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

• ClinicalTrials.gov Identifier: NCT04157647
• Recruitment Status: Not yet recruiting
• 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

Tracking Information

• First Submitted Date: October 13, 2019
• First Posted Date: November 8, 2019
• Last Update Posted Date: November 12, 2020
• Estimated Study Start Date: November 15, 2020
• Estimated Primary Completion Date: November 1, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 7, 2019)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 7, 2019)

• 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
• 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
• 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
• 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
• Renal function [ Time Frame: daily up to day 15 ]
  Investigators will assess the blood creatinine concentrations in the two arms
• Myoglobin concentration [ Time Frame: daily up to day 15 ]
  Investigators will assess the blood myoglobin concentrations in the two arms
• Haptoglobin concentration [ Time Frame: daily up to day 15 ]
  Investigators will assess the blood haptoglobin concentrations in the two arms
• 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
• Osteopontin concentration [ Time Frame: daily up to day 15 ]
  Investigators will measure the osteopontin concentrations in the two arms to assess the inflammatory status
• Free hemoglobin concentration [ Time Frame: daily up to day 15 ]
  Investigators will assess the free hemoglobin concentrations in the two arms

Original Secondary Outcome Measures (submitted: November 7, 2019)

• IL-6 concentration before cardiac surgery [ Time Frame: The morning before the cardiac surgery ]
  Investigators will assess the blood IL-6 concentrations between the two arms
• IL-6 concentration at the end of CardioPulmonary Bypass [ Time Frame: At the end of the CardioPulmonary Bypass ]
  Investigators will assess the blood IL-6 concentrations between the two arms
• 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
• 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
• Renal function [ Time Frame: daily up to day 15 ]
  Investigators will assess the blood creatinine concentrations in the two arms
• Myoglobin concentration [ Time Frame: daily up to day 15 ]
  Investigators will assess the blood myoglobin concentrations in the two arms
• Haptoglobin concentration [ Time Frame: daily up to day 15 ]
  Investigators will assess the blood haptoglobin concentrations in the two arms
• 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
• Osteopontin concentration [ Time Frame: daily up to day 15 ]
  Investigators will measure the osteopontin concentrations in the two arms to assess the inflammatory status
• Free hemoglobin concentration [ Time Frame: daily up to day 15 ]
  Investigators will assess the free hemoglobin concentrations in the two arms

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Hemadsorption During and After Cardiopulmonary Bypass to Modulate the Inflammatory Response
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Outcomes Assessor); Primary Purpose: Prevention

Condition

• Inflammatory Response
• Chronic Renal Disease
• Cardiac Surgery

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

Study Arms

• Active Comparator: CytoSorb
  Patients assigned to this arm group will receive hemadsorption witbhCytoSorb during the surgery and in the next 24 hours after surgery.
  Intervention: Device: CytoSorb
• Sham Comparator: Control
  Patients assigned to this arm group will undergo to a normal CPB without the use of any hemoadsorption system.
  Intervention: Device: Control

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. Epub 2006 May 31. Review.
• 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.
• Durmaz I, Büket S, Atay Y, Yağdi T, Ozbaran M, Boğa M, Alat I, Güzelant A, Başarir S. Cardiac surgery with cardiopulmonary bypass in patients with chronic renal failure. J Thorac Cardiovasc Surg. 1999 Aug;118(2):306-15.
• 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.
• 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.
• 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.
• 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.
• 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, 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.
• 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.
• 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 β-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. Review.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: November 7, 2019): 40
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 15, 2021
• Estimated Primary Completion Date: November 1, 2021 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 65 Years and older (Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT04157647
• Other Study ID Numbers: IMHeS
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

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
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code
• Time Frame: After scientific publication
• Access Criteria: On reasonable request

• Responsible Party: GIUSEPPE FILIBERTO SERRAINO, University Magna Graecia
• Study Sponsor: University Magna Graecia
• Collaborators: Not Provided

Investigators

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

• PRS Account: University Magna Graecia
• Verification Date: November 2020