Clinical trial NCT06159933: Primary Graft Dysfunction, Pronation, Bilateral Lung Transplants
Official title: Early Prone Positioning as a Rescue Therapy for Severe Primary Graft Dysfunction After Bilateral Lung Transplant.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Lung Transplant
Primary Graft Dysfunction
Keywords: pronation, end-stage lung disease
Lead sponsor: University of Padova
Sponsor class: OTHER
First posted: 2023-12-07
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Historic cohort enrolled between January 2020 and December 2021; Prospective enrollment from January 2022 to April 2023. According to our local protocol, until December 2021, all patients developing PGD \>1 after LT were monitored in supine position for at least 24 hours, aiming at optimizing mechanical ventilation settings and right ventricular function, before considering PP. Only in case of radiological worsening or reduction in PaO2/FiO2 ratio patients were turned prone, generally between 24 and 48 hours after the diagnosis ('late PP' group), otherwise they were maintained supine ('supine' group). On the contrary, starting from January 2022 our local protocol was updated and all LT recipients developing PGD \>1 were routinely turned prone within 24 hours after the diagnosis ('early PP').Patients were placed in PP for at least 16 hours before being turned back to the supine position when meeting predefined criteria previously published by Guèrin et al.
Primary purpose: SUPPORTIVE_CARE

Brief summary: Proning manoeuvre as an early treatment for acute severe hypoxic respiratory failure has been implemented recently during the COVID-19 pandemic. This method was proposed more than fifty years ago to improve gas exchange : Proning Severe ARDS (PROSEVA) trial, however, was the milestone which demonstrated mortality benefit in patients with severe ARDS. Nevertheless, few analysis were performed on the effects of the prone position after lung transplantion (LT). The aim of the study is therefore to relate LT primary graft dysfunction (PGD) pathophysiology, which occurs in postoperative setting, to prone-positioning effects on ventilation-perfusion matching, improved lung compliance and clinical outcomes of impairedorgan patients.

Detailed description: Lung transplant is the final stage of intervention in dramatic respiratory failure unresponsive to other medical or surgical treatments: reduced disability, improved life quality and extended life are outweighed by still high mortality and morbidity of LT, compared to other solid organs transplants. LT patient survival is undermined, above all, by PGD onset up to 72h in postoperative scenario. Acute lung injury, characterized by reperfusion and ischemia damage, evolves in pulmonary edema and severely inflammed graft status. Tipical radiological findings are bilateral spreading infiltrates, whose treatment was until some years ago mainly supportive, i.e. protective mechanical ventilation and fluid restriction. Two retrospective studies recently demonstrated favorable oxygenation response in terms of PaO2/fraction-of-inspired-oxygen (FiO2) ratio and lung compliance. Our purpose was to broaden gas-exchange results by the analysis of short-term outcomes (i.e duration of mechanical ventilation, reintubation or tracheostomy, anastomotical complications, organ rejection in 30 days, acute kindney injury development and/or filtration necessity, hospital length and mortality). Our aim is to assess through this pilot study if early pronation (realized within 24 hours from admission) has a more favorable outcome on patients developing moderate/severe PGD within the first 24 postoperative hours.

Eligibility criteria: Inclusion Criteria:

* Age \> 18 y.o.
* First bilateral lung transplant
* PGD grade 2 or 3 within 24 hours from ICU admission Admission to ICU for post-operative monitoring after LTx
* Written informed consent obtained

Exclusion Criteria:

* Age \< 18 years old
* PGD\<2
* Single transplant
* Re-transplant
* IMV, venous-venous (V-V) or venous-arterial (V-A) extracorporeal membrane oxygenation (ECMO) before surgery
* Contraindications to prone positioning
* Refusal of consent

Primary outcomes:
measure: 28-day ventilator free days
timeFrame: From ICU admission up to 28 post-operative days (POD)
Secondary outcomes:
measure: Invasive mechanical ventilation (IMV)
timeFrame: From ICU adminission up to liberation from invasive mechanical ventilation
measure: Blood gas exchanges (PaO2 /FiO2 PaCo2, pH)
timeFrame: Within 24hours from ICU admission, at 72 hours later, in supine and prone position
Other outcomes:
Locations:
city: Padova
country: Italy
facility: Azienda Ospedaliera Università Padova
Study officials:
References: