Liver DiseasesPIONCT03031067
Hypothermic Oxygenated Perfusion Versus Static Cold Storage for Marginal Graft
A study testing Machine perfusion in people with Liver Diseases and Kidney Diseases, run by Matteo Ravaioli at 1 site in Italy.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Liver Diseases, Kidney Diseases
- What is being tested?
- Machine perfusion
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- Oct 2016to Feb 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Kidney donor: ECD.
- Kidney recipient: single or dual kidney transplant recipients at our center, provided consent.
- Liver donor: ECD
- Liver recipient: liver transplant recipients at our center, provided consent.
Who cannot join
- Kidney donor: no ECD, donor with vascular anatomical abnormalities and/or urinary tract, donor with a risk infection, to increase cold ischemia time can not be avoided.
- Kidney recipient: patients with severe atherosclerotic vascular disease, pathologies predisposing to the onset of intra-operative surgical complications, such as thrombophilia and hemophilia, antigenic incompatibility with donor determining the acute rejection of the organ; patients waiting for kidney transplant pre-emptive, multi-organ transplant, retransplantation.
- Liver donor: no ECD, donor with vascular anatomical abnormalities, donor with a risk infection, to increase cold ischemia time can not be avoided.
- Liver recipient: patients with acute liver disease and with vascular abnormalities and/or biliary tract requiring non-conventional reconstructive techniques, patients waiting for multi-organ transplant, retransplantation, urgency transplant ( or with MELD>30).
Trial locations and contacts
1 site in 1 country.
Italy1 site
Azienda Ospedaliera di Bologna - Policlinico S. Orsola Malpighi
Bologna, 40138
About this study
Official title: Comparison Between Hypothermic Oxygenated Perfusion and Static Cold Storage of Organ From Extended Criteria Donors
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.
Read the detailed description
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.
- Conditions
- Liver Diseases, Kidney Diseases
- Being tested
- Machine perfusion
- Keywords
- Donors and donation, Extended criteria donor, Organ perfusion and preservation, Liver transplantation, Kidney transplantation, Preservation injury, Ischemia reperfusion injury
- Medical subject headings
- Liver Diseases, Kidney Diseases, Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Machine perfusionDevice
Also called Hypothermic Oxygenated Perfusion
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.
| Study group | Role | What they receive |
|---|---|---|
| Machine perfusion - Kidney | Experimental | The marginal kidney will be perfused with oxygenated solution of preservation at 4°C for two hours with Exiper, Bologna Machine Perfusion. Receives: Device: Machine perfusion |
| Static cold storage - Kidney | No intervention | The marginal kidney that was stored to cold (SCS), previously. |
| Machine perfusion - Liver | Experimental | The marginal liver will be perfused with oxygenated solution of preservation at 4°C for two hours with Exiper, Bologna Machine Perfusion. Receives: Device: Machine perfusion |
| Static cold storage - Liver | No intervention | The marginal liver that was stored to cold (SCS), previously. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Graft function
Physiological values of serum creatinine and diuresis for kidney transplantation and bilirubin, AST, ALT, INR for liver transplantation
Measured: 3 months post-transplantation (+18/-2 months)
Secondary outcomes (4)
Graft survival - Kidney
Time (days) of graft survival
Measured: 3 months post-transplantation (+18/-2 months)
Graft survival - Liver
Time (days) of graft survival
Measured: 3 months post-transplantation (+18/-2 months)
Patient survival (kidney recipient)
Time (days) of patient survival
Measured: 3 months post-transplantation (+18/-2 months)
Patient survival (liver recipient)
Time (days) of patient survival
Measured: 3 months post-transplantation (+18/-2 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2017 (estimated)
- Study startOct 2016
- Primary completionDec 2017
- Study completionFeb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Liver DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Matteo Ravaioli
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Matteo Ravaioli, University of Bologna
- Investigators
- Matteo Ravaioli, PhD, Principal investigator, University of Bologna S. Orsola-Malpighi Hospital, Transplantation and General Surgery UnitAntonio Daniele Pinna, Professor, Study director, University of Bologna S. Orsola-Malpighi Hospital, Transplantation and General Surgery Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03031067
- Sponsor's protocol ID
- PIO-700
- Other IDs
- 159/2015/O/Disp
- Acronym
- PIO
- Status last verified
- Feb 2018
- First submitted
- 19 Jan 2017
- Last updated
- 13 Feb 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Individual participant data will be performed by application of a single code.
Publications
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.
PubMed 23754643Thuillier 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.
PubMed 23731682Hosgood SA, Nicholson HF, Nicholson ML. Oxygenated kidney preservation techniques. Transplantation. 2012 Mar 15;93(5):455-9. doi: 10.1097/TP.0b013e3182412b34.
PubMed 22217529Dutkowski 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.
PubMed 26583664
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison Between Hypothermic Oxygenated Perfusion and Static Cold Storage of Organ From Extended Criteria Donors
- ClinicalTrials.gov ID
- NCT03031067
- Acronym / sponsor ID
- PIO / PIO-700
- Conditions
- Liver Diseases, Kidney Diseases
- Keywords
- Donors and donation, Extended criteria donor, Organ perfusion and preservation, Liver transplantation, Kidney transplantation, Preservation injury, Ischemia reperfusion injury
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Matteo RavaioliUniversity, hospital or other
- Study start
- Oct 2016
- Primary completion
- Dec 2017 (actual)
- Study completion
- Feb 2018 (actual)
- First posted
- 25 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- 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.
| Arm | Type | Receives |
|---|---|---|
| Machine perfusion - Kidney | Experimental | Device: Machine perfusionThe marginal kidney will be perfused with oxygenated solution of preservation at 4°C for two hours with Exiper, Bologna Machine Perfusion. |
| Static cold storage - Kidney | No intervention | –The marginal kidney that was stored to cold (SCS), previously. |
| Machine perfusion - Liver | Experimental | Device: Machine perfusionThe marginal liver will be perfused with oxygenated solution of preservation at 4°C for two hours with Exiper, Bologna Machine Perfusion. |
| Static cold storage - Liver | No intervention | –The marginal liver that was stored to cold (SCS), previously. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Kidney donor: ECD.
- Kidney recipient: single or dual kidney transplant recipients at our center, provided consent.
- Liver donor: ECD
- Liver recipient: liver transplant recipients at our center, provided consent.
Key exclusion criteria (4 listed)
- Kidney donor: no ECD, donor with vascular anatomical abnormalities and/or urinary tract, donor with a risk infection, to increase cold ischemia time can not be avoided.
- Kidney recipient: patients with severe atherosclerotic vascular disease, pathologies predisposing to the onset of intra-operative surgical complications, such as thrombophilia and hemophilia, antigenic incompatibility with donor determining the acute rejection of the organ; patients waiting for kidney transplant pre-emptive, multi-organ transplant, retransplantation.
- Liver donor: no ECD, donor with vascular anatomical abnormalities, donor with a risk infection, to increase cold ischemia time can not be avoided.
- Liver recipient: patients with acute liver disease and with vascular abnormalities and/or biliary tract requiring non-conventional reconstructive techniques, patients waiting for multi-organ transplant, retransplantation, urgency transplant ( or with MELD>30).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Machine perfusionAlso: Hypothermic Oxygenated PerfusionThe 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. | Device | Machine perfusion - Kidney, Machine perfusion - Liver |
Primary outcome
Graft function
Time frame: 3 months post-transplantation (+18/-2 months)
Physiological values of serum creatinine and diuresis for kidney transplantation and bilirubin, AST, ALT, INR for liver transplantation
4 secondary outcomes
Graft survival - Kidney
Time frame: 3 months post-transplantation (+18/-2 months)
Graft survival - Liver
Time frame: 3 months post-transplantation (+18/-2 months)
Patient survival (kidney recipient)
Time frame: 3 months post-transplantation (+18/-2 months)
Patient survival (liver recipient)
Time frame: 3 months post-transplantation (+18/-2 months)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2018.
- Background: PubMed 23754643O'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.
- Background: PubMed 23731682Thuillier 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.
- Background: PubMed 22217529Hosgood SA, Nicholson HF, Nicholson ML. Oxygenated kidney preservation techniques. Transplantation. 2012 Mar 15;93(5):455-9. doi: 10.1097/TP.0b013e3182412b34.
- Background: PubMed 26583664Dutkowski 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.
- Individual participant dataSharing planned: Yes. Individual participant data will be performed by application of a single code.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matteo Ravaioli, PhD principal investigator
University of Bologna S. Orsola-Malpighi Hospital, Transplantation and General Surgery Unit
Antonio Daniele Pinna, Professor study director
University of Bologna S. Orsola-Malpighi Hospital, Transplantation and General Surgery Unit
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Machine perfusion in people with Liver Diseases and Kidney Diseases, run by Matteo Ravaioli at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Graft function (time frame: 3 months post-transplantation (+18/-2 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03031067, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2018.