Hemadsorption During and After Cardiopulmonary Bypass to Modulate the Inflammatory Response (IMHeS)

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.

Study Overview

• Status: Unknown
• Conditions: Inflammatory Response; Cardiac Surgery; Chronic Renal Disease
• Intervention / Treatment: Device: CytoSorb; Device: Control

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • CZ
    • Catanzaro, CZ, Italy, 88100
      • AOU Mater Domini

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CytoSorb; Patients assigned to this arm group will receive hemadsorption witbhCytoSorb during the surgery and in the next 24 hours after surgery.	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.
Sham Comparator: Control; Patients assigned to this arm group will undergo to a normal CPB without the use of any hemoadsorption system.	Device: Control; No hemadsorption filter or other treatment will be included in the CPB circuit

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IL-6 concentration at ICU admission	Investigators will assess the blood IL-6 concentrations between the two arms	At day 0 after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
Renal function	Investigators will assess the blood creatinine concentrations in the two arms	daily up to day 15
Myoglobin concentration	Investigators will assess the blood myoglobin concentrations in the two arms	daily up to day 15
Haptoglobin concentration	Investigators will assess the blood haptoglobin concentrations in the two arms	daily up to day 15
Liver transaminases concentration	Investigators will measure the liver transaminases concentrations in the two arms to assess any liver injury	daily up to day 15
Osteopontin concentration	Investigators will measure the osteopontin concentrations in the two arms to assess the inflammatory status	daily up to day 15
Free hemoglobin concentration	Investigators will assess the free hemoglobin concentrations in the two arms	daily up to day 15

Collaborators and Investigators

• Sponsor: University Magna Graecia
• Investigators: Principal Investigator: Giuseppe Serraino, MD, Magna Graecia University

Publications and helpful links

General Publications

• 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.
• 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.
• 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. doi: 10.1016/s0003-4975(02)03711-6.
• Durmaz 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.
• Pecoits-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.
• 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. doi: 10.1081/jdi-100100878.
• 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. doi: 10.1111/j.1523-1755.2002.kid556.x.
• Corral-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.
• 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.
• Ilmakunnas 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.
• 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. No abstract available.
• Hetz 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): November 15, 2020
• Primary Completion (Anticipated): November 1, 2021
• Study Completion (Anticipated): November 15, 2021

Study Registration Dates

• First Submitted: October 13, 2019
• First Submitted That Met QC Criteria: November 7, 2019
• First Posted (Actual): November 8, 2019

Study Record Updates

• Last Update Posted (Actual): November 12, 2020
• Last Update Submitted That Met QC Criteria: November 10, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: hemadsorption
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Failure, Chronic
• Other Study ID Numbers: IMHeS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The full protocol, datasets used and analysed during the current study will be available on reasonable request after study publication
• IPD Sharing Time Frame: After scientific publication
• IPD Sharing Access Criteria: On reasonable request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No