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

Tracking Information

• First Submitted Date: August 28, 2017
• First Posted Date: August 30, 2017
• Last Update Posted Date: March 4, 2020
• Actual Study Start Date: January 17, 2018
• Actual Primary Completion Date: February 28, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 30, 2017)

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.

Original Primary Outcome Measures (submitted: August 29, 2017)

SOFA Score [ Time Frame: 24 hours before until day 9 post-surgery ]

We will test if mean SOFA scores are different for the experimental and control group.

Current Secondary Outcome Measures (submitted: August 29, 2017)

• Overall mortality rate [ Time Frame: until day 30 post surgery ]
  Overall mortality rate until day 30 post-surgery
• 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
• SOFA subscores [ Time Frame: 24 hours before surgery until day 9 post-surgery ]
  single SOFA subscores will be analyzed
• 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
• incidence of stroke [ Time Frame: until day 30 post-surgery ]
  incidence of stroke within 30 days post-surgery will be assessed
• 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Hemoadsorption for Prevention of Vasodilatory Shock in Cardiac Surgery Patients With Infective Endocarditis
• 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
• 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.
• 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 Type: Interventional
• Study Phase: Not Applicable

Study Design

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

• Condition: Infective Endocarditis

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)

Study Arms

• 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)
  Intervention: Device: hemoadsorber for removal of cytokines
• 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)

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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 3, 2020): 288
• Original Estimated Enrollment (submitted: August 29, 2017): 250
• Actual Study Completion Date: February 28, 2020
• Actual Primary Completion Date: February 28, 2020 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT03266302
• Other Study ID Numbers: ZKSJ0108
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Jena University Hospital
• Study Sponsor: Jena University Hospital

Collaborators

• 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

• PRS Account: Jena University Hospital
• Verification Date: March 2020