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

• ClinicalTrials.gov Identifier: NCT04157647
• Recruitment Status: Unknown
• First Posted: November 8, 2019
• Last Update Posted: November 12, 2020
• Sponsor: University Magna Graecia
• Information provided by (Responsible Party): GIUSEPPE FILIBERTO SERRAINO, University Magna Graecia

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Inflammatory Response; Chronic Renal Disease; Cardiac Surgery	Device: CytoSorb; Device: Control	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Prevention
• 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
• Estimated Study Start Date: November 15, 2020
• Estimated Primary Completion Date: November 1, 2021
• Estimated Study Completion Date: November 15, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. IL-6 concentration before cardiac surgery [ Time Frame: At day 0 before the cardiac surgery ]
   Investigators will assess the blood IL-6 concentrations between the two arms
2. IL-6 concentration at the end of CardioPulmonary Bypass [ Time Frame: At day 0 at the end of the CardioPulmonary Bypass ]
   Investigators will assess the blood IL-6 concentrations between the two arms
3. IL-6 concentration 2 hours after the end of CardioPulmonary Bypass [ Time Frame: 2 hours after the end of CardioPulmonary Bypass ]
   Investigators will assess the blood IL-6 concentrations between the two arms
4. IL-6 concentration 48 hours after the end of CardioPulmonary Bypass [ Time Frame: 48 hours after the end of CardioPulmonary Bypass ]
   Investigators will assess the blood IL-6 concentrations between the two arms
5. Renal function [ Time Frame: daily up to day 15 ]
   Investigators will assess the blood creatinine concentrations in the two arms
6. Myoglobin concentration [ Time Frame: daily up to day 15 ]
   Investigators will assess the blood myoglobin concentrations in the two arms
7. Haptoglobin concentration [ Time Frame: daily up to day 15 ]
   Investigators will assess the blood haptoglobin concentrations in the two arms
8. Liver transaminases concentration [ Time Frame: daily up to day 15 ]
   Investigators will measure the liver transaminases concentrations in the two arms to assess any liver injury
9. Osteopontin concentration [ Time Frame: daily up to day 15 ]
   Investigators will measure the osteopontin concentrations in the two arms to assess the inflammatory status
10. Free hemoglobin concentration [ Time Frame: daily up to day 15 ]
    Investigators will assess the free hemoglobin concentrations in the two arms

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Giuseppe F Serraino, MD; 0039 0961 3647033; filiberto@live.it

Locations

Italy

AOU Mater Domini

Catanzaro, CZ, Italy, 88100

Sponsors and Collaborators

University Magna Graecia

Investigators

• Principal Investigator: Giuseppe Serraino, MD; Magna Graecia University

More Information

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.

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.

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.

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.

• Responsible Party: GIUSEPPE FILIBERTO SERRAINO, Principal Investigator, University Magna Graecia
• ClinicalTrials.gov Identifier: NCT04157647
• Other Study ID Numbers: IMHeS
• First Posted: November 8, 2019
• Last Update Posted: November 12, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: The full protocol, datasets used and analysed during the current study will be available on reasonable request after study publication
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR); Analytic Code
• Time Frame: After scientific publication
• Access Criteria: On reasonable request

• 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

Keywords provided by GIUSEPPE FILIBERTO SERRAINO, University Magna Graecia:

hemadsorption

Additional relevant MeSH terms:

Renal Insufficiency, Chronic; Kidney Failure, Chronic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency; Chronic Disease; Disease Attributes; Pathologic Processes