Hemoadsorption for Prevention of Vasodilatory Shock in Cardiac Surgery Patients With Infective Endocarditis (REMOVE)

• ClinicalTrials.gov Identifier: NCT03266302
• Recruitment Status: Completed
• First Posted: August 30, 2017
• Last Update Posted: March 4, 2020
• Sponsor: Jena University Hospital
• Collaborators: CytoSorbents, Inc; Thermo Fisher Scientific; Fraunhofer Institute for Interfacial Engineering and Biotechnology; German Federal Ministry of Education and Research
• Information provided by (Responsible Party): Jena University Hospital

Study Description

Brief Summary:

Infective endocarditis (IE) is associated with high hospital mortality for various reasons; one of them is circulatory failure in patients who undergo cardiac surgery for IE. One discussed reason underlying circulatory failure during surgery is the release of vasodilatatory mediators and cytokines. This study examines the efficacy and safety of a hemoadsorption filter which is approved for the reduction of the concentration of cytokines in the bloodstream.

Condition or disease	Intervention/treatment	Phase
Infective Endocarditis	Device: hemoadsorber for removal of cytokines	Not Applicable

Detailed Description:

The investigators assume a common standard deviation of 3.8 points and that a 1.4-point lower SOFA score in the Intervention Group is of clinical relevance.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 288 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: two-arm randomized-controlled group sequential (Pocock) design for assessing superiority and safety
• Masking: Single (Participant)
• Masking Description: Participant will not be informed about group allocation
• Primary Purpose: Prevention
• Official Title: Revealing Mechanisms and Investigating Efficacy of Hemoadsorption for Prevention of Vasodilatory Shock in Cardiac Surgery Patients With Infective Endocarditis - a Multicentric Randomized Controlled Group Sequential Trial
• Actual Study Start Date: January 17, 2018
• Actual Primary Completion Date: February 28, 2020
• Actual Study Completion Date: February 28, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Interventional group; Use of hemoadsorber for removal of cytokines. Participants undergoing cardiac surgery due to infective endocarditis will be treated using a hemoadsorption device (CytoSorb) within the cardiopulmonary Bypass circuit (=Intervention)	Device: hemoadsorber for removal of cytokines; Use of the hemoadsorber during cardiac surgery with CPB. Hemoadsorber is integrated into the CPB circuit according to manufacturer's recommendation.; Other Name: CytoSorb(R)
No Intervention: Control group; Participants undergoing cardiac surgery due to infective endocarditis will be treated according to Standard of care (no hemoadsorption advice installed in the CPB circuit)

Outcome Measures

Primary Outcome Measures :

1. SOFA Score [ Time Frame: 24 hours before until day 9 post-surgery ]
   The investigators will test if mean SOFA scores are different for the experimental and control group.

Secondary Outcome Measures :

1. Overall mortality rate [ Time Frame: until day 30 post surgery ]
   Overall mortality rate until day 30 post-surgery
2. Changes in cytokine and cfDNA levels [ Time Frame: 24 hours before, during cardiac surgery and 24 hours after surgery ]
   changes in cytokine and cfDNA levels will be measured at different time points before, during and after surgery in both groups; only for the first 2x25 patients
3. SOFA subscores [ Time Frame: 24 hours before surgery until day 9 post-surgery ]
   single SOFA subscores will be analyzed
4. Days on ventilator, vasopressor and renal replacement therapy [ Time Frame: until day 30 post-surgery ]
   Total days on ventilator, vasopressor and renal replacement therapy within 30 days post-surgery will be assessed
5. incidence of stroke [ Time Frame: until day 30 post-surgery ]
   incidence of stroke within 30 days post-surgery will be assessed
6. length of ICU and in-hospital stay [ Time Frame: until day 30 post-surgery ]
   total length of ICU and in-hospital stay until day 30 post-surgery

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• patients with infective endocarditis (according to DUKE criteria) undergoing cardiac surgery
• informed consent
• age ≥18 years

Exclusion Criteria:

• EuroScoreII ≤ 3
• current participation in another interventional Trial
• pregnancy
• current immunosuppressive or immunomodulatory therapy (with dosing of glucocorticoids over Cushing threshold)
• previous participation in the REMOVE study

Contacts and Locations

Locations

Germany

University Heart Center Bad Krozingen

Bad Krozingen, Baden-Württemberg, Germany, D-79189

University Heart Center Freiburg

Freiburg, Baden-Württemberg, Germany, D-79106

University Hospital Ulm, Clinics of Heart-, Thoracic and Cardiovascular Surgery

Ulm, Baden-Württemberg, Germany, D-89081

University Hospital Cologne, Clinic and Policlinics for Heart and Thoracic Surgery

Cologne, North Rhine-Westphalia, Germany, D-50937

University Hospital Essen, Clinic of Thoracic and Cardiovascular Surgery

Essen, North Rhine-Westphalia, Germany, D-45147

Jena University Hospital, Dept. of Cardiac and Thoracic Surgery

Jena, Thuringia, Germany, 07747

Herz- und Diabeteszentrum NRW, Klinik für Thorax- und Kardiovaskularchirurgie

Bad Oeynhausen, Germany, 32545

Herzzentrum Brandenburg, Immanuel Klinikum Bernau

Bernau bei Berlin, Germany, 16321

Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil gGmbH, Klinik für Herz- und Thoraxchirurgie

Bochum, Germany, 44789

Universitätsklinikum Bonn, Klinik und Poliklinik für Herzchirurgie

Bonn, Germany, 53127

Herzzentrum Dresden GmbH, Universitätsklinik an der TU Dresden, Klinik für Herzchirurgie

Dresden, Germany, 01307

Universitätsklinikum Düsseldorf, Klinik für Kardiovaskuläre Chirurgie

Düsseldorf, Germany, 40225

Mitteldeutsches Herzzentrum, Universitätsklinikum Halle (Saale), Universitätsklinik und Poliklinik für Herzchirurgie

Halle (Saale), Germany, 06120

Herzzentrum Leipzig, Universitätsklinik für Herzchirurgie

Leipzig, Germany, 04289

Sponsors and Collaborators

Jena University Hospital

CytoSorbents, Inc

Thermo Fisher Scientific

Fraunhofer Institute for Interfacial Engineering and Biotechnology

German Federal Ministry of Education and Research

Investigators

• Study Director: Mahmoud Diab, Dr.; Jena University Hospital, Department of Cardiac and Thoracic Surgery

More Information

Publications:

Bernardi MH, Rinoesl H, Dragosits K, Ristl R, Hoffelner F, Opfermann P, Lamm C, Preißing F, Wiedemann D, Hiesmayr MJ, Spittler A. Effect of hemoadsorption during cardiopulmonary bypass surgery - a blinded, randomized, controlled pilot study using a novel adsorbent. Crit Care. 2016 Apr 9;20:96. doi: 10.1186/s13054-016-1270-0.

Brunkhorst FM, Oppert M, Marx G, Bloos F, Ludewig K, Putensen C, Nierhaus A, Jaschinski U, Meier-Hellmann A, Weyland A, Gründling M, Moerer O, Riessen R, Seibel A, Ragaller M, Büchler MW, John S, Bach F, Spies C, Reill L, Fritz H, Kiehntopf M, Kuhnt E, Bogatsch H, Engel C, Loeffler M, Kollef MH, Reinhart K, Welte T; German Study Group Competence Network Sepsis (SepNet). Effect of empirical treatment with moxifloxacin and meropenem vs meropenem on sepsis-related organ dysfunction in patients with severe sepsis: a randomized trial. JAMA. 2012 Jun 13;307(22):2390-9. doi: 10.1001/jama.2012.5833.

Bustamante J, Arévalo A, Tamayo E, Sarria C, Aguilar-Blanco EM, Heredia M, Almansa R, Rico L, Iglesias V, Bermejo-Martin JF. Cytokine profiles linked to fatal outcome in infective prosthetic valve endocarditis. APMIS. 2014 Jun;122(6):526-9. doi: 10.1111/apm.12189. Epub 2013 Sep 30.

Boyle EM Jr, Pohlman TH, Johnson MC, Verrier ED. Endothelial cell injury in cardiovascular surgery: the systemic inflammatory response. Ann Thorac Surg. 1997 Jan;63(1):277-84. Review.

Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003 Jan 9;348(2):138-50. Review.

Minne L, Abu-Hanna A, de Jonge E. Evaluation of SOFA-based models for predicting mortality in the ICU: A systematic review. Crit Care. 2008;12(6):R161. doi: 10.1186/cc7160. Epub 2008 Dec 17. Review.

Prendergast BD, Tornos P. Surgery for infective endocarditis: who and when? Circulation. 2010 Mar 9;121(9):1141-52. doi: 10.1161/CIRCULATIONAHA.108.773598. Review.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Diab M, Platzer S, Guenther A, Sponholz C, Scherag A, Lehmann T, Velichkov I, Hagel S, Bauer M, Brunkhorst FM, Doenst T. Assessing efficacy of CytoSorb haemoadsorber for prevention of organ dysfunction in cardiac surgery patients with infective endocarditis: REMOVE-protocol for randomised controlled trial. BMJ Open. 2020 Mar 30;10(3):e031912. doi: 10.1136/bmjopen-2019-031912.

• Responsible Party: Jena University Hospital
• ClinicalTrials.gov Identifier: NCT03266302
• Other Study ID Numbers: ZKSJ0108
• First Posted: August 30, 2017
• Last Update Posted: March 4, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jena University Hospital:

vasodilatory shock; hemoadsorption; cardiac surgery; cytokines

Additional relevant MeSH terms:

Endocarditis, Bacterial; Endocarditis; Heart Diseases; Cardiovascular Diseases; Bacterial Infections; Cardiovascular Infections; Infection