Hemadsorption During and After Cardiopulmonary Bypass to Modulate the Inflammatory Response

Cardiac Surgery Clinical Trial

— IMHeS  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04157647
• Other study ID #: IMHeS
• Status: Not yet recruiting
• Phase: N/A
• Start date: November 15, 2020
• Est. completion date: November 15, 2021

Study information

• Verified date: November 2020
• Source: University Magna Graecia
• Contact: Giuseppe F Serraino, MD
• Phone: 0039 0961 3647033
• Email: filiberto[@]live.it
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: November 15, 2021
• Est. primary completion date: November 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Cardiac Surgery
• Chronic Renal Disease
• Inflammatory Response
• Kidney Failure, Chronic
• Renal Insufficiency, Chronic

Intervention

Device:
• CytoSorb
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.
• Control
No hemadsorption filter or other treatment will be included in the CPB circuit

Locations

Country	Name	City	State
Italy	AOU Mater Domini	Catanzaro	CZ

Sponsors (1)

Lead Sponsor	Collaborator
University Magna Graecia

Country where clinical trial is conducted

Italy, 

References & Publications (15)

Basu 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. — View Citation

Baumann 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. — View Citation

Caglar 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. — View Citation

Corral-Velez V, Lopez-Delgado JC, Betancur-Zambrano NL, Lopez-Suñe 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. Review. — View Citation

de 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. — View Citation

Durmaz I, Büket S, Atay Y, Yagdi T, Ozbaran M, Boga M, Alat I, Güzelant A, Basarir S. Cardiac surgery with cardiopulmonary bypass in patients with chronic renal failure. J Thorac Cardiovasc Surg. 1999 Aug;118(2):306-15. — View Citation

Hetz H, Berger R, Recknagel P, Steltzer H. Septic shock secondary to ß-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. — View Citation

Ilmakunnas M, Pesonen EJ, Ahonen J, Rämö 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. — View Citation

Kahles 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. Review. — View Citation

Pecoits-Filho R, Heimbürger O, Bárány 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. — View Citation

Penta 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. — View Citation

Takahashi 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. — View Citation

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. Epub 2006 May 31. Review. — View Citation

Vercaemst 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. Review. — View Citation

Wiegele 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. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	IL-6 concentration at ICU admission	Investigators will assess the blood IL-6 concentrations between the two arms	At day 0 after surgery
Secondary	IL-6 concentration before cardiac surgery	Investigators will assess the blood IL-6 concentrations between the two arms	At day 0 before the cardiac surgery
Secondary	IL-6 concentration at the end of CardioPulmonary Bypass	Investigators will assess the blood IL-6 concentrations between the two arms	At day 0 at the end of the CardioPulmonary Bypass
Secondary	IL-6 concentration 2 hours after the end of CardioPulmonary Bypass	Investigators will assess the blood IL-6 concentrations between the two arms	2 hours after the end of CardioPulmonary Bypass
Secondary	IL-6 concentration 48 hours after the end of CardioPulmonary Bypass	Investigators will assess the blood IL-6 concentrations between the two arms	48 hours after the end of CardioPulmonary Bypass
Secondary	Renal function	Investigators will assess the blood creatinine concentrations in the two arms	daily up to day 15
Secondary	Myoglobin concentration	Investigators will assess the blood myoglobin concentrations in the two arms	daily up to day 15
Secondary	Haptoglobin concentration	Investigators will assess the blood haptoglobin concentrations in the two arms	daily up to day 15
Secondary	Liver transaminases concentration	Investigators will measure the liver transaminases concentrations in the two arms to assess any liver injury	daily up to day 15
Secondary	Osteopontin concentration	Investigators will measure the osteopontin concentrations in the two arms to assess the inflammatory status	daily up to day 15
Secondary	Free hemoglobin concentration	Investigators will assess the free hemoglobin concentrations in the two arms	daily up to day 15