magistri P, Bongini M, Rossi M, Mazzaferro V, Di Benedetto F, Hammond J, Vivarelli M, Agnes S, Colledan M, Carraro A, Cescon M, De Carlis L, Caccamo L, Gruttadauria S, Muiesan P, Cillo U, Romagnoli R, De Simone P. Development and Validation of a Comprehensive Model to Estimate Early Allograft Failure Among Patients Requiring Early Liver Retransplant. JAMA Surg. 2020 Dec 1;155(12):e204095. doi: 10.1001/jamasurg.2020.4095. Epub 2020 Dec 16.

  PMID: 33112390 BACKGROUND

• Avolio AW, Lai Q, Cillo U, Romagnoli R, De Simone P. L-GrAFT and EASE scores in liver transplantation: Need for reciprocal external validation and comparison with other scores. J Hepatol. 2021 Sep;75(3):729-731. doi: 10.1016/j.jhep.2020.12.009. Epub 2020 Dec 17. No abstract available.

  PMID: 33340580 BACKGROUND

• Avolio AW, Contegiacomo A, Spoletini G, Moschetta G, Bianco G, Agnes S, Melcher ML, Burra P. Toward a novel evidence-based definition of early allograft failure in the perspective of liver retransplant. Transpl Int. 2021 Dec;34(12):2905-2907. doi: 10.1111/tri.14162. Epub 2021 Dec 6. No abstract available.

  PMID: 34784075 BACKGROUND

• Croome KP, Mathur AK, Aqel B, Yang L, Taner T, Heimbach JK, Rosen CB, Paz-Fumagalli R, Taner CB. Classification of Distinct Patterns of Ischemic Cholangiopathy Following DCD Liver Transplantation: Distinct Clinical Courses and Long-term Outcomes From a Multicenter Cohort. Transplantation. 2022 Jun 1;106(6):1206-1214. doi: 10.1097/TP.0000000000003928. Epub 2022 Aug 30.

  PMID: 34468429 BACKGROUND

• Chen S, Wang T, Luo T, He S, Huang C, Jia Z, Zhan L, Wang D, Zhu X, Guo Z, He X. Prediction of Graft Survival Post-liver Transplantation by L-GrAFT Risk Score Model, EASE Score, MEAF Scoring, and EAD. Front Surg. 2021 Nov 19;8:753056. doi: 10.3389/fsurg.2021.753056. eCollection 2021.

  PMID: 34869560 BACKGROUND

• Lai Q, Magistri P, Lionetti R, Avolio AW, Lenci I, Giannelli V, Pecchi A, Ferri F, Marrone G, Angelico M, Milana M, Schinnina V, Menozzi R, Di Martino M, Grieco A, Manzia TM, Tisone G, Agnes S, Rossi M, Di Benedetto F, Ettorre GM; Sarco-Model Study Group. Sarco-Model: A score to predict the dropout risk in the perspective of organ allocation in patients awaiting liver transplantation. Liver Int. 2021 Jul;41(7):1629-1640. doi: 10.1111/liv.14889. Epub 2021 Apr 22.

  PMID: 33793054 BACKGROUND

• Martins PN, Rizzari MD, Ghinolfi D, Jochmans I, Attia M, Jalan R, Friend PJ; ILTS Special Interest Group "DCD, Preservation and Machine Perfusion". Design, Analysis, and Pitfalls of Clinical Trials Using Ex Situ Liver Machine Perfusion: The International Liver Transplantation Society Consensus Guidelines. Transplantation. 2021 Apr 1;105(4):796-815. doi: 10.1097/TP.0000000000003573.

  PMID: 33760791 BACKGROUND

• Pareja E, Cortes M, Hervas D, Mir J, Valdivieso A, Castell JV, Lahoz A. A score model for the continuous grading of early allograft dysfunction severity. Liver Transpl. 2015 Jan;21(1):38-46. doi: 10.1002/lt.23990. Epub 2014 Nov 24.

  PMID: 25204890 BACKGROUND

• Olthoff KM, Kulik L, Samstein B, Kaminski M, Abecassis M, Emond J, Shaked A, Christie JD. Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl. 2010 Aug;16(8):943-9. doi: 10.1002/lt.22091.

  PMID: 20677285 BACKGROUND

• Patrono D, Cussa D, Sciannameo V, Montanari E, Panconesi R, Berchialla P, Lepore M, Gambella A, Rizza G, Catalano G, Mirabella S, Tandoi F, Lupo F, Balagna R, Salizzoni M, Romagnoli R. Outcome of liver transplantation with grafts from brain-dead donors treated with dual hypothermic oxygenated machine perfusion, with particular reference to elderly donors. Am J Transplant. 2022 May;22(5):1382-1395. doi: 10.1111/ajt.16996. Epub 2022 Feb 22.

  PMID: 35150050 BACKGROUND

• Petrowsky H, Rana A, Kaldas FM, Sharma A, Hong JC, Agopian VG, Durazo F, Honda H, Gornbein J, Wu V, Farmer DG, Hiatt JR, Busuttil RW. Liver transplantation in highest acuity recipients: identifying factors to avoid futility. Ann Surg. 2014 Jun;259(6):1186-94. doi: 10.1097/SLA.0000000000000265.

  PMID: 24263317 BACKGROUND

• Schlegel A, van Reeven M, Croome K, Parente A, Dolcet A, Widmer J, Meurisse N, De Carlis R, Hessheimer A, Jochmans I, Mueller M, van Leeuwen OB, Nair A, Tomiyama K, Sherif A, Elsharif M, Kron P, van der Helm D, Borja-Cacho D, Bohorquez H, Germanova D, Dondossola D, Olivieri T, Camagni S, Gorgen A, Patrono D, Cescon M, Croome S, Panconesi R, Carvalho MF, Ravaioli M, Caicedo JC, Loss G, Lucidi V, Sapisochin G, Romagnoli R, Jassem W, Colledan M, De Carlis L, Rossi G, Di Benedetto F, Miller CM, van Hoek B, Attia M, Lodge P, Hernandez-Alejandro R, Detry O, Quintini C, Oniscu GC, Fondevila C, Malago M, Pirenne J, IJzermans JNM, Porte RJ, Dutkowski P, Taner CB, Heaton N, Clavien PA, Polak WG, Muiesan P; DCD Collaborator Group. A multicentre outcome analysis to define global benchmarks for donation after circulatory death liver transplantation. J Hepatol. 2022 Feb;76(2):371-382. doi: 10.1016/j.jhep.2021.10.004. Epub 2021 Oct 14.

  PMID: 34655663 BACKGROUND

• Spoletini G, Ferri F, Mauro A, Mennini G, Bianco G, Cardinale V, Agnes S, Rossi M, Avolio AW, Lai Q. CONUT Score Predicts Early Morbidity After Liver Transplantation: A Collaborative Study. Front Nutr. 2022 Jan 7;8:793885. doi: 10.3389/fnut.2021.793885. eCollection 2021.

  PMID: 35071299 BACKGROUND

• Aby ES, Lee E, Saggi SS, Viramontes MR, Grotts JF, Agopian VG, Busuttil RW, Saab S. Pretransplant Sarcopenia in Patients With NASH Cirrhosis Does Not Impact Rehospitalization or Mortality. J Clin Gastroenterol. 2019 Oct;53(9):680-685. doi: 10.1097/MCG.0000000000001109.

  PMID: 30180152 BACKGROUND

MeSH Terms

Conditions

End Stage Liver Disease

Interventions

Liver Transplantation

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Digestive System Surgical Procedures; Surgical Procedures, Operative; Organ Transplantation; Transplantation

Study Officials

• Vatche Agopian

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

• Alfonso W Avolio

  Fondazione Policlinico universitario Agostino Gemelli IRCCS, Rome, Italy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alfonso W Avolio

CONTACT

00390630151; alfonso.avolio@policlinicogemelli.it

Gabriele Spoletini

CONTACT

00390630154955; gabriele.spoletini@policlinicogemelli.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 11, 2022
• First Posted: March 21, 2022
• Study Start: April 1, 2022
• Primary Completion: December 1, 2023
• Study Completion: April 1, 2024
• Last Updated: March 21, 2022

Record last verified: 2022-03

Locations

AR (1); GB (1); NL (1); US (4); CN (1); IT (5); CA (1); IN (1); BR (1); JP (1); ES (1)