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CompletedNCT03266302REMOVEUpdated Mar 18, 2025

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

An interventional study of hemoadsorber for removal of cytokines in Infective Endocarditis, sponsored by Jena University Hospital. Completed at 14 sites in Germany. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-03-18.

Sponsored by Jena University Hospital · Not applicable, Interventional, and Prevention

Phase
Not applicable
Study type
Interventional
Enrollment
288
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Infective Endocarditis

Keywords

  • vasodilatory shock
  • hemoadsorption
  • cardiac surgery
  • cytokines
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

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

Exclusion criteria

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
04

Study design

Phase
Not applicable
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Sequential assignment
Masking
Single (Participant)
Enrollment
288 participants (actual)

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)

    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)

Interventions

  • Devicehemoadsorber 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.

    Also known as: CytoSorb(R)

05

What researchers measure

Primary outcomes

  1. SOFA Score

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

    Time frame: 24 hours before until day 9 post-surgery

Secondary outcomes

  1. Overall mortality rate

    Overall mortality rate until day 30 post-surgery

    Time frame: until day 30 post surgery

  2. Changes in cytokine and cfDNA levels

    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

    Time frame: 24 hours before, during cardiac surgery and 24 hours after surgery

  3. SOFA subscores

    single SOFA subscores will be analyzed

    Time frame: 24 hours before surgery until day 9 post-surgery

  4. Days on ventilator, vasopressor and renal replacement therapy

    Total days on ventilator, vasopressor and renal replacement therapy within 30 days post-surgery will be assessed

    Time frame: until day 30 post-surgery

  5. incidence of stroke

    incidence of stroke within 30 days post-surgery will be assessed

    Time frame: until day 30 post-surgery

  6. length of ICU and in-hospital stay

    total length of ICU and in-hospital stay until day 30 post-surgery

    Time frame: until day 30 post-surgery

06

Study locations

14 sites
  • University Heart Center Bad Krozingen
    Bad Krozingen, Baden-Württemberg D-79189, Germany
  • University Heart Center Freiburg
    Freiburg, Baden-Württemberg D-79106, Germany
  • University Hospital Ulm, Clinics of Heart-, Thoracic and Cardiovascular Surgery
    Ulm, Baden-Württemberg D-89081, Germany
  • University Hospital Cologne, Clinic and Policlinics for Heart and Thoracic Surgery
    Cologne, North Rhine-Westphalia D-50937, Germany
  • University Hospital Essen, Clinic of Thoracic and Cardiovascular Surgery
    Essen, North Rhine-Westphalia D-45147, Germany
  • Jena University Hospital, Dept. of Cardiac and Thoracic Surgery
    Jena, Thuringia 07747, Germany
  • Herz- und Diabeteszentrum NRW, Klinik für Thorax- und Kardiovaskularchirurgie
    Bad Oeynhausen, 32545, Germany
  • Herzzentrum Brandenburg, Immanuel Klinikum Bernau
    Bernau bei Berlin, 16321, Germany
  • Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil gGmbH, Klinik für Herz- und Thoraxchirurgie
    Bochum, 44789, Germany
  • Universitätsklinikum Bonn, Klinik und Poliklinik für Herzchirurgie
    Bonn, 53127, Germany
  • Herzzentrum Dresden GmbH, Universitätsklinik an der TU Dresden, Klinik für Herzchirurgie
    Dresden, 01307, Germany
  • Universitätsklinikum Düsseldorf, Klinik für Kardiovaskuläre Chirurgie
    Düsseldorf, 40225, Germany
  • Mitteldeutsches Herzzentrum, Universitätsklinikum Halle (Saale), Universitätsklinik und Poliklinik für Herzchirurgie
    Halle (Saale), 06120, Germany
  • Herzzentrum Leipzig, Universitätsklinik für Herzchirurgie
    Leipzig, 04289, Germany
07

References and documents

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. PubMed 27059056 ↗
  • 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. PubMed 22692171 ↗
  • 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. PubMed 24106887 ↗
  • 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. PubMed 8993292 ↗
  • 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. PubMed 12519925 ↗
  • 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. PubMed 19091120 ↗
  • 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. PubMed 20212293 ↗
  • 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. PubMed 35213213 ↗
  • 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. PubMed 32234739 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03266302
Lead sponsor
Jena University Hospital
Collaborators
CytoSorbents, Inc, Thermo Fisher Scientific, Inc, Fraunhofer Institute for Interfacial Engineering and Biotechnology, German Federal Ministry of Education and Research
Responsible party
Sponsor
First posted
Aug 30, 2017
Start date
Jan 17, 2018
Primary completion
Feb 28, 2020
Completion
Dec 31, 2020
Last update
Mar 18, 2025

Study contacts

Mahmoud Diab, Dr.
study director · Jena University Hospital, Department of Cardiac and Thoracic Surgery

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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