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

Primary Purpose

Infective Endocarditis

Status
Completed
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
hemoadsorber for removal of cytokines
Sponsored by
Jena University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Infective Endocarditis focused on measuring vasodilatory shock, hemoadsorption, cardiac surgery, cytokines

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University Heart Center Bad Krozingen
  • University Heart Center Freiburg
  • University Hospital Ulm, Clinics of Heart-, Thoracic and Cardiovascular Surgery
  • University Hospital Cologne, Clinic and Policlinics for Heart and Thoracic Surgery
  • University Hospital Essen, Clinic of Thoracic and Cardiovascular Surgery
  • Jena University Hospital, Dept. of Cardiac and Thoracic Surgery
  • Herz- und Diabeteszentrum NRW, Klinik für Thorax- und Kardiovaskularchirurgie
  • Herzzentrum Brandenburg, Immanuel Klinikum Bernau
  • Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil gGmbH, Klinik für Herz- und Thoraxchirurgie
  • Universitätsklinikum Bonn, Klinik und Poliklinik für Herzchirurgie
  • Herzzentrum Dresden GmbH, Universitätsklinik an der TU Dresden, Klinik für Herzchirurgie
  • Universitätsklinikum Düsseldorf, Klinik für Kardiovaskuläre Chirurgie
  • Mitteldeutsches Herzzentrum, Universitätsklinikum Halle (Saale), Universitätsklinik und Poliklinik für Herzchirurgie
  • Herzzentrum Leipzig, Universitätsklinik für Herzchirurgie

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Interventional group

Control group

Arm Description

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)

Participants undergoing cardiac surgery due to infective endocarditis will be treated according to Standard of care (no hemoadsorption advice installed in the CPB circuit)

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Overall mortality rate
Overall mortality rate until day 30 post-surgery
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
SOFA subscores
single SOFA subscores will be analyzed
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
incidence of stroke
incidence of stroke within 30 days post-surgery will be assessed
length of ICU and in-hospital stay
total length of ICU and in-hospital stay until day 30 post-surgery

Full Information

First Posted
August 28, 2017
Last Updated
April 7, 2022
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
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1. Study Identification

Unique Protocol Identification Number
NCT03266302
Brief Title
Hemoadsorption for Prevention of Vasodilatory Shock in Cardiac Surgery Patients With Infective Endocarditis
Acronym
REMOVE
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

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
January 17, 2018 (Actual)
Primary Completion Date
February 28, 2020 (Actual)
Study Completion Date
December 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the 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

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infective Endocarditis
Keywords
vasodilatory shock, hemoadsorption, cardiac surgery, cytokines

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Sequential Assignment
Model Description
two-arm randomized-controlled group sequential (Pocock) design for assessing superiority and safety
Masking
Participant
Masking Description
Participant will not be informed about group allocation
Allocation
Randomized
Enrollment
288 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Interventional group
Arm Type
Experimental
Arm Description
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)
Arm Title
Control group
Arm Type
No Intervention
Arm Description
Participants undergoing cardiac surgery due to infective endocarditis will be treated according to Standard of care (no hemoadsorption advice installed in the CPB circuit)
Intervention Type
Device
Intervention Name(s)
hemoadsorber for removal of cytokines
Other Intervention Name(s)
CytoSorb(R)
Intervention Description
Use of the hemoadsorber during cardiac surgery with CPB. Hemoadsorber is integrated into the CPB circuit according to manufacturer's recommendation.
Primary Outcome Measure Information:
Title
SOFA Score
Description
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 Outcome Measure Information:
Title
Overall mortality rate
Description
Overall mortality rate until day 30 post-surgery
Time Frame
until day 30 post surgery
Title
Changes in cytokine and cfDNA levels
Description
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
Title
SOFA subscores
Description
single SOFA subscores will be analyzed
Time Frame
24 hours before surgery until day 9 post-surgery
Title
Days on ventilator, vasopressor and renal replacement therapy
Description
Total days on ventilator, vasopressor and renal replacement therapy within 30 days post-surgery will be assessed
Time Frame
until day 30 post-surgery
Title
incidence of stroke
Description
incidence of stroke within 30 days post-surgery will be assessed
Time Frame
until day 30 post-surgery
Title
length of ICU and in-hospital stay
Description
total length of ICU and in-hospital stay until day 30 post-surgery
Time Frame
until day 30 post-surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mahmoud Diab, Dr.
Organizational Affiliation
Jena University Hospital, Department of Cardiac and Thoracic Surgery
Official's Role
Study Director
Facility Information:
Facility Name
University Heart Center Bad Krozingen
City
Bad Krozingen
State/Province
Baden-Württemberg
ZIP/Postal Code
D-79189
Country
Germany
Facility Name
University Heart Center Freiburg
City
Freiburg
State/Province
Baden-Württemberg
ZIP/Postal Code
D-79106
Country
Germany
Facility Name
University Hospital Ulm, Clinics of Heart-, Thoracic and Cardiovascular Surgery
City
Ulm
State/Province
Baden-Württemberg
ZIP/Postal Code
D-89081
Country
Germany
Facility Name
University Hospital Cologne, Clinic and Policlinics for Heart and Thoracic Surgery
City
Cologne
State/Province
North Rhine-Westphalia
ZIP/Postal Code
D-50937
Country
Germany
Facility Name
University Hospital Essen, Clinic of Thoracic and Cardiovascular Surgery
City
Essen
State/Province
North Rhine-Westphalia
ZIP/Postal Code
D-45147
Country
Germany
Facility Name
Jena University Hospital, Dept. of Cardiac and Thoracic Surgery
City
Jena
State/Province
Thuringia
ZIP/Postal Code
07747
Country
Germany
Facility Name
Herz- und Diabeteszentrum NRW, Klinik für Thorax- und Kardiovaskularchirurgie
City
Bad Oeynhausen
ZIP/Postal Code
32545
Country
Germany
Facility Name
Herzzentrum Brandenburg, Immanuel Klinikum Bernau
City
Bernau bei Berlin
ZIP/Postal Code
16321
Country
Germany
Facility Name
Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil gGmbH, Klinik für Herz- und Thoraxchirurgie
City
Bochum
ZIP/Postal Code
44789
Country
Germany
Facility Name
Universitätsklinikum Bonn, Klinik und Poliklinik für Herzchirurgie
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Facility Name
Herzzentrum Dresden GmbH, Universitätsklinik an der TU Dresden, Klinik für Herzchirurgie
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Universitätsklinikum Düsseldorf, Klinik für Kardiovaskuläre Chirurgie
City
Düsseldorf
ZIP/Postal Code
40225
Country
Germany
Facility Name
Mitteldeutsches Herzzentrum, Universitätsklinikum Halle (Saale), Universitätsklinik und Poliklinik für Herzchirurgie
City
Halle (Saale)
ZIP/Postal Code
06120
Country
Germany
Facility Name
Herzzentrum Leipzig, Universitätsklinik für Herzchirurgie
City
Leipzig
ZIP/Postal Code
04289
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
27059056
Citation
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Results Reference
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Citation
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Citation
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Citation
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Results Reference
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PubMed Identifier
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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.
Results Reference
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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.
Results Reference
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35213213
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.
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Citation
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Results Reference
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Hemoadsorption for Prevention of Vasodilatory Shock in Cardiac Surgery Patients With Infective Endocarditis

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