Biomolecular Phenotyping of Lung Transplant Recipients

Lung Transplant Failure Clinical Trial

— LUTX_phenotype  

Official title:

Biomolecular Phenotyping of Lung Transplant Recipients: a Prospective Observational Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06125535
• Other study ID #: LUTX_phenotype
• Status: Recruiting
• Start date: January 1, 2022
• Est. completion date: March 31, 2024

Study information

• Verified date: November 2023
• Source: Policlinico Hospital
• Contact: Vittorio Scaravilli, MD
• Phone: 0255033275
• Email: vittorio.scaravilli[@]unimi.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Primary graft dysfunction (PGD) is a common problem after a lung transplant. It's a sudden lung injury that affects around 30% of patients within 72 hours of getting a new lung. PGD can vary in severity, from mild issues seen on X-rays to severe lung problems, and it can also affect other parts of the body, like the heart and kidneys.

The investigators believe that using precision medicine can identify different groups of patients with varying levels of inflammation and provide them with treatments tailored to their specific conditions. This approach has been successful in treating other serious conditions like acute respiratory distress syndrome (ARDS). Currently, researchers haven't classified lung transplant patients in this way, and there's limited information on early blood markers for PGD.

In an upcoming study, the investigators aim to group lung transplant patients based on their blood markers related to inflammation, blood clotting, and blood vessel problems. The investigators also want to see if these groups are linked to their overall outcomes, especially when it comes to PGD.

Description:

Primary graft dysfunction (PGD) is the most common complication after lung transplant (LUTX). PGD is an acute form of lung injury with an incidence of 30%, defined upon alteration of oxygenation and radiographic criteria occurring <72 hours after graft reperfusion.

The PGD definition does not consider the heterogeneity of clinical manifestations of ischemia-reperfusion (I/R) injury. First, PGD severity may vary from mild radiographic signs to life-threatening lung injury. Second, duration may differ: most patients manifest transient hypoxia, but a minority have persistent respiratory failure. Finally, PGD is associated with hemodynamic and renal failure, suggesting that it might be considered a heterogeneous syndrome characterized by multisystemic widespread endothelial barrier damage and inflammation activation due to I/R injury rather than an alteration of the sole lung function.

Following the new paradigm of precision medicine, the investigators hypothesize that predictive enrichment may allow for detecting different - and potentially treatable - traits (i.e., hypo vs. hyperinflammatory) of PGD and applying targeted treatments to sub-cohorts. As for other critical illnesses (i.e., acute respiratory distress syndrome - ARDS, sepsis), the investigators envision the possibility of carrying out biological subtyping of LUTX patients to select the patients with the lowest chance of harm for treatment. In the similar -but not equivalent- context of ARDS, it has been proven that treatments (e.g., positive end-expiratory pressure, fluid management, simvastatin) that disappointingly failed to benefit the overall patients' population provided benefit in specific patients' subcohorts. Biological phenotyping of LUTX recipients has never been carried out, and literature is ample but sparse regarding early PGD plasmatic biomarkers.

With this prospective observational study, the investigators aim to assess: 1/ whether LUTX recipients can be clustered based on early plasma concentration of biomarkers of inflammation, coagulation, and endothelial activation, and 2/ whether these clusters could be associated with clinical outcomes (and specifically PGD).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: March 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• undergone double LUTX

• age > 18 years old

Exclusion Criteria:

• single LUTX

• re-transplantation

• bridge-to-LUTX by extracorporeal membrane oxygenation

Related Conditions & MeSH terms

• Lung Transplant Failure

Intervention

Diagnostic Test:
• Sub-phenotyping by biomarkers concentration
Plasma will be collected at ICU admission (i.e., < 6 hours from graft reperfusion), centrifuged (1500G for 15 min), frozen at -80°c, and then centralized at the Institutional laboratory. The following biomarkers will be assessed: sRAGE, SP-D, P-selectin (for alveolar damage); ICAM-1, IL6, IL8, IL10, TNF-alfa, IFN-gamma, CCL2, GM-CSF, TNFR1 (inflammation); angiopoietin-1, angiopoietin-2, TIMP-1 (endothelial damage). Analyses will be carried out on a Luminex platform (BioRad, Hercules, California, USA) - available at our Institution.

Locations

Country	Name	City	State
Italy	Fondazione IRCCS Ca'Granda - Ospedale Maggiore Policlinico	Milan

Sponsors (1)

Lead Sponsor	Collaborator
Policlinico Hospital

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Graft Dysfunction	PGD incidence, defined and graded following the most recent ISHLT society guidelines, as hypoxia (i.e., PaO2/FiO2 < 300 mmHg) with bilateral lung infiltrates.	<= 72 hours from graft reperfusion
Secondary	28-days organ support free-days	Number of days at 28 days from ICU admission free from: - extracorporeal membrane oxygenation; - mechanical ventilation; - renal replacement therapy; - vasoactive support.	28 days from ICU admission