Ex Vivo Lung Perfusion in Bergamo Lung Transplant Program
Condition: Ex Vivo Lung Perfusion; Lung Transplantation
Study type: Observational [Patient Registry]

Summary: 
      Ex Vivo Lung Perfusion (EVLP) appears to be an effective strategy to expand the lung donor
      pool by better evaluation and reconditioning of non standard grafts. Today, EVLP is clinical
      practice at the most active transplant centers in North America and Europe.

      The aim of this observational prospective monocentric study is to prove the safety and
      efficacy of EVLP performed in the setting of Bergamo lung transplant program.

      A statistically estimated sample size would not fit with the small numbers of Italian lung
      transplant activity, so the investigators decided to enrol 10 consecutive recipients of
      grafts subjected to EVLP.

      Non standard grafts from Brain Dead Donors (BDD) and Donors after Cardiac Death (DCD) and
      standard grafts that will undergo prolonged cold ischemic time will be selected for EVLP.

      The donor lung procurement operation will be done in the usual manner. The EVLP procedure
      will be performed in the operating theater of Papa Giovanni XXIII Hospital. The investigators
      decided to adopt Toronto protocol since it involves some lung protective strategies. EVLP
      will proceed over a period of at least 4 and not more than 6 hours.

      After 60, 120, 180 and 240 minutes from the start of EVLP the following parameters will be
      evaluated:

        -  ratio of the partial pressure of arterial oxygen to fraction of inspired oxygen
           (PO2/FiO2, mmHg)

        -  Pulmonary Vascular Resistance (PVR, dine*s/cm5)

        -  Peak Inspiratory Pressure (PIP, cmH2O) and mean airways Pressure (Pawm, cmH2O)

        -  dynamic lung Compliance (Cpldyn, ml/ cmH2O)

        -  ΔPO2 = pulmonary vein PO2 - pulmonary artery PO2 (mmHg). Moreover, after 60 and 240
           minutes from the start of EVLP a graft X-ray and a bronchoscopy will be performed.

      The lung graft will be accepted for transplantation if, after 240 minutes from the start of
      EVLP, the following conditions are fulfilled:

        -  PO2/FiO2 >350 mmHg

        -  stability or reduction of PVR compared with the measurement at the baseline assessment
           time point

        -  stability or reduction of PIP and Pawm compared with the measurement at the baseline
           assessment time point

        -  stable or better Cpldyn compared with the measurement at the baseline assessment time
           point

        -  ΔPO2 >400 mmHg

        -  improvement of X-ray imaging compared with that at the baseline assessment time point

        -  exclusion of oedema and purulent secretions by bronchoscopy. After transplantation the
           recipients will be followed-up for 1 year according to a scheduled timetable.

      Data about the EVLP and transplant procedure and about the characteristics of donors and
      recipients will be collected in a dedicated electronic Case report form (eCRF) according to
      Good Clinical Practice.
    

Detailed description: 
      Ex Vivo Lung Perfusion (EVLP) has been allowing to expand the lung donor pool by better
      evaluation and reconditioning of non standard grafts. The results of both completed and still
      recruiting prospective clinical trials show similar short- and long-term post-transplant
      outcomes with non standard and standard grafts subjected to EVLP and traditionally preserved
      standard grafts. Today, EVLP is clinical practice at the most active transplant centers in
      North America and Europe.

      The aim of this observational prospective monocentric study is to prove the safety and
      efficacy of EVLP performed in the setting of Bergamo lung transplant program.

      A statistically estimated sample size would not fit with the small numbers of Italian lung
      transplant activity, so the investigators decided to enrol 10 consecutive recipients of
      grafts subjected to EVLP.

      Non standard grafts from Brain Dead Donors (BDD) and Donors after Cardiac Death (DCD) and
      standard grafts that will undergo prolonged cold ischemic time will be selected for EVLP.
      Grafts from donors over the age of 65 and/or with a smocking history of more than 10
      pack-year and/or with chronic lung disease and/or with gross gastric aspiration and/or with a
      diagnosis of established pneumonia will be rejected.

      The donor lung procurement operation will be done in the usual manner. After excision, the
      right and left graft will not be divided and will be packed in ice for transportation.

      The EVLP procedure will be performed in the operating theater of Papa Giovanni XXIII
      Hospital. The investigators decided to adopt Toronto protocol since it involves some lung
      protective strategies. EVLP will proceed over a period of at least 4 and not more than 6
      hours.

      After 60, 120, 180 and 240 minutes from the start of EVLP the following parameters will be
      evaluated:

        -  PO2/FiO2 (mmHg)

        -  Pulmonary Vascular Resistance (PVR, dine*s/cm5)

        -  Peak Inspiratory Pressure (PIP, cmH2O) and mean airways Pressure (Pawm, cmH2O)

        -  dynamic lung Compliance (Cpldyn, ml/ cmH2O)

        -  ΔPO2 = pulmonary vein PO2 - pulmonary artery PO2 (mmHg). Moreover, after 60 and 240
           minutes from the start of EVLP a graft X-ray and a bronchoscopy will be performed.

      The lung graft will be accepted for transplantation if, after 240 minutes from the start of
      EVLP, the following conditions are fulfilled:

        -  PO2/FiO2 >350 mmHg

        -  stability or reduction of PVR compared with the measurement at the baseline assessment
           time point

        -  stability or reduction of PIP and Pawm compared with the measurement at the baseline
           assessment time point

        -  stable or better Cpldyn compared with the measurement at the baseline assessment time
           point

        -  ΔPO2 >400 mmHg

        -  improvement of X-ray imaging compared with that at the baseline assessment time point

        -  exclusion of oedema and purulent secretions by bronchoscopy. If the lung graft is
           considered suitable for transplantation, the EVLP procedure will be stopped as described
           by Toronto protocol and the right and left graft will be divided and packed for
           hypothermic preservation until implantation.

      After transplantation the recipients will be followed-up for 1 year according to a scheduled
      timetable.

      Data about the EVLP and transplant procedure and about the characteristics of donors and
      recipients will be collected in a dedicated electronic Case Report Form (eCRF) according to
      Good Clinical Practice.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        All the patients on the waiting list for monolateral or bilateral lung transplantation at
        Bergamo lung transplant center