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Cytokine REmoval in CRitically Ill pAtients Requiring Surgical Therapy for Infective Endocarditis (RECReATE) (RECREATE)

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ClinicalTrials.gov Identifier: NCT03892174
Recruitment Status : Recruiting
First Posted : March 27, 2019
Last Update Posted : November 26, 2019
Sponsor:
Information provided by (Responsible Party):
Jörg Schefold, University Hospital Inselspital, Berne

Brief Summary:
Infectious endocarditis (IE) and other severe infections are well-known to induce significant changes in the immune response including immune functionality in a considerable number of affected patients. In fact, numerous patients with IE develop a persistent functional immunological phenotype that can best be characterized by a profound anti-inflammation and/or functional anergy. This was previously referred to as "injury-associated immunosuppression (IAI)" by Pfortmüller et al., published in Intensive Care Medicine Experimental 2017. IAI can be assessed by measurement of cellular (functional) markers. Persistence of IAI is associated with prolonged ICU length of stay, increased secondary infection rates, and death. Immunomodulation to reverse IAI was shown beneficial in immunostimulatory (randomized controlled) clinical trials. CytoSorb® treatment is currently used as standard of care in some institutions in surgically treated IE patients. The investigators aim to investigate two accepted treatment protocols and aim to explore whether adsorption with a cytokine adsorption filter can increase immune competence in treated individuals.

Condition or disease Intervention/treatment Phase
Endocarditis Sepsis Septic Shock Other: Treatment protocol with adsorption Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Cytokine REmoval in CRitically Ill pAtients Requiring Surgical Therapy for Infective Endocarditis (RECReATE) - an Investigator-initiated Prospective Randomized Controlled Clinical Trial Comparing Two Established Clinical Protocols
Actual Study Start Date : November 14, 2019
Estimated Primary Completion Date : October 1, 2020
Estimated Study Completion Date : December 1, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Endocarditis

Arm Intervention/treatment
No Intervention: Treatment protocol without adsorption
Active Comparator: Treatment protocol with adsorption Other: Treatment protocol with adsorption
Adsorption while patients are in the OR on the extracorporeal circuit




Primary Outcome Measures :
  1. Change in quantitative expression of monocytic Human Leukocyte Antigen (mHLA)-DR expression (Antibodies per cell on Cluster of Differentiation (CD)14+ monocytes/macrophages, assessed using a quantitative standardized assay) [ Time Frame: From baseline (pre-OR, t1) to day 1 post-OR (t3) ]

Secondary Outcome Measures :
  1. Change in mHLA-DR from baseline (pre-OR) to post-Or and 3 days post-Or. [ Time Frame: Baseline (pre-OP) to post-OR and 3 days post-Or ]
    Course of mHLA-DR

  2. Area under the curve of quantitative mHLA-DR expression [ Time Frame: Between baseline (pre-OR), post-OR, and day 1 and 3 post-OR (multiple assessments). ]
    Area under the curves mHLA-DR

  3. Change in inflammatory markers including cytokines (Interleukin (IL)-6, IL-10, C-reactive protein, White blood cell count, multiplex Enzyme linked immunosorbent assay, and inflammatory prohormones) [ Time Frame: From baseline (pre-OR) to post-OR, and day 1 and 3 post-OR ]
    Change in inflammatory parameters

  4. Change in organ dysfunction (Sepsis-related organ failure (SOFA) scores incl. subscores and Simplified acute physiology score (SAPS II scores) daily [ Time Frame: 7-day timeframe (starting from ICu admission, assessed at day 90) ]
    Course of organ dysfunction

  5. Length of ICU and hospital stay (days after surgical intervention). [ Time Frame: Number of days on ICU and in hospital (assessed at day 90) ]
    Length of stay

  6. Cumulative Therapeutic Intervention Scoring System (TISS) points (resource need) until ICU-discharge [ Time Frame: Total number of TISS points on ICU (cumulative), assessed at day 90 ]
    Resource use

  7. Total amount of infused volume/transfusions on ICU [ Time Frame: 90 days ]
    Need for fluid therapy

  8. Duration of vasoactive drug therapy [ Time Frame: 90 days ]
    Vasopressor use

  9. Duration of invasive mechanical ventilation [ Time Frame: 90 days ]
    Use of organ support therapy (number of days on mechanical ventilation)

  10. ICU mortality rate [ Time Frame: ICU stay (assessed at day 90) ]
    Number of non-surviving patients in both study groups

  11. Hospital mortality rate [ Time Frame: hospital stay (assessed at day 90) ]
    Number of non-surviving patients in both study groups

  12. 28 day mortality rate [ Time Frame: 28 days beginning from ICU admission (assessed at day 90) ]
    Number of non-surviving patients in both study groups

  13. 90 day mortality rate [ Time Frame: 90 days beginning from ICU admission (assessed at day 90) ]
    Number of non-surviving patients in both study groups

  14. Duration of renal replacement therapy [ Time Frame: 90 days ]
    Use of organ support therapy (number of days on renal replacement therapy)



Information from the National Library of Medicine

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

Inclusion Criteria:

  • Subjects scheduled for routine cardiac surgery for infectious endocarditis (diagnosed according to the predefined "DUKE" criteria) with antibiotic therapy for ≤ 14 days.
  • Presence of informed consent
  • Age ≥18 yrs.

Exclusion Criteria:

  • Previous treatment (last 6 months) with immunologically-active biologicals or specific immunomodulatory drugs (e.g. Rituximab)
  • high-dose chronic (i.e. before onset of infectious endocarditis) steroid medication with prednisone equivalent of >30 mg/d
  • Patients on Extracorporeal membrane oxygenation (ECMO), or any other (pre-operative) cardiac assist device
  • Moribund patient (life expectancy <14 days)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03892174


Contacts
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Contact: Joerg C Schefold, MD 0041-31-632 ext 5397 joerg.schefold@insel.ch

Locations
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Switzerland
Dept of Intensive Care Medicine Recruiting
Bern, Switzerland, 3010
Contact: Joerg C Schefold, MD       joerg.schefold@insel.ch   
Contact: Lars Englberger, MD       lars.englberger@insel.ch   
Sponsors and Collaborators
University Hospital Inselspital, Berne
Investigators
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Study Director: Lars Englberger, MD Inselspital, Bern University Hospital

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Responsible Party: Jörg Schefold, Principal Investigator, University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier: NCT03892174    
Other Study ID Numbers: RECREATE
First Posted: March 27, 2019    Key Record Dates
Last Update Posted: November 26, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Endocarditis, Bacterial
Endocarditis
Infection
Heart Diseases
Cardiovascular Diseases
Bacterial Infections
Cardiovascular Infections