Kidney ReplacementPOWERNCT06374121
Kidney Perfusion With or Without Absorption
A study testing PerSorb cartridge (CytoSorbents Europe GmbH, Germany) and PerLife PerKidney in people with Kidney Replacement, run by Mario Negri Institute for Pharmacological Research at 1 site in Italy.
Trial summary
In this single-center, pilot, prospective, randomized study, the investigators will compare the biochemical profiles of the perfusate and the functional parameters of five kidneys perfused with Integrated PerLife® system and "PerSorb ECOS-300CY ™" sorbent (adsorption groups) with the profiles of the perfusate and… Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Kidney Replacement
- What is being tested?
- PerSorb cartridge (CytoSorbents Europe GmbH, Germany) and PerLife PerKidney
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteItaly
- Study dates
- 22 Oct 2024to May 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females older than 50 years eligible for single or dual kidney transplant from marginal donors identified according to the NITp criteria (>70-year-old or 60 to 70 years with hypertension and/or diabetes and/or clinical proteinuria)
- Pre-transplant histological evaluation
- Histological score ≤ 7
- Written informed consent.
Who cannot join
- Any factor that represents a contraindication to receive a deceased donor kidney transplant according to the NITp criteria,
- Need for specific desensitization protocols because of a high immunological risk according to the NITp criteria,
- Active enrollment in concomitant intervention studies,
- Macroscopic vascular abnormalities that preclude the possibility of machine perfusion.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Piero L Ruggenenti, MD contact
Italy1 site, 1 recruiting
- Recruiting
ASST - Papa Giovanni XXIII - U.O. Nefrologia e Dialisi/ Mario Negri Institute for Pharmacological Research - Clinical Research Center for Rare Diseases Aldo e Cele Daccò
Bergamo, BG, 24027
Piero Ruggenenti, MD, 0039 035 45351, piero.ruggenenti@marionegri.it
About this study
Official title: A Single-center, Pilot, Prospective, Randomized Clinical Study of Hypothermic Oxygenated Perfusion With or Without Adsorption in Histologically Evaluated Kidneys Retrieved From Marginal Donors
In this single-center, pilot, prospective, randomized study, the investigators will compare the biochemical profiles of the perfusate and the functional parameters of five kidneys perfused with Integrated PerLife® system and "PerSorb ECOS-300CY ™" sorbent (adsorption groups) with the profiles of the perfusate and functional parameters of five matched kidneys perfused with Integrated PerLife® system only (non-adsorption group). Kidneys from marginal donors with a clinical indication to pre-transplant histological evaluation (donor >70-years-old or aged 60 to 69 years but with hypertension, diabetes and/or clinical proteinuria) will be allocated to perfusion with or without adsorption using a 1:1 randomization ratio. When both donor kidneys will have a score from 0 to 4, the two kidneys will be used for two single transplants. When one kidney will have a score from 0 to 4 and the other kidney will have a score of 5 or more, and when both kidneys will have a score from 5 to 7, the two kidneys will be transplanted together into the same recipient. If one kidney will have a score from 5 to 7 and the other kidney will have a score of 8 or greater, the two kidneys will be discarded. With the use of the minimization method, the randomization will be planned in order to have the same number of single or dual transplants in the perfusion kidney groups with or without adsorption. Donor selection, kidney evaluation and allocation and recipient management will be based on per center practice.
Read the detailed description
In recent years, growing interest has been addressed to the use of dynamic preservation of the kidneys as a tool to improve graft function and survival. Retrospective analyses and a randomized controlled trial showed that pre-transplant machine perfusion (MP) is associated with a lower incidence of delayed graft function (DGF) and improved one-year graft survival as compared with static cold storage. However, the overall beneficial effect of MP on transplant outcomes is largely driven by treatment effect in recipients of grafts from marginal donors.
Hypothermic oxygenated perfusion has been found to reduce early allograft injury and to improve post-transplant outcomes in a randomized controlled trial of liver transplantation from older donors. In vitro studies show that perfusion reduces endothelial damage to the sinusoidal capillaries and increases adenosine triphosphate production. As far as kidney transplantation is concerned, little data is available on the outcomes of grafts treated with perfusion. In rat models of allogeneic kidney transplant, perfusion-treated grafts displayed better short-term function, less tubular injury, fewer interstitial infiltrates of immune cells and milder endothelial activation than the untreated counterparts.
MP is not only beneficial per se. It can also be exploited as a means to deliver additional treatment to the graft. For instance, there is in vivo evidence that hemoadsorption improves renal blood flow during perfusion and reduces the release of cytokines and prostaglandins at reperfusion in a porcine model of kidney transplantation. Beneficial effects of hemoadsorption have been documented in the setting of continuous renal replacement treatment for septic shock. In the setting of pre-transplant organ conditioning, cytokine adsorption paired to normothermic perfusion has been found to reduce inflammatory gene expression and increase oxidative phosphorylation pathway gene expression in human kidneys. Whether adsorption paired to perfusion reduces the inflammatory response and whether this is of clinical relevance in transplantation of histologically evaluated kidneys from marginal donors, is worth investigating.
- Conditions
- Kidney Replacement
- Being tested
- PerSorb cartridge (CytoSorbents Europe GmbH, Germany), PerLife PerKidney
- Keywords
- Kidney perfusion, Absorption, Marginal donors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PerSorb cartridge (CytoSorbents Europe GmbH, Germany)Device
This is a highly bio-/hemo-compatible, low-flow resistance polymer cartridge able to remove cytokines and other inflammatory mediators via adsorption.
PerLife PerKidneyDevice
The system for ex vivo kidney reconditioning (Aferetica, Italy), which allows hypothermic oxygenated pulsatile perfusion of the organ.
| Study group | Role | What they receive |
|---|---|---|
| Perfusion and concomitant adsorption | Experimental | Kidneys eligible for perfusion will be treated with the PerLife PerKidney system. Kidneys allocated to the adsorption subgroup will receive concomitant treatment with PerSorb cartridge. Receives: Device: PerSorb cartridge (CytoSorbents Europe GmbH, Germany); Device: PerLife PerKidney |
| Perfusion alone | Active comparator | Kidneys eligible here will only be treated with the PerLife PerKidney system. Receives: Device: PerLife PerKidney |
What is being measured
The primary outcome is the main question the study is designed to answer.
Oxidative stress markers
Glutathione S-transferase (GST), lactate dehydrogenase (LDH) and free lactate
Measured: Every 30 minutes during clinical perfusion
Acute kidney injury markers
Neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and endothelin
Measured: Every 30 minutes during clinical perfusion
Inflammatory cytokine markers
Interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor alpha (TNF-⍺)
Measured: Every 30 minutes during clinical perfusion
Complement activation markers
Complement factor 3a (C3a), complement factor 5a (C5a) and soluble membrane attack complex (sC5bC9)
Measured: Every 30 minutes during clinical perfusion
Vascular resistances
Renal vascular resistances will be automatically collected through clinical perfuzione
Measured: Every 30 minutes during clinical perfusion
Perfusate sample collection
Pseudo-urine ureteral output will be separately assessed at sequential times during clinical perfusion
Measured: At clinical perfusion start, after 1 hour, then after 4 hours from start and every 2 hours thereafter, up to perfusion end
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2024
- Study start22 Oct 2024
- Primary completionMay 2026 (estimated)
- Study completionMay 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Kidney ReplacementStudies 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- To compare the biochemical profiles of the perfusate obtained from 5 kidneys treated with perfusion and concomitant adsorption, with that of the perfusate obtained from 5 kidneys treated with perfusion without adsorption.
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mario Negri Institute for Pharmacological Research
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Giuseppe Remuzzi, MD, Study chair, Istituto Di Ricerche Farmacologiche Mario Negri
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06374121
- Sponsor's protocol ID
- POWER
- Acronym
- POWER
- Status last verified
- Nov 2024
- First submitted
- 10 Apr 2024
- Last updated
- 22 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Remuzzi G, Grinyo J, Ruggenenti P, Beatini M, Cole EH, Milford EL, Brenner BM. Early experience with dual kidney transplantation in adults using expanded donor criteria. Double Kidney Transplant Group (DKG). J Am Soc Nephrol. 1999 Dec;10(12):2591-8. doi: 10.1681/ASN.V10122591.
PubMed 10589699Hosgood SA, Moore T, Kleverlaan T, Adams T, Nicholson ML. Haemoadsorption reduces the inflammatory response and improves blood flow during ex vivo renal perfusion in an experimental model. J Transl Med. 2017 Oct 25;15(1):216. doi: 10.1186/s12967-017-1314-5.
PubMed 29070045Brouwer WP, Duran S, Kuijper M, Ince C. Hemoadsorption with CytoSorb shows a decreased observed versus expected 28-day all-cause mortality in ICU patients with septic shock: a propensity-score-weighted retrospective study. Crit Care. 2019 Sep 18;23(1):317. doi: 10.1186/s13054-019-2588-1.
PubMed 31533846Hosgood SA, Hoff M, Nicholson ML. Treatment of transplant kidneys during machine perfusion. Transpl Int. 2021 Feb;34(2):224-232. doi: 10.1111/tri.13751. Epub 2020 Oct 19.
PubMed 32970886Ferdinand JR, Hosgood SA, Moore T, Ferro A, Ward CJ, Castro-Dopico T, Nicholson ML, Clatworthy MR. Cytokine absorption during human kidney perfusion reduces delayed graft function-associated inflammatory gene signature. Am J Transplant. 2021 Jun;21(6):2188-2199. doi: 10.1111/ajt.16371. Epub 2020 Nov 22.
PubMed 33098231
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-center, Pilot, Prospective, Randomized Clinical Study of Hypothermic Oxygenated Perfusion With or Without Adsorption in Histologically Evaluated Kidneys Retrieved From Marginal Donors
- ClinicalTrials.gov ID
- NCT06374121
- Acronym / sponsor ID
- POWER / POWER
- Conditions
- Kidney Replacement
- Keywords
- Kidney perfusion, Absorption, Marginal donors
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Mario Negri Institute for Pharmacological ResearchUniversity, hospital or other
- Study start
- 22 Oct 2024 (actual)
- Primary completion
- May 2026 (estimated)
- Study completion
- May 2026 (estimated)
- First posted
- 18 Apr 2024 (actual)
- 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.
In this single-center, pilot, prospective, randomized study, the investigators will compare the biochemical profiles of the perfusate and the functional parameters of five kidneys perfused with Integrated PerLife® system and "PerSorb ECOS-300CY ™" sorbent (adsorption groups) with the profiles of the perfusate and functional parameters of five matched kidneys perfused with Integrated PerLife® system only (non-adsorption group). Kidneys from marginal donors with a clinical indication to pre-transplant histological evaluation (donor >70-years-old or aged 60 to 69 years but with hypertension, diabetes and/or clinical proteinuria) will be allocated to perfusion with or without adsorption using a 1:1 randomization ratio. When both donor kidneys will have a score from 0 to 4, the two kidneys will be used for two single transplants. When one kidney will have a score from 0 to 4 and the other kidney will have a score of 5 or more, and when both kidneys will have a score from 5 to 7, the two kidneys will be transplanted together into the same recipient. If one kidney will have a score from 5 to 7 and the other kidney will have a score of 8 or greater, the two kidneys will be discarded. With the use of the minimization method, the randomization will be planned in order to have the same number of single or dual transplants in the perfusion kidney groups with or without adsorption. Donor selection, kidney evaluation and allocation and recipient management will be based on per center practice.
Detailed description
In recent years, growing interest has been addressed to the use of dynamic preservation of the kidneys as a tool to improve graft function and survival. Retrospective analyses and a randomized controlled trial showed that pre-transplant machine perfusion (MP) is associated with a lower incidence of delayed graft function (DGF) and improved one-year graft survival as compared with static cold storage. However, the overall beneficial effect of MP on transplant outcomes is largely driven by treatment effect in recipients of grafts from marginal donors.
Hypothermic oxygenated perfusion has been found to reduce early allograft injury and to improve post-transplant outcomes in a randomized controlled trial of liver transplantation from older donors. In vitro studies show that perfusion reduces endothelial damage to the sinusoidal capillaries and increases adenosine triphosphate production. As far as kidney transplantation is concerned, little data is available on the outcomes of grafts treated with perfusion. In rat models of allogeneic kidney transplant, perfusion-treated grafts displayed better short-term function, less tubular injury, fewer interstitial infiltrates of immune cells and milder endothelial activation than the untreated counterparts.
MP is not only beneficial per se. It can also be exploited as a means to deliver additional treatment to the graft. For instance, there is in vivo evidence that hemoadsorption improves renal blood flow during perfusion and reduces the release of cytokines and prostaglandins at reperfusion in a porcine model of kidney transplantation. Beneficial effects of hemoadsorption have been documented in the setting of continuous renal replacement treatment for septic shock. In the setting of pre-transplant organ conditioning, cytokine adsorption paired to normothermic perfusion has been found to reduce inflammatory gene expression and increase oxidative phosphorylation pathway gene expression in human kidneys. Whether adsorption paired to perfusion reduces the inflammatory response and whether this is of clinical relevance in transplantation of histologically evaluated kidneys from marginal donors, is worth investigating.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- To compare the biochemical profiles of the perfusate obtained from 5 kidneys treated with perfusion and concomitant adsorption, with that of the perfusate obtained from 5 kidneys treated with perfusion without adsorption.
| Arm | Type | Receives |
|---|---|---|
| Perfusion and concomitant adsorption | Experimental | Device: PerSorb cartridge (CytoSorbents Europe GmbH, Germany), Device: PerLife PerKidneyKidneys eligible for perfusion will be treated with the PerLife PerKidney system. Kidneys allocated to the adsorption subgroup will receive concomitant treatment with PerSorb cartridge. |
| Perfusion alone | Active comparator | Device: PerLife PerKidneyKidneys eligible here will only be treated with the PerLife PerKidney system. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Males and females older than 50 years eligible for single or dual kidney transplant from marginal donors identified according to the NITp criteria (>70-year-old or 60 to 70 years with hypertension and/or diabetes and/or clinical proteinuria)
- Pre-transplant histological evaluation
- Histological score ≤ 7
- Written informed consent.
Key exclusion criteria (4 listed)
- Any factor that represents a contraindication to receive a deceased donor kidney transplant according to the NITp criteria,
- Need for specific desensitization protocols because of a high immunological risk according to the NITp criteria,
- Active enrollment in concomitant intervention studies,
- Macroscopic vascular abnormalities that preclude the possibility of machine perfusion.
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 |
|---|---|---|
| PerSorb cartridge (CytoSorbents Europe GmbH, Germany)This is a highly bio-/hemo-compatible, low-flow resistance polymer cartridge able to remove cytokines and other inflammatory mediators via adsorption. | Device | Perfusion and concomitant adsorption |
| PerLife PerKidneyThe system for ex vivo kidney reconditioning (Aferetica, Italy), which allows hypothermic oxygenated pulsatile perfusion of the organ. | Device | Perfusion alone, Perfusion and concomitant adsorption |
Primary outcome
Oxidative stress markers
Time frame: Every 30 minutes during clinical perfusion
Glutathione S-transferase (GST), lactate dehydrogenase (LDH) and free lactate
Acute kidney injury markers
Time frame: Every 30 minutes during clinical perfusion
Neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and endothelin
Inflammatory cytokine markers
Time frame: Every 30 minutes during clinical perfusion
Interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor alpha (TNF-⍺)
Complement activation markers
Time frame: Every 30 minutes during clinical perfusion
Complement factor 3a (C3a), complement factor 5a (C5a) and soluble membrane attack complex (sC5bC9)
Vascular resistances
Time frame: Every 30 minutes during clinical perfusion
Renal vascular resistances will be automatically collected through clinical perfuzione
Perfusate sample collection
Time frame: At clinical perfusion start, after 1 hour, then after 4 hours from start and every 2 hours thereafter, up to perfusion end
Pseudo-urine ureteral output will be separately assessed at sequential times during clinical perfusion
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2024.
- Background: PubMed 10589699Remuzzi G, Grinyo J, Ruggenenti P, Beatini M, Cole EH, Milford EL, Brenner BM. Early experience with dual kidney transplantation in adults using expanded donor criteria. Double Kidney Transplant Group (DKG). J Am Soc Nephrol. 1999 Dec;10(12):2591-8. doi: 10.1681/ASN.V10122591.
- Background: PubMed 29070045Hosgood SA, Moore T, Kleverlaan T, Adams T, Nicholson ML. Haemoadsorption reduces the inflammatory response and improves blood flow during ex vivo renal perfusion in an experimental model. J Transl Med. 2017 Oct 25;15(1):216. doi: 10.1186/s12967-017-1314-5.
- Background: PubMed 31533846Brouwer WP, Duran S, Kuijper M, Ince C. Hemoadsorption with CytoSorb shows a decreased observed versus expected 28-day all-cause mortality in ICU patients with septic shock: a propensity-score-weighted retrospective study. Crit Care. 2019 Sep 18;23(1):317. doi: 10.1186/s13054-019-2588-1.
- Background: PubMed 32970886Hosgood SA, Hoff M, Nicholson ML. Treatment of transplant kidneys during machine perfusion. Transpl Int. 2021 Feb;34(2):224-232. doi: 10.1111/tri.13751. Epub 2020 Oct 19.
- Background: PubMed 33098231Ferdinand JR, Hosgood SA, Moore T, Ferro A, Ward CJ, Castro-Dopico T, Nicholson ML, Clatworthy MR. Cytokine absorption during human kidney perfusion reduces delayed graft function-associated inflammatory gene signature. Am J Transplant. 2021 Jun;21(6):2188-2199. doi: 10.1111/ajt.16371. Epub 2020 Nov 22.
- Individual participant dataSharing planned: No
Related trials for Kidney Replacement
Recruiting
Neutrophil and Monocyte Deactivation Via the SeLective CytopheretIc Device - A Randomized Clinical Trial in Acute Kidney Injury
Acute Kidney Injury
Recruiting
Effect of High Versus Standard Protein Intake in Critically Ill Patients With Acute Kidney Injury Requiring Continuous Renal Replacement Therapy
Acute Kidney Failure Stage 3, Continuous Renal Replacement Therapy (CRRT)
RecruitingPhase 3
Safety Evaluation of Prismocitrate 18 in Patients Receiving CRRT
Regional Citrate Anticoagulation (RCA), Continuous Renal Replacement Therapy (CRRT)
Recruiting
Fluid Balance Guided by Modified Venous Excess Ultrasonography Versus Standard Care in Patients With Acute Kidney Injury Receiving Continuous Renal Replacement Therapy
AKI - Acute Kidney Injury, Fluid Balance
Recruiting
WIN Ratio Analysis to Determine a Strategy of Non- Invasive SUpport for Respiratory Failure in the EmeRgency Department
Acute Hypoxic Respiratory Failure, Acute Respiratory Distress Syndrome (ARDS)
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.
Piero L Ruggenenti, MD contact
Giuseppe Remuzzi, MD study chair
Istituto Di Ricerche Farmacologiche Mario Negri
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PerSorb cartridge (CytoSorbents Europe GmbH, Germany) and PerLife PerKidney in people with Kidney Replacement, run by Mario Negri Institute for Pharmacological Research 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: looking for participants now, as of the sponsor's last update on 22 Nov 2024. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Camillo Carrara, MD (+3903545351, pruggenenti@asst-pg23.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Oxidative stress markers (time frame: Every 30 minutes during clinical perfusion). The study lists 6 primary outcomes in all. 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 NCT06374121, which also lists 5 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 22 Nov 2024.