Clinical trial NCT03266302: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infective Endocarditis
Keywords: vasodilatory shock
hemoadsorption
cardiac surgery
cytokines
Lead sponsor: Jena University Hospital
Sponsor class: OTHER
Collaborators: name: CytoSorbents, Inc
name: Thermo Fisher Scientific, Inc
name: Fraunhofer Institute for Interfacial Engineering and Biotechnology
name: German Federal Ministry of Education and Research
First posted: 2017-08-30
Enrollment: 288
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: two-arm randomized-controlled group sequential (Pocock) design for assessing superiority and safety
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: SOFA Score
timeFrame: 24 hours before until day 9 post-surgery
Secondary outcomes:
measure: Overall mortality rate
timeFrame: until day 30 post surgery
measure: Changes in cytokine and cfDNA levels
timeFrame: 24 hours before, during cardiac surgery and 24 hours after surgery
measure: SOFA subscores
timeFrame: 24 hours before surgery until day 9 post-surgery
measure: Days on ventilator, vasopressor and renal replacement therapy
timeFrame: until day 30 post-surgery
measure: incidence of stroke
timeFrame: until day 30 post-surgery
measure: length of ICU and in-hospital stay
timeFrame: until day 30 post-surgery
Other outcomes:
Locations:
city: Bad Krozingen
country: Germany
facility: University Heart Center Bad Krozingen
state: Baden-Württemberg
city: Freiburg
country: Germany
facility: University Heart Center Freiburg
state: Baden-Württemberg
city: Ulm
country: Germany
facility: University Hospital Ulm, Clinics of Heart-, Thoracic and Cardiovascular Surgery
state: Baden-Württemberg
city: Cologne
country: Germany
facility: University Hospital Cologne, Clinic and Policlinics for Heart and Thoracic Surgery
state: North Rhine-Westphalia
city: Essen
country: Germany
facility: University Hospital Essen, Clinic of Thoracic and Cardiovascular Surgery
state: North Rhine-Westphalia
city: Jena
country: Germany
facility: Jena University Hospital, Dept. of Cardiac and Thoracic Surgery
state: Thuringia
city: Bad Oeynhausen
country: Germany
facility: Herz- und Diabeteszentrum NRW, Klinik für Thorax- und Kardiovaskularchirurgie
city: Bernau bei Berlin
country: Germany
facility: Herzzentrum Brandenburg, Immanuel Klinikum Bernau
city: Bochum
country: Germany
facility: Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil gGmbH, Klinik für Herz- und Thoraxchirurgie
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn, Klinik und Poliklinik für Herzchirurgie
city: Dresden
country: Germany
facility: Herzzentrum Dresden GmbH, Universitätsklinik an der TU Dresden, Klinik für Herzchirurgie
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf, Klinik für Kardiovaskuläre Chirurgie
city: Halle (Saale)
country: Germany
facility: Mitteldeutsches Herzzentrum, Universitätsklinikum Halle (Saale), Universitätsklinik und Poliklinik für Herzchirurgie
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig, Universitätsklinik für Herzchirurgie
Study officials:
affiliation: Jena University Hospital, Department of Cardiac and Thoracic Surgery
name: Mahmoud Diab, Dr.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Brunkhorst FM, Oppert M, Marx G, Bloos F, Ludewig K, Putensen C, Nierhaus A, Jaschinski U, Meier-Hellmann A, Weyland A, Grundling M, Moerer O, Riessen R, Seibel A, Ragaller M, Buchler 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.
citation: Bustamante J, Arevalo 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.
citation: 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. doi: 10.1016/s0003-4975(96)01061-2.
citation: Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003 Jan 9;348(2):138-50. doi: 10.1056/NEJMra021333. No abstract available.
citation: 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.
citation: 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. No abstract available.
citation: Diab M, Lehmann T, Bothe W, Akhyari P, Platzer S, Wendt D, Deppe AC, Strauch J, Hagel S, Gunther A, Faerber G, Sponholz C, Franz M, Scherag A, Velichkov I, Silaschi M, Fassl J, Hofmann B, Lehmann S, Schramm R, Fritz G, Szabo G, Wahlers T, Matschke K, Lichtenberg A, Pletz MW, Gummert JF, Beyersdorf F, Hagl C, Borger MA, Bauer M, Brunkhorst FM, Doenst T; REMOVE Trial Investigators*. Cytokine Hemoadsorption During Cardiac Surgery Versus Standard Surgical Care for Infective Endocarditis (REMOVE): Results From a Multicenter Randomized Controlled Trial. Circulation. 2022 Mar 29;145(13):959-968. doi: 10.1161/CIRCULATIONAHA.121.056940. Epub 2022 Feb 25.
citation: 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.