Clinical trial NCT06125535: Biomolecular Phenotyping of Lung Transplant Recipients
Official title: Biomolecular Phenotyping of Lung Transplant Recipients: a Prospective Observational Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Lung Transplant Failure
Keywords: lung transplant
primary graft dysfunction
prospective observational study
biomarkers
Lead sponsor: Policlinico Hospital
Sponsor class: OTHER
Collaborators: name: University of Milan
First posted: 2023-11-09
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All the consecutive adult patients have undergone primary double LUTX at the promoting institution.

Brief 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.

Detailed 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).

Eligibility criteria: Inclusion Criteria:

* undergone double LUTX
* age \> 18 years old

Exclusion Criteria:

* single LUTX
* re-transplantation

Primary outcomes:
measure: Primary Graft Dysfunction
timeFrame: <= 72 hours from graft reperfusion
Secondary outcomes:
measure: 28-days organ support free-days
timeFrame: 28 days from ICU admission
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Fondazione IRCCS Ca'Granda - Ospedale Maggiore Policlinico
Study officials:
affiliation: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
name: Giacomo Grasselli, Porf
role: STUDY_DIRECTOR
affiliation: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
name: Vittorio Scaravilli, MD
role: PRINCIPAL_INVESTIGATOR
References: