Prediction of Lung Transplant Outcome

NCT07356752 | Active Not Recruiting

• 2 other identifiers: 2023_0104ID RCB
• Study Type: interventional
• Target: 4,200
• Locations: 1 country
• Sites: 9

Brief Summary

Plain Language Summary of the PLUTO Study Prediction of Lung Transplant Outcomes (PLUTO) What is this study about? This study aims to improve how doctors predict the health of lung transplant recipients over time. Many people with severe lung disease need a transplant, but even after receiving a new lung, some still face serious health issues. One of the biggest problems is chronic lung transplant dysfunction (CLAD), which can slowly damage the new lung and is currently irreversible. What is the goal of the study? Researchers want to better understand why some people do worse after a lung transplant. Researchers hope to identify early warning signs and improve diagnosis. The main goal is to build a model that can predict how well a lung transplant will function over time, using routine health data and test results from transplant patients. Who can take part in this study? People aged 15 and older who had a lung transplant between 2009 and 2027 and are being followed at one of the study centers. People who speak French and have national health insurance. People who gave written consent (or whose guardians did, if under 18). The study may also use past data from deceased patients who did not object to research use. How will the study work? The study will follow about 4,200 lung transplant recipients across many centers in France. Researchers will collect clinical data, lung function tests, biopsy results, and blood samples. Researchers will also study new biomarkers (signals in the body that may show how well a transplant is doing) found in blood or lung samples. Using these data, the investigators will build and test tools to predict transplant outcomes. Why is this research important? By understanding early signs of transplant problems, doctors can act sooner and tailor treatment for each person. This may improve long-term survival after a lung transplant and help guide future research. How long is the study? Each participant will be followed for about 3 years, and the full study will last 6 years, including data analysis.

Conditions

Chronic Lung Allograft Dysfunction (CLAD); Chronic Rejection of Lung Transplant; Graft Dysfunction; Lung Transplantation

Keywords

lung, transplantation, graft, dysfunction, allograft, CLAD; lung; transplantation; lung transplantation; graft; dysfunction; graft dysfunction; allograft; chronic lung allograft dysfunction; CLAD; rejection; chronic rejection; biomarkers; lung function; risk factors; cohort; prognosis; FEV1

Outcome Measures

Primary Outcomes (1)

• Discrimination Performance of the Multidimensional Dynamic Prognostic Model for Lung Graft Outcomes, Measured by Area Under the Curve (AUC)

  To develop a multidimensional and dynamic prediction system for lung graft outcomes, joint multivariate Bayesian models with shared parameters and optimal artificial intelligence approaches will be used to assess associations between longitudinal biomarkers and survival data. This approach combines a Cox model linking time-to-event data with joint mixed models estimating trajectories of repeated measures. Clinical, biological, functional, histological and immunological variables before, during and after transplantation will be included in the Cox model, while repeated post-transplantation measures will be integrated into the mixed models. The effect of repeated measures will be evaluated using the last value, slope, and cumulative effect (area under the curve). The best model will be selected based on its discrimination performance, measured by Area Under the Curve (AUC), and evaluated in internal and external cohorts.

  72 months

Secondary Outcomes (4)

• Number of Distinct Graft Dysfunction Phenotypes Identified by Hierarchical Clustering Analysis

  72 months

• Differential Expression Levels of Candidate Biomarkers Between Patients With and Without Graft Dysfunction (Cross-Sectional Analysis)

  72 months

• Validation of Differential Expression of Candidate Biomarkers in an Independent External Cohort (Cross-Sectional Analysis)

  72 months

• Improvement in Discrimination Performance (AUC) of the Prognostic Model After Integration of Validated Biomarkers

  72 months

Study Arms (1)

patients who have been transplanted or retransplanted and who are followed-up

OTHER

Patients aged 15 and over transplanted (first or re transplantation, single, bilateral or combined) between 01/01/2009 and the date of the first prospective inclusion, benefiting from regular monitoring in one of the participating center. * Newly transplanted patient single, bilateral LTx, combined LTx) aged of 15 or more at the moment of transplantation, in one of the participating center between the date of the first prospective inclusion in during three years * Deceased patients before the beginning of the study, transplanted between 01/01/2009 and the date of the first prospective inclusion, who have not objected to the reuse of their health data.

Other: Research Blood Sampling and Biocollection

Interventions

Research Blood Sampling and Biocollection OTHER

Blood sampling and biocollection for research purposes, in addition to routine clinical care. Samples include plasma (EDTA tubes), peripheral blood mononuclear cells (CPT tubes), cell-free DNA (Streck tubes), PaxGene tubes and other predefined blood samples collected at clinically indicated time points according to the PLUTO study schedule. When transbronchial biopsies (TBB) are performed for clinical indications, additional tissue fragments are collected for the biocollection. Induced sputum and stool samples may also be collected. These samples are used for biomarker analyses and for the development and validation of multidimensional prognostic models of lung graft function and outcomes.

patients who have been transplanted or retransplanted and who are followed-up

Eligibility Criteria

• Age: 15 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients understanding the French language
• Having signed an informed consent form for this study\*, and for patients aged 15 to 18 that the holder(s) of parental authority has signed the informed consent
• Being covered by a national health insurance \* Already transplanted patient deceased before the beginning of the study: only clinical data (including biological samples clinically indicated likely to be reused, like serum of transbronchial biopsy (tbb)) will be included under condition of tracing any refusal, reluctance, reservations to the use of data, in patient files, by text analysis in all available digital documents. This approach allows both an exhaustive analysis in a timely, rapid way, that human reading would not allow. In case of mention of refusal, reluctance, reservations, the patient's data will not be collected.

You may not qualify if:

• Hemoglobin levels inferior than or equal to 8g/dl
• Patients not understanding the French language
• Don't being covered by a national health insurance
• Being under guardianship or curatorship
• Pregnant women\* \* Candidate for LTx are not allowed for pregnancy. During the follow up, pregnancies are permitted subject to medical approval of the project and close monitoring. It was decided that during pregnancy the participation for biocollection, would be suspended temporally. Realistically 1/ in the former situation patient candidate for Lung transplantation are not pregnant, 2/ in contrast long after transplantation, medically supervised pregnancy could occur. In that case, research sampling might be suspended temporarily.

Sponsors & Collaborators

• Hopital Foch: lead

Study Sites (9)

APHP - site de Cochin

Paris, Paris 14, 75014, France

Location

APHP - site de Bichat

Paris, Paris 18, 75018, France

Location

CHU Strasbourg

Strasbourg, Strasbourg, 67084, France

Location

CHU Bordeaux & INSERM U1045

Talence, Talence, 33404, France

Location

Chu Grenoble

Grenoble, 38700, France

Location

CML La Fondation Hôpital Saint-Joseph

Le Plessis-Robinson, 92350, France

Location

CHU LYON

Lyon, 69007, France

Location

CHU Nantes Hôpital Maison Blanche

Nantes, 44000, France

Location

Hôpital Foch

Suresnes, 92150, France

Location

MeSH Terms

Conditions

Rejection, Psychology

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Study Officials

• Antoine Roux, Pr

  Hopital Foch

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: ambispective, interventional study with minimal risks and constraints

Study Record Dates

• First Submitted: July 18, 2025
• First Posted: January 21, 2026
• Study Start: June 17, 2025
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): June 1, 2031
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (9)