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

Primary Purpose

Endocarditis, Sepsis, Septic Shock

Status

Recruiting

Phase

Not Applicable

Locations

Switzerland

Study Type

Interventional

Intervention

Treatment protocol with adsorption

About this trial

This is an interventional treatment trial for Endocarditis

Eligibility Criteria

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

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)

Sites / Locations

Dept of Intensive Care MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Active Comparator

Arm Label

Treatment protocol without adsorption

Treatment protocol with adsorption

Arm Description

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Change in mHLA-DR from baseline (pre-OR) to post-Or and 3 days post-Or.

Course of mHLA-DR

Area under the curve of quantitative mHLA-DR expression

Area under the curves mHLA-DR

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)

Change in inflammatory parameters

Change in organ dysfunction (Sepsis-related organ failure (SOFA) scores incl. subscores and Simplified acute physiology score (SAPS II scores) daily

Course of organ dysfunction

Length of ICU and hospital stay (days after surgical intervention).

Length of stay

Cumulative Therapeutic Intervention Scoring System (TISS) points (resource need) until ICU-discharge

Resource use

Total amount of infused volume/transfusions on ICU

Need for fluid therapy

Duration of vasoactive drug therapy

Vasopressor use

Duration of invasive mechanical ventilation

Use of organ support therapy (number of days on mechanical ventilation)

ICU mortality rate

Number of non-surviving patients in both study groups

Hospital mortality rate

Number of non-surviving patients in both study groups

28 day mortality rate

Number of non-surviving patients in both study groups

90 day mortality rate

Number of non-surviving patients in both study groups

Duration of renal replacement therapy

Use of organ support therapy (number of days on renal replacement therapy)

Full Information

NCT ID

NCT03892174

First Posted

March 22, 2019

Last Updated

January 25, 2023

Sponsor

Insel Gruppe AG, University Hospital Bern

1. Study Identification

Unique Protocol Identification Number

NCT03892174

Brief Title

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

Acronym

RECREATE

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 14, 2019 (Actual)

Primary Completion Date

October 1, 2024 (Anticipated)

Study Completion Date

December 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Insel Gruppe AG, University Hospital Bern

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Endocarditis, Sepsis, Septic Shock

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

54 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment protocol without adsorption

Arm Type

No Intervention

Arm Title

Treatment protocol with adsorption

Arm Type

Active Comparator

Intervention Type

Other

Intervention Name(s)

Treatment protocol with adsorption

Intervention Description

Adsorption while patients are in the OR on the extracorporeal circuit

Primary Outcome Measure Information:

Title

Time Frame

From baseline (pre-OR, t1) to day 1 post-OR (t3)

Secondary Outcome Measure Information:

Title

Change in mHLA-DR from baseline (pre-OR) to post-Or and 3 days post-Or.

Description

Course of mHLA-DR

Time Frame

Baseline (pre-OP) to post-OR and 3 days post-Or

Title

Area under the curve of quantitative mHLA-DR expression

Description

Area under the curves mHLA-DR

Time Frame

Between baseline (pre-OR), post-OR, and day 1 and 3 post-OR (multiple assessments).

Title

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)

Description

Change in inflammatory parameters

Time Frame

From baseline (pre-OR) to post-OR, and day 1 and 3 post-OR

Title

Change in organ dysfunction (Sepsis-related organ failure (SOFA) scores incl. subscores and Simplified acute physiology score (SAPS II scores) daily

Description

Course of organ dysfunction

Time Frame

7-day timeframe (starting from ICu admission, assessed at day 90)

Title

Length of ICU and hospital stay (days after surgical intervention).

Description

Length of stay

Time Frame

Number of days on ICU and in hospital (assessed at day 90)

Title

Cumulative Therapeutic Intervention Scoring System (TISS) points (resource need) until ICU-discharge

Description

Resource use

Time Frame

Total number of TISS points on ICU (cumulative), assessed at day 90

Title

Total amount of infused volume/transfusions on ICU

Description

Need for fluid therapy

Time Frame

90 days

Title

Duration of vasoactive drug therapy

Description

Vasopressor use

Time Frame

90 days

Title

Duration of invasive mechanical ventilation

Description

Use of organ support therapy (number of days on mechanical ventilation)

Time Frame

90 days

Title

ICU mortality rate

Description

Number of non-surviving patients in both study groups

Time Frame

ICU stay (assessed at day 90)

Title

Hospital mortality rate

Description

Number of non-surviving patients in both study groups

Time Frame

hospital stay (assessed at day 90)

Title

28 day mortality rate

Description

Number of non-surviving patients in both study groups

Time Frame

28 days beginning from ICU admission (assessed at day 90)

Title

90 day mortality rate

Description

Number of non-surviving patients in both study groups

Time Frame

90 days beginning from ICU admission (assessed at day 90)

Title

Duration of renal replacement therapy

Description

Use of organ support therapy (number of days on renal replacement therapy)

Time Frame

90 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Joerg C Schefold, MD

Phone

0041-31-632

Ext

5397

joerg.schefold@insel.ch

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lars Englberger, MD

Organizational Affiliation

Inselspital, Bern University Hospital

Official's Role

Study Director

Facility Information:

Facility Name

Dept of Intensive Care Medicine

City

Bern

ZIP/Postal Code

3010

Country

Switzerland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Joerg C Schefold, MD

joerg.schefold@insel.ch

First Name & Middle Initial & Last Name & Degree

Lars Englberger, MD

lars.englberger@insel.ch

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

32282706

Citation

Gisler F, Spinetti T, Erdoes G, Luedi MM, Pfortmueller CA, Messmer AS, Jenni H, Englberger L, Schefold JC. 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. Medicine (Baltimore). 2020 Apr;99(15):e19580. doi: 10.1097/MD.0000000000019580.

Results Reference

derived

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

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