<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03031067</url>
  </required_header>
  <id_info>
    <org_study_id>PIO-700</org_study_id>
    <secondary_id>159/2015/O/Disp</secondary_id>
    <nct_id>NCT03031067</nct_id>
  </id_info>
  <brief_title>Hypothermic Oxygenated Perfusion Versus Static Cold Storage for Marginal Graft</brief_title>
  <acronym>PIO</acronym>
  <official_title>Comparison Between Hypothermic Oxygenated Perfusion and Static Cold Storage of Organ From Extended Criteria Donors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Matteo Ravaioli</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Bologna</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      One of the major challenge in the field of organ transplantation is the shortage of donor&#xD;
      organs. Many patients waiting for organ transplantation die during the waiting time and many&#xD;
      patients wait for organ transplantation many years with a detrimental effect on their quality&#xD;
      of life, and increasing morbidity and the costs related to. Effective strategies, which&#xD;
      safely extends the donor pool, are therefore advocated. During the last 20 years the two main&#xD;
      policies to gain this purpose were the living donation and the utilization of extended&#xD;
      donor's criteria (ECD). These donors are supposed to yield a lower outcome than the&#xD;
      conventional donors and many research protocols were developed to reduce the preservation&#xD;
      injury (PI) and PI-related complications. Static cold storage (SCS) has been the standard&#xD;
      technique in clinical practice for liver and kidney preservation using particular solutions&#xD;
      (Wisconsin, Custodiol and Celsior) able to prevent cellular swelling. Recently, graft&#xD;
      preservation with hypothermic machine perfusion (HMP) is developing, because it seems to&#xD;
      improve early graft function due to increased tissue ATP concentrations upon reperfusion and&#xD;
      due to the continual flush of the microcirculation which removes waste products.&#xD;
&#xD;
      The addition of oxygen during the perfusion represents an innovation in the methods of&#xD;
      preservation in approved clinical setting seems to add further improvements of the graft. The&#xD;
      present study was designed in order to assess the impact of hypothermic oxygenated perfusion&#xD;
      (PIO) of marginal human kidney and liver compared with SCS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Our national single-center study, interventional with medical device, exploratory and safety,&#xD;
      will be assessed the optimal graft preservation, liver and kidney, from marginal donors ECD&#xD;
      (Expanded Criteria Donors), using hypothermic oxygenated perfusion (PIO) compared to the&#xD;
      static cold storage that is the preservation control method of custom. PIO will be applied to&#xD;
      10 ECD liver transplants and 10 ECD kidney transplants that meet the inclusion criteria.&#xD;
&#xD;
      The marginal graft will be perfused with oxygenated solution of preservation at 4°C for two&#xD;
      hours with Exiper, Bologna Machine Perfusion, developed by Medica s.p.a and our research&#xD;
      group.&#xD;
&#xD;
      Flow and pressure values will be set up for the kidney and liver perfusion, otherwise. The&#xD;
      oxygenation of solution will be performed by an oxygenator and a filter for decapneization /&#xD;
      oxygenation. During the perfusion the oxygen pressure will be required between 600-750 mmHg&#xD;
      (pO2 80-100 Kpa), as reported in the scientific literature. The pH, lactate concentration,&#xD;
      and oxygen (PO2) and carbon dioxide (PCO2) partial pressure were measured in the preservation&#xD;
      solution at T0 and T1 by means of a standard haemogasanalyzer.&#xD;
&#xD;
      After transplantation, the recipients will be monitored clinically to assess the graft&#xD;
      function. The liver's data will be compared with similar case treated with SCS in our centre&#xD;
      of transplant, retrospectively; instead, the kidney's data will be compared with the &quot;twin&quot;&#xD;
      organ transplanted without PIO, prospectively.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2016</start_date>
  <completion_date type="Actual">February 2018</completion_date>
  <primary_completion_date type="Actual">December 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>A matched-case analysis was developed: 10 HOPE-ECD livers and kidneys, HOPE-L and -K groups, were matched 1:3 with livers and kidneys preserved with static cold storage (SCS), SCS-L and -K groups respectively.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Graft function</measure>
    <time_frame>3 months post-transplantation (+18/-2 months)</time_frame>
    <description>Physiological values of serum creatinine and diuresis for kidney transplantation and bilirubin, AST, ALT, INR for liver transplantation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Graft survival - Kidney</measure>
    <time_frame>3 months post-transplantation (+18/-2 months)</time_frame>
    <description>Time (days) of graft survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Graft survival - Liver</measure>
    <time_frame>3 months post-transplantation (+18/-2 months)</time_frame>
    <description>Time (days) of graft survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient survival (kidney recipient)</measure>
    <time_frame>3 months post-transplantation (+18/-2 months)</time_frame>
    <description>Time (days) of patient survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient survival (liver recipient)</measure>
    <time_frame>3 months post-transplantation (+18/-2 months)</time_frame>
    <description>Time (days) of patient survival</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Liver Diseases</condition>
  <condition>Kidney Diseases</condition>
  <arm_group>
    <arm_group_label>Machine perfusion - Kidney</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The marginal kidney will be perfused with oxygenated solution of preservation at 4°C for two hours with Exiper, Bologna Machine Perfusion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Static cold storage - Kidney</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>The marginal kidney that was stored to cold (SCS), previously.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Machine perfusion - Liver</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The marginal liver will be perfused with oxygenated solution of preservation at 4°C for two hours with Exiper, Bologna Machine Perfusion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Static cold storage - Liver</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>The marginal liver that was stored to cold (SCS), previously.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Machine perfusion</intervention_name>
    <description>The graft preservation will be performed perfusing with a oxygenated solution of preservation at 4°C for two hours with Exiper, Bologna Machine Perfusion, developed by Medica s.p.a and our research group.&#xD;
Flow and pressure values will be set up for the kidney and liver perfusion, differently. The oxygenation of solution will be performed by an oxygenator and a filter for decapneization / oxygenation. During the perfusion the oxygen pressure will be required between 600-750 mmHg (pO2 80-100 Kpa), as reported in the scientific literature. The pH, lactate concentration, and oxygen (PO2) and carbon dioxide (PCO2) partial pressure were measured in the preservation solution at T0 and T1 by means of a standard haemogasanalyzer.</description>
    <arm_group_label>Machine perfusion - Kidney</arm_group_label>
    <arm_group_label>Machine perfusion - Liver</arm_group_label>
    <other_name>Hypothermic Oxygenated Perfusion</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Kidney donor: ECD.&#xD;
&#xD;
          -  Kidney recipient: single or dual kidney transplant recipients at our center, provided&#xD;
             consent.&#xD;
&#xD;
          -  Liver donor: ECD&#xD;
&#xD;
          -  Liver recipient: liver transplant recipients at our center, provided consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Kidney donor: no ECD, donor with vascular anatomical abnormalities and/or urinary&#xD;
             tract, donor with a risk infection, to increase cold ischemia time can not be avoided.&#xD;
&#xD;
          -  Kidney recipient: patients with severe atherosclerotic vascular disease, pathologies&#xD;
             predisposing to the onset of intra-operative surgical complications, such as&#xD;
             thrombophilia and hemophilia, antigenic incompatibility with donor determining the&#xD;
             acute rejection of the organ; patients waiting for kidney transplant pre-emptive,&#xD;
             multi-organ transplant, retransplantation.&#xD;
&#xD;
          -  Liver donor: no ECD, donor with vascular anatomical abnormalities, donor with a risk&#xD;
             infection, to increase cold ischemia time can not be avoided.&#xD;
&#xD;
          -  Liver recipient: patients with acute liver disease and with vascular abnormalities&#xD;
             and/or biliary tract requiring non-conventional reconstructive techniques, patients&#xD;
             waiting for multi-organ transplant, retransplantation, urgency transplant ( or with&#xD;
             MELD&gt;30).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Matteo Ravaioli, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Bologna S. Orsola-Malpighi Hospital, Transplantation and General Surgery Unit</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Antonio Daniele Pinna, Professor</last_name>
    <role>Study Director</role>
    <affiliation>University of Bologna S. Orsola-Malpighi Hospital, Transplantation and General Surgery Unit</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Azienda Ospedaliera di Bologna - Policlinico S. Orsola Malpighi</name>
      <address>
        <city>Bologna</city>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>O'Callaghan JM, Morgan RD, Knight SR, Morris PJ. Systematic review and meta-analysis of hypothermic machine perfusion versus static cold storage of kidney allografts on transplant outcomes. Br J Surg. 2013 Jul;100(8):991-1001. doi: 10.1002/bjs.9169.</citation>
    <PMID>23754643</PMID>
  </reference>
  <reference>
    <citation>Thuillier R, Allain G, Celhay O, Hebrard W, Barrou B, Badet L, Leuvenink H, Hauet T. Benefits of active oxygenation during hypothermic machine perfusion of kidneys in a preclinical model of deceased after cardiac death donors. J Surg Res. 2013 Oct;184(2):1174-81. doi: 10.1016/j.jss.2013.04.071. Epub 2013 May 21.</citation>
    <PMID>23731682</PMID>
  </reference>
  <reference>
    <citation>Hosgood SA, Nicholson HF, Nicholson ML. Oxygenated kidney preservation techniques. Transplantation. 2012 Mar 15;93(5):455-9. doi: 10.1097/TP.0b013e3182412b34.</citation>
    <PMID>22217529</PMID>
  </reference>
  <reference>
    <citation>Dutkowski P, Polak WG, Muiesan P, Schlegel A, Verhoeven CJ, Scalera I, DeOliveira ML, Kron P, Clavien PA. First Comparison of Hypothermic Oxygenated PErfusion Versus Static Cold Storage of Human Donation After Cardiac Death Liver Transplants: An International-matched Case Analysis. Ann Surg. 2015 Nov;262(5):764-70; discussion 770-1. doi: 10.1097/SLA.0000000000001473.</citation>
    <PMID>26583664</PMID>
  </reference>
  <verification_date>February 2018</verification_date>
  <study_first_submitted>January 19, 2017</study_first_submitted>
  <study_first_submitted_qc>January 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 25, 2017</study_first_posted>
  <last_update_submitted>February 12, 2018</last_update_submitted>
  <last_update_submitted_qc>February 12, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 13, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Bologna</investigator_affiliation>
    <investigator_full_name>Matteo Ravaioli</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Donors and donation</keyword>
  <keyword>Extended criteria donor</keyword>
  <keyword>Organ perfusion and preservation</keyword>
  <keyword>Liver transplantation</keyword>
  <keyword>Kidney transplantation</keyword>
  <keyword>Preservation injury</keyword>
  <keyword>Ischemia reperfusion injury</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
    <mesh_term>Kidney Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Individual participant data will be performed by application of a single code.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03031067
org study id: PIO-700
secondary id: 159/2015/O/Disp
nct id: NCT03031067
lead sponsor: 
has dmc: Yes
One of the major challenge in the field of organ transplantation is the shortage of donor
      organs. Many patients waiting for organ transplantation die during the waiting time and many
      patients wait for organ transplantation many years with a detrimental effect on their quality
      of life, and increasing morbidity and the costs related to. Effective strategies, which
      safely extends the donor pool, are therefore advocated. During the last 20 years the two main
      policies to gain this purpose were the living donation and the utilization of extended
      donor's criteria (ECD). These donors are supposed to yield a lower outcome than the
      conventional donors and many research protocols were developed to reduce the preservation
      injury (PI) and PI-related complications. Static cold storage (SCS) has been the standard
      technique in clinical practice for liver and kidney preservation using particular solutions
      (Wisconsin, Custodiol and Celsior) able to prevent cellular swelling. Recently, graft
      preservation with hypothermic machine perfusion (HMP) is developing, because it seems to
      improve early graft function due to increased tissue ATP concentrations upon reperfusion and
      due to the continual flush of the microcirculation which removes waste products.

      The addition of oxygen during the perfusion represents an innovation in the methods of
      preservation in approved clinical setting seems to add further improvements of the graft. The
      present study was designed in order to assess the impact of hypothermic oxygenated perfusion
      (PIO) of marginal human kidney and liver compared with SCS.
Our national single-center study, interventional with medical device, exploratory and safety,
      will be assessed the optimal graft preservation, liver and kidney, from marginal donors ECD
      (Expanded Criteria Donors), using hypothermic oxygenated perfusion (PIO) compared to the
      static cold storage that is the preservation control method of custom. PIO will be applied to
      10 ECD liver transplants and 10 ECD kidney transplants that meet the inclusion criteria.

      The marginal graft will be perfused with oxygenated solution of preservation at 4°C for two
      hours with Exiper, Bologna Machine Perfusion, developed by Medica s.p.a and our research
      group.

      Flow and pressure values will be set up for the kidney and liver perfusion, otherwise. The
      oxygenation of solution will be performed by an oxygenator and a filter for decapneization /
      oxygenation. During the perfusion the oxygen pressure will be required between 600-750 mmHg
      (pO2 80-100 Kpa), as reported in the scientific literature. The pH, lactate concentration,
      and oxygen (PO2) and carbon dioxide (PCO2) partial pressure were measured in the preservation
      solution at T0 and T1 by means of a standard haemogasanalyzer.

      After transplantation, the recipients will be monitored clinically to assess the graft
      function. The liver's data will be compared with similar case treated with SCS in our centre
      of transplant, retrospectively; instead, the kidney's data will be compared with the "twin"
      organ transplanted without PIO, prospectively.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: A matched-case analysis was developed: 10 HOPE-ECD livers and kidneys, HOPE-L and -K groups, were matched 1:3 with livers and kidneys preserved with static cold storage (SCS), SCS-L and -K groups respectively.
primary purpose: Treatment
masking: None (Open Label)
measure: Graft function
time frame: 3 months post-transplantation (+18/-2 months)
description: Physiological values of serum creatinine and diuresis for kidney transplantation and bilirubin, AST, ALT, INR for liver transplantation
measure: Graft survival - Kidney
time frame: 3 months post-transplantation (+18/-2 months)
description: Time (days) of graft survival
measure: Graft survival - Liver
time frame: 3 months post-transplantation (+18/-2 months)
description: Time (days) of graft survival
measure: Patient survival (kidney recipient)
time frame: 3 months post-transplantation (+18/-2 months)
description: Time (days) of patient survival
measure: Patient survival (liver recipient)
time frame: 3 months post-transplantation (+18/-2 months)
description: Time (days) of patient survival
arm group label: Machine perfusion - Kidney
arm group type: Experimental
description: The marginal kidney will be perfused with oxygenated solution of preservation at 4°C for two hours with Exiper, Bologna Machine Perfusion.
arm group label: Static cold storage - Kidney
arm group type: No Intervention
description: The marginal kidney that was stored to cold (SCS), previously.
arm group label: Machine perfusion - Liver
arm group type: Experimental
description: The marginal liver will be perfused with oxygenated solution of preservation at 4°C for two hours with Exiper, Bologna Machine Perfusion.
arm group label: Static cold storage - Liver
arm group type: No Intervention
description: The marginal liver that was stored to cold (SCS), previously.
intervention type: Device
intervention name: Machine perfusion
description: The graft preservation will be performed perfusing with a oxygenated solution of preservation at 4°C for two hours with Exiper, Bologna Machine Perfusion, developed by Medica s.p.a and our research group.
Flow and pressure values will be set up for the kidney and liver perfusion, differently. The oxygenation of solution will be performed by an oxygenator and a filter for decapneization / oxygenation. During the perfusion the oxygen pressure will be required between 600-750 mmHg (pO2 80-100 Kpa), as reported in the scientific literature. The pH, lactate concentration, and oxygen (PO2) and carbon dioxide (PCO2) partial pressure were measured in the preservation solution at T0 and T1 by means of a standard haemogasanalyzer.
arm group label: Machine perfusion - Kidney
arm group label: Machine perfusion - Liver
other name: Hypothermic Oxygenated Perfusion
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Matteo Ravaioli, PhD
role: Principal Investigator
affiliation: University of Bologna S. Orsola-Malpighi Hospital, Transplantation and General Surgery Unit
last name: Antonio Daniele Pinna, Professor
role: Study Director
affiliation: University of Bologna S. Orsola-Malpighi Hospital, Transplantation and General Surgery Unit
facility: 
country: Italy
citation: O'Callaghan JM, Morgan RD, Knight SR, Morris PJ. Systematic review and meta-analysis of hypothermic machine perfusion versus static cold storage of kidney allografts on transplant outcomes. Br J Surg. 2013 Jul;100(8):991-1001. doi: 10.1002/bjs.9169.
PMID: 23754643
citation: Thuillier R, Allain G, Celhay O, Hebrard W, Barrou B, Badet L, Leuvenink H, Hauet T. Benefits of active oxygenation during hypothermic machine perfusion of kidneys in a preclinical model of deceased after cardiac death donors. J Surg Res. 2013 Oct;184(2):1174-81. doi: 10.1016/j.jss.2013.04.071. Epub 2013 May 21.
PMID: 23731682
citation: Hosgood SA, Nicholson HF, Nicholson ML. Oxygenated kidney preservation techniques. Transplantation. 2012 Mar 15;93(5):455-9. doi: 10.1097/TP.0b013e3182412b34.
PMID: 22217529
citation: Dutkowski P, Polak WG, Muiesan P, Schlegel A, Verhoeven CJ, Scalera I, DeOliveira ML, Kron P, Clavien PA. First Comparison of Hypothermic Oxygenated PErfusion Versus Static Cold Storage of Human Donation After Cardiac Death Liver Transplants: An International-matched Case Analysis. Ann Surg. 2015 Nov;262(5):764-70; discussion 770-1. doi: 10.1097/SLA.0000000000001473.
PMID: 26583664
responsible party type: Sponsor-Investigator
investigator affiliation: University of Bologna
investigator full name: Matteo Ravaioli
investigator title: Principal Investigator
mesh term: Liver Diseases
mesh term: Kidney Diseases
sharing ipd: Yes
ipd description: Individual participant data will be performed by application of a single code.