Use of Machine-learning Algorithms, Biomarkers and Measures of Quality of Life to Personalize Medical Management of Liver and Heart Transplant Recipients (DARE)

This is an observational, low risk tissue based, non-pharmacological, retrospective-prospective study for adults heart and liver transplant patients, related to IRCCS Azienda Ospedaliero-Universitaria di Bologna (IRCCS AOUBO).

This clinical study is part of the national multicentric project DARE. The project has the wide overarching aim to develop digital solutions for personalized healthcare.

Study Overview

• Status: Not yet recruiting
• Conditions: Liver Transplantation; Hepatocellular Carcinoma (HCC); Heart Transplantation; Machine Learning; Major Cardiovascular Event; Artificial Intelligence (AI)

Detailed Description

This study is structured in two phases: 1) a retrospective phase that aims to develop ML-based scores that can allow to predict at patient level the risk of infections, cardiovascular diseases, new onset malignancies and chronic graft dysfunction, and describing the trajectory of this risk over time; 2) a prospective phase in which we test the association of biomarkers, QoL and frailty assessments with the ML-scores applied prospectively in heart and liver transplant recipients.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Luciano Potena, MD; Phone Number: 0512143725; Email: scompenso.trapiantocuore@aosp.bo.it

Study Locations

• Italy
  • Bologna, Italy, 40138
    • IRCCS - Azienda Ospedaliero-Universitaria di Bologna
    • Contact: Maria Cristina Morelli, MD; Phone Number: 0512144248; Email: mariacristina.morelli@aosp.bo.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

In the retrospective phase we will include all patients receiving heart or liver transplantation between January 2008 and December 2020 and surviving at least 6 months after surgery.

In the prospective phase we will consider for enrolment all patients with heart or liver transplantation actively on follow-up at IRCCS AOUBO from January 2024 and January 2026.

Description

Retrospective cohort Inclusion criteria Receiving a heart or liver transplantation at IRCCS AOUBO between January 2008 and December 2020.

Surviving at least 6 months after surgery Receiving at least one outpatient clinical assessment, comprising clinical evaluation, standard laboratory tests, and graft ultrasound Older than 18 years old

Exclusion criteria Unavailability of medical records in the standard data repositories of IRCCS AOUBO

Prospective cohort

Inclusion criteria Older thant 18 years old Receiving a heart or liver transplantation at least 6 months before study entry and being in active follow up at IRCCS AOUBO Obtaining informed consent

Exclusion criteria None

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infection	Infection, defined as systemic or organ-specific syndrome characterized by evidence of inflammatory response, abnormal organ function, and need for intravenous antimicrobial treatment, with or without microbiological isolate.	4 years
Major Cardiovascular Event (MACE)	Major Cardiovascular Event (MACE) defined as, fatal or non-fatal myocardial infarction, ischemic or hemorrhagic stroke, admission for heart failure, new onset arrhythmia, new onset symptoms for peripheral artery diseases	4 years
New onset malignancy	New onset malignancy, defined as hematopoietic or solid malignant neoplasm, developing after transplantation	4 years
Chronic graft dysfunction	Chronic graft dysfunction; in HTX recipients defined as onset of one or more of the following: CAV grade 2 or greater as diagnosed by standard of care coronary angiography; diffuse fibrosis with signs of diastolic or systolic left ventricle dysfunction. In LTX we define chronic graft dysfunction as progressive fibrosis, cholestasis and reduced protein synthesis, portal hypertension.	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ML-Scores as Surrogate Endpoints	The ML-scores developed to predict the primary outcomes will be used as secondary study outcomes for the prospective phase of the study, and will be tested as surrogate endpoints for clinical outcomes. In this approach, we will analyze the association between such defined surrogate endpoints and biomarkers, QoL and cognitive scores, and frailty measurements.	4 years

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Investigators: Principal Investigator: Luciano Potena, MD, IRCCS Azienda Ospedaliero-Universitaria di Bologna

Study record dates

Study Major Dates

• Study Start (Estimated): January 30, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: January 9, 2025
• First Submitted That Met QC Criteria: January 9, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 9, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: DARE; PNC0000002 3000435 (Other Grant/Funding Number: Bando PNRR - Ministero della Salute)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No