Inflammatory ResponseIMHeSNCT04157647
Hemadsorption During and After Cardiopulmonary Bypass to Modulate the Inflammatory Response
A study testing CytoSorb in people with Inflammatory Response and Chronic Renal Disease, run by University Magna Graecia at 1 site in Italy.
Trial summary
Chronic kidney disease (CKD) is a risk factor for the development of cardiovascular disease, which increases the risk of death after cardiac surgery. High interleukin 6 (IL-6) blood levels is commonly observed in patients with CKD, and this is particularly high after cardiac surgery. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Inflammatory Response, Chronic Renal Disease, Cardiac Surgery
- What is being tested?
- CytoSorb
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteItaly
- Study dates
- 15 Nov 2020to 15 Nov 2021
- 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 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- All consecutive adult patients (age >65 years) undergoing cardiac surgery with an anticipated CPB time duration longer than 60 minutes.
- Presence of CKD defined by a Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73 m2.
- Consent to participate to the study
Who cannot join
- emergency surgery
- acute infective endocarditis
- systemic infectious diseases
- previous kidney transplant
- need for contrast enhancement during surgery
- immunosuppressive or long-term corticosteroid therapies
- participation to other investigations.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Monocentric Prospective Randomized Pilot Study in Patients With Kidney Failure to Evaluate the Relationship Between the Hemadsorption During and After Cardiopulmonary Bypass and the Modulation of Post-surgical Inflammatory Response
Chronic kidney disease (CKD) is a risk factor for the development of cardiovascular disease, which increases the risk of death after cardiac surgery. High interleukin 6 (IL-6) blood levels is commonly observed in patients with CKD, and this is particularly high after cardiac surgery. High IL-6 levels are also associated with increased long-term mortality rate after cardiac surgery. To date, the use of ultrafiltration or endotoxin adsorption systems were not found to improve the clinical outcome, although able to reduce the inflammatory mediators concentrations. In the last years, a new extracorporeal hemadsorption filter (CytoSorb) has been developed for removal of inflammatory cytokines and it has been approved by the European Union. However, data lack about the impact on clinical outcome of the use of CytoSorb in patients with CKD undergoing cardiac surgery with cardio-pulmonary bypass (CPB). The investigators have therefore designed this pilot prospective randomized trial to evaluate the efficacy the intraoperative use of CytoSorb for cytokines removal to prevent the inflammatory response associated with the cardiac surgery and complications in patients with CKD.
- Being tested
- CytoSorb, Control
- Keywords
- hemadsorption
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CytoSorbDevice
The hemadsorption filter will be included in the CPB circuit between the oxygenator and the venous reservoir. After cardiac surgery, the use of the filter will be continued till 24 hours after the end of surgery.
ControlDevice
No hemadsorption filter or other treatment will be included in the CPB circuit
| Study group | Role | What they receive |
|---|---|---|
| CytoSorb | Active comparator | Patients assigned to this arm group will receive hemadsorption witbhCytoSorb during the surgery and in the next 24 hours after surgery. Receives: Device: CytoSorb |
| Control | Sham comparator | Patients assigned to this arm group will undergo to a normal CPB without the use of any hemoadsorption system. Receives: Device: Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
IL-6 concentration at ICU admission
Investigators will assess the blood IL-6 concentrations between the two arms
Measured: At day 0 after surgery
Secondary outcomes (10)
IL-6 concentration before cardiac surgery
Investigators will assess the blood IL-6 concentrations between the two arms
Measured: At day 0 before the cardiac surgery
IL-6 concentration at the end of CardioPulmonary Bypass
Investigators will assess the blood IL-6 concentrations between the two arms
Measured: At day 0 at the end of the CardioPulmonary Bypass
IL-6 concentration 2 hours after the end of CardioPulmonary Bypass
Investigators will assess the blood IL-6 concentrations between the two arms
Measured: 2 hours after the end of CardioPulmonary Bypass
IL-6 concentration 48 hours after the end of CardioPulmonary Bypass
Investigators will assess the blood IL-6 concentrations between the two arms
Measured: 48 hours after the end of CardioPulmonary Bypass
Renal function
Investigators will assess the blood creatinine concentrations in the two arms
Measured: daily up to day 15
Myoglobin concentration
Investigators will assess the blood myoglobin concentrations in the two arms
Measured: daily up to day 15
Haptoglobin concentration
Investigators will assess the blood haptoglobin concentrations in the two arms
Measured: daily up to day 15
Liver transaminases concentration
Investigators will measure the liver transaminases concentrations in the two arms to assess any liver injury
Measured: daily up to day 15
Osteopontin concentration
Investigators will measure the osteopontin concentrations in the two arms to assess the inflammatory status
Measured: daily up to day 15
Free hemoglobin concentration
Investigators will assess the free hemoglobin concentrations in the two arms
Measured: daily up to day 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2019
- Study start15 Nov 2020 (estimated)
- Primary completion1 Nov 2021 (estimated)
- Study completion15 Nov 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Inflammatory ResponseStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Magna Graecia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, GIUSEPPE FILIBERTO SERRAINO, University Magna Graecia
- Investigators
- Giuseppe Serraino, MD, Principal investigator, Magna Graecia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04157647
- Sponsor's protocol ID
- IMHeS
- Acronym
- IMHeS
- Status last verified
- Nov 2020
- First submitted
- 13 Oct 2019
- Last updated
- 12 Nov 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The full protocol, datasets used and analysed during the current study will be available on reasonable request after study publication
Publications
Tonelli M, Wiebe N, Culleton B, House A, Rabbat C, Fok M, McAlister F, Garg AX. Chronic kidney disease and mortality risk: a systematic review. J Am Soc Nephrol. 2006 Jul;17(7):2034-47. doi: 10.1681/ASN.2005101085. Epub 2006 May 31.
PubMed 16738019Penta de Peppo A, Nardi P, De Paulis R, Pellegrino A, Forlani S, Scafuri A, Chiariello L. Cardiac surgery in moderate to end-stage renal failure: analysis of risk factors. Ann Thorac Surg. 2002 Aug;74(2):378-83. doi: 10.1016/s0003-4975(02)03711-6.
PubMed 12173816Durmaz I, Buket S, Atay Y, Yagdi T, Ozbaran M, Boga M, Alat I, Guzelant A, Basarir S. Cardiac surgery with cardiopulmonary bypass in patients with chronic renal failure. J Thorac Cardiovasc Surg. 1999 Aug;118(2):306-15. doi: 10.1016/S0022-5223(99)70221-7.
PubMed 10425004Pecoits-Filho R, Heimburger O, Barany P, Suliman M, Fehrman-Ekholm I, Lindholm B, Stenvinkel P. Associations between circulating inflammatory markers and residual renal function in CRF patients. Am J Kidney Dis. 2003 Jun;41(6):1212-8. doi: 10.1016/s0272-6386(03)00353-6.
PubMed 12776273Takahashi T, Kubota M, Nakamura T, Ebihara I, Koide H. Interleukin-6 gene expression in peripheral blood mononuclear cells from patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis. Ren Fail. 2000 May;22(3):345-54. doi: 10.1081/jdi-100100878.
PubMed 10843245Caglar K, Peng Y, Pupim LB, Flakoll PJ, Levenhagen D, Hakim RM, Ikizler TA. Inflammatory signals associated with hemodialysis. Kidney Int. 2002 Oct;62(4):1408-16. doi: 10.1111/j.1523-1755.2002.kid556.x.
PubMed 12234313Corral-Velez V, Lopez-Delgado JC, Betancur-Zambrano NL, Lopez-Sune N, Rojas-Lora M, Torrado H, Ballus J. The inflammatory response in cardiac surgery: an overview of the pathophysiology and clinical implications. Inflamm Allergy Drug Targets. 2015;13(6):367-70. doi: 10.2174/1871528114666150529120801.
PubMed 26021321de Amorim CG, Malbouisson LM, da Silva FC Jr, Fiorelli AI, Murakami CK, Carmona MJ. Leukocyte depletion during CPB: effects on inflammation and lung function. Inflammation. 2014 Feb;37(1):196-204. doi: 10.1007/s10753-013-9730-z.
PubMed 24092406Ilmakunnas M, Pesonen EJ, Ahonen J, Ramo J, Siitonen S, Repo H. Activation of neutrophils and monocytes by a leukocyte-depleting filter used throughout cardiopulmonary bypass. J Thorac Cardiovasc Surg. 2005 Apr;129(4):851-9. doi: 10.1016/j.jtcvs.2004.07.061.
PubMed 15821654Wiegele M, Krenn CG. Cytosorb in a patient with Legionella pneumonia-associated rhabdomyolysis: a case report. ASAIO J. 2015 May-Jun;61(3):e14-6. doi: 10.1097/MAT.0000000000000197. No abstract available.
PubMed 25635933Basu R, Pathak S, Goyal J, Chaudhry R, Goel RB, Barwal A. Use of a novel hemoadsorption device for cytokine removal as adjuvant therapy in a patient with septic shock with multi-organ dysfunction: A case study. Indian J Crit Care Med. 2014 Dec;18(12):822-4. doi: 10.4103/0972-5229.146321.
PubMed 25538418Hetz H, Berger R, Recknagel P, Steltzer H. Septic shock secondary to beta-hemolytic streptococcus-induced necrotizing fasciitis treated with a novel cytokine adsorption therapy. Int J Artif Organs. 2014 May;37(5):422-6. doi: 10.5301/ijao.5000315. Epub 2014 Apr 17.
PubMed 24811308Vercaemst L. Hemolysis in cardiac surgery patients undergoing cardiopulmonary bypass: a review in search of a treatment algorithm. J Extra Corpor Technol. 2008 Dec;40(4):257-67.
PubMed 19192755Kahles F, Findeisen HM, Bruemmer D. Osteopontin: A novel regulator at the cross roads of inflammation, obesity and diabetes. Mol Metab. 2014 Mar 22;3(4):384-93. doi: 10.1016/j.molmet.2014.03.004. eCollection 2014 Jul.
PubMed 24944898Baumann A, Buchwald D, Annecke T, Hellmich M, Zahn PK, Hohn A. RECCAS - REmoval of Cytokines during CArdiac Surgery: study protocol for a randomised controlled trial. Trials. 2016 Mar 12;17(1):137. doi: 10.1186/s13063-016-1265-9.
PubMed 26971164
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Monocentric Prospective Randomized Pilot Study in Patients With Kidney Failure to Evaluate the Relationship Between the Hemadsorption During and After Cardiopulmonary Bypass and the Modulation of Post-surgical Inflammatory Response
- ClinicalTrials.gov ID
- NCT04157647
- Acronym / sponsor ID
- IMHeS / IMHeS
- Keywords
- hemadsorption
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University Magna GraeciaUniversity, hospital or other
- Study start
- 15 Nov 2020 (estimated)
- Primary completion
- 1 Nov 2021 (estimated)
- Study completion
- 15 Nov 2021 (estimated)
- First posted
- 8 Nov 2019 (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.
Chronic kidney disease (CKD) is a risk factor for the development of cardiovascular disease, which increases the risk of death after cardiac surgery. High interleukin 6 (IL-6) blood levels is commonly observed in patients with CKD, and this is particularly high after cardiac surgery. High IL-6 levels are also associated with increased long-term mortality rate after cardiac surgery. To date, the use of ultrafiltration or endotoxin adsorption systems were not found to improve the clinical outcome, although able to reduce the inflammatory mediators concentrations. In the last years, a new extracorporeal hemadsorption filter (CytoSorb) has been developed for removal of inflammatory cytokines and it has been approved by the European Union. However, data lack about the impact on clinical outcome of the use of CytoSorb in patients with CKD undergoing cardiac surgery with cardio-pulmonary bypass (CPB). The investigators have therefore designed this pilot prospective randomized trial to evaluate the efficacy the intraoperative use of CytoSorb for cytokines removal to prevent the inflammatory response associated with the cardiac surgery and complications in patients with CKD.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CytoSorb | Active comparator | Device: CytoSorbPatients assigned to this arm group will receive hemadsorption witbhCytoSorb during the surgery and in the next 24 hours after surgery. |
| Control | Sham comparator | Device: ControlPatients assigned to this arm group will undergo to a normal CPB without the use of any hemoadsorption system. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (3 listed)
- All consecutive adult patients (age >65 years) undergoing cardiac surgery with an anticipated CPB time duration longer than 60 minutes.
- Presence of CKD defined by a Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73 m2.
- Consent to participate to the study
Key exclusion criteria (7 listed)
- emergency surgery
- acute infective endocarditis
- systemic infectious diseases
- previous kidney transplant
- need for contrast enhancement during surgery
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 |
|---|---|---|
| CytoSorbThe hemadsorption filter will be included in the CPB circuit between the oxygenator and the venous reservoir. After cardiac surgery, the use of the filter will be continued till 24 hours after the end of surgery. | Device | CytoSorb |
| ControlNo hemadsorption filter or other treatment will be included in the CPB circuit | Device | Control |
Primary outcome
IL-6 concentration at ICU admission
Time frame: At day 0 after surgery
Investigators will assess the blood IL-6 concentrations between the two arms
10 secondary outcomes
IL-6 concentration before cardiac surgery
Time frame: At day 0 before the cardiac surgery
IL-6 concentration at the end of CardioPulmonary Bypass
Time frame: At day 0 at the end of the CardioPulmonary Bypass
IL-6 concentration 2 hours after the end of CardioPulmonary Bypass
Time frame: 2 hours after the end of CardioPulmonary Bypass
IL-6 concentration 48 hours after the end of CardioPulmonary Bypass
Time frame: 48 hours after the end of CardioPulmonary Bypass
Renal function
Time frame: daily up to day 15
Myoglobin concentration
Time frame: daily up to day 15
Haptoglobin concentration
Time frame: daily up to day 15
Liver transaminases concentration
Time frame: daily up to day 15
Osteopontin concentration
Time frame: daily up to day 15
Free hemoglobin concentration
Time frame: daily up to day 15
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2020.
- Background: PubMed 16738019Tonelli M, Wiebe N, Culleton B, House A, Rabbat C, Fok M, McAlister F, Garg AX. Chronic kidney disease and mortality risk: a systematic review. J Am Soc Nephrol. 2006 Jul;17(7):2034-47. doi: 10.1681/ASN.2005101085. Epub 2006 May 31.
- Background: PubMed 12173816Penta de Peppo A, Nardi P, De Paulis R, Pellegrino A, Forlani S, Scafuri A, Chiariello L. Cardiac surgery in moderate to end-stage renal failure: analysis of risk factors. Ann Thorac Surg. 2002 Aug;74(2):378-83. doi: 10.1016/s0003-4975(02)03711-6.
- Background: PubMed 10425004Durmaz I, Buket S, Atay Y, Yagdi T, Ozbaran M, Boga M, Alat I, Guzelant A, Basarir S. Cardiac surgery with cardiopulmonary bypass in patients with chronic renal failure. J Thorac Cardiovasc Surg. 1999 Aug;118(2):306-15. doi: 10.1016/S0022-5223(99)70221-7.
- Background: PubMed 12776273Pecoits-Filho R, Heimburger O, Barany P, Suliman M, Fehrman-Ekholm I, Lindholm B, Stenvinkel P. Associations between circulating inflammatory markers and residual renal function in CRF patients. Am J Kidney Dis. 2003 Jun;41(6):1212-8. doi: 10.1016/s0272-6386(03)00353-6.
- Background: PubMed 10843245Takahashi T, Kubota M, Nakamura T, Ebihara I, Koide H. Interleukin-6 gene expression in peripheral blood mononuclear cells from patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis. Ren Fail. 2000 May;22(3):345-54. doi: 10.1081/jdi-100100878.
- Background: PubMed 12234313Caglar K, Peng Y, Pupim LB, Flakoll PJ, Levenhagen D, Hakim RM, Ikizler TA. Inflammatory signals associated with hemodialysis. Kidney Int. 2002 Oct;62(4):1408-16. doi: 10.1111/j.1523-1755.2002.kid556.x.
- Background: PubMed 26021321Corral-Velez V, Lopez-Delgado JC, Betancur-Zambrano NL, Lopez-Sune N, Rojas-Lora M, Torrado H, Ballus J. The inflammatory response in cardiac surgery: an overview of the pathophysiology and clinical implications. Inflamm Allergy Drug Targets. 2015;13(6):367-70. doi: 10.2174/1871528114666150529120801.
- Background: PubMed 24092406de Amorim CG, Malbouisson LM, da Silva FC Jr, Fiorelli AI, Murakami CK, Carmona MJ. Leukocyte depletion during CPB: effects on inflammation and lung function. Inflammation. 2014 Feb;37(1):196-204. doi: 10.1007/s10753-013-9730-z.
- Background: PubMed 15821654Ilmakunnas M, Pesonen EJ, Ahonen J, Ramo J, Siitonen S, Repo H. Activation of neutrophils and monocytes by a leukocyte-depleting filter used throughout cardiopulmonary bypass. J Thorac Cardiovasc Surg. 2005 Apr;129(4):851-9. doi: 10.1016/j.jtcvs.2004.07.061.
- Background: PubMed 25635933Wiegele M, Krenn CG. Cytosorb in a patient with Legionella pneumonia-associated rhabdomyolysis: a case report. ASAIO J. 2015 May-Jun;61(3):e14-6. doi: 10.1097/MAT.0000000000000197. No abstract available.
- Background: PubMed 25538418Basu R, Pathak S, Goyal J, Chaudhry R, Goel RB, Barwal A. Use of a novel hemoadsorption device for cytokine removal as adjuvant therapy in a patient with septic shock with multi-organ dysfunction: A case study. Indian J Crit Care Med. 2014 Dec;18(12):822-4. doi: 10.4103/0972-5229.146321.
- Background: PubMed 24811308Hetz H, Berger R, Recknagel P, Steltzer H. Septic shock secondary to beta-hemolytic streptococcus-induced necrotizing fasciitis treated with a novel cytokine adsorption therapy. Int J Artif Organs. 2014 May;37(5):422-6. doi: 10.5301/ijao.5000315. Epub 2014 Apr 17.
- Individual participant dataSharing planned: Yes. The full protocol, datasets used and analysed during the current study will be available on reasonable request after study publication
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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.
Giuseppe Serraino, MD principal investigator
Magna Graecia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CytoSorb in people with Inflammatory Response and Chronic Renal Disease, run by University Magna Graecia 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 3 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 12 Nov 2020. 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. Some participants in this study may receive a placebo. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Giuseppe F Serraino, MD (0039 0961 3647033, filiberto@live.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
IL-6 concentration at ICU admission (time frame: At day 0 after surgery). 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 NCT04157647, which also lists 15 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 12 Nov 2020.