EndocarditisRECREATENCT03892174
Cytokine REmoval in CRitically Ill PAtients Requiring Surgical Therapy for Infective Endocarditis (RECReATE)
A study testing Treatment protocol with adsorption in people with Endocarditis and Sepsis, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Endocarditis, Sepsis, Septic Shock
- What is being tested?
- Treatment protocol with adsorption
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteSwitzerland
- Study dates
- 14 Nov 2019to 31 Dec 2024
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland1 site, 1 recruiting
- Recruiting
Dept of Intensive Care Medicine
Bern, 3010
Joerg C Schefold, MD, joerg.schefold@insel.ch
Lars Englberger, MD, lars.englberger@insel.ch
About this study
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
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.
- Conditions
- Endocarditis, Sepsis, Septic Shock
- Being tested
- Treatment protocol with adsorption
- Medical subject headings
- Endocarditis, Sepsis, Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Treatment protocol with adsorptionOther
Adsorption while patients are in the OR on the extracorporeal circuit
| Study group | Role | What they receive |
|---|---|---|
| Treatment protocol without adsorption | No intervention | Not described |
| Treatment protocol with adsorption | Active comparator | Not described Receives: Other: Treatment protocol with adsorption |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: From baseline (pre-OR, t1) to day 1 post-OR (t3)
Secondary outcomes (14)
Change in mHLA-DR from baseline (pre-OR) to post-Or and 3 days post-Or.
Course of mHLA-DR
Measured: Baseline (pre-OP) to post-OR and 3 days post-Or
Area under the curve of quantitative mHLA-DR expression
Area under the curves mHLA-DR
Measured: Between baseline (pre-OR), post-OR, and day 1 and 3 post-OR (multiple assessments).
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
Measured: From baseline (pre-OR) to post-OR, and day 1 and 3 post-OR
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
Measured: 7-day timeframe (starting from ICu admission, assessed at day 90)
Length of ICU and hospital stay (days after surgical intervention).
Length of stay
Measured: Number of days on ICU and in hospital (assessed at day 90)
Cumulative Therapeutic Intervention Scoring System (TISS) points (resource need) until ICU-discharge
Resource use
Measured: Total number of TISS points on ICU (cumulative), assessed at day 90
Total amount of infused volume/transfusions on ICU
Need for fluid therapy
Measured: 90 days
Duration of vasoactive drug therapy
Vasopressor use
Measured: 90 days
Duration of invasive mechanical ventilation
Use of organ support therapy (number of days on mechanical ventilation)
Measured: 90 days
ICU mortality rate
Number of non-surviving patients in both study groups
Measured: ICU stay (assessed at day 90)
Hospital mortality rate
Number of non-surviving patients in both study groups
Measured: hospital stay (assessed at day 90)
28 day mortality rate
Number of non-surviving patients in both study groups
Measured: 28 days beginning from ICU admission (assessed at day 90)
90 day mortality rate
Number of non-surviving patients in both study groups
Measured: 90 days beginning from ICU admission (assessed at day 90)
Duration of renal replacement therapy
Use of organ support therapy (number of days on renal replacement therapy)
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2019
- Study start14 Nov 2019
- Primary completion7 Nov 2024
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for EndocarditisStudies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jörg Schefold, Insel Gruppe AG, University Hospital Bern
- Investigators
- Lars Englberger, MD, Study director, Inselspital, Bern University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03892174
- Sponsor's protocol ID
- RECREATE
- Acronym
- RECREATE
- Status last verified
- Nov 2024
- First submitted
- 22 Mar 2019
- Last updated
- 12 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 32282706
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03892174
- Acronym / sponsor ID
- RECREATE / RECREATE
- Conditions
- Endocarditis, Sepsis, Septic Shock
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Study start
- 14 Nov 2019 (actual)
- Primary completion
- 7 Nov 2024 (actual)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 27 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment protocol without adsorption | No intervention | – |
| Treatment protocol with adsorption | Active comparator | Other: Treatment protocol with adsorption |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (4 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Treatment protocol with adsorptionAdsorption while patients are in the OR on the extracorporeal circuit | Other | Treatment protocol with adsorption |
Primary outcome
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)
14 secondary outcomes
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
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).
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 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)
Length of ICU and hospital stay (days after surgical intervention).
Time frame: Number of days on ICU and in hospital (assessed at day 90)
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
Total amount of infused volume/transfusions on ICU
Time frame: 90 days
Duration of vasoactive drug therapy
Time frame: 90 days
Duration of invasive mechanical ventilation
Time frame: 90 days
ICU mortality rate
Time frame: ICU stay (assessed at day 90)
Hospital mortality rate
Time frame: hospital stay (assessed at day 90)
28 day mortality rate
Time frame: 28 days beginning from ICU admission (assessed at day 90)
90 day mortality rate
Time frame: 90 days beginning from ICU admission (assessed at day 90)
Duration of renal replacement therapy
Time frame: 90 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2024.
- Derived from this study: PubMed 32282706Gisler 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Lars Englberger, MD study director
Inselspital, Bern University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Treatment protocol with adsorption in people with Endocarditis and Sepsis, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Joerg C Schefold, MD (0041-31-632 ext. 5397, joerg.schefold@insel.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03892174, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Nov 2024.