Infective EndocarditisRemove-PilotNCT02727413
Inflammatory Mediator Profiles During Heart Valve Replacement Surgery
An observational study of Infective Endocarditis and Valvular Heart Disease, run by Jena University Hospital at 1 site in Germany.
Trial summary
The study aims at the comparative examination of pre-, intra- and post-operative release profiles of inflammatory and vasoactive mediators in patients undergoing heart valve surgery under cardiopulmonary bypass (CPB) due to either infectious endocarditis or degenerative valvular heart disease. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Infective Endocarditis, Valvular Heart Disease
- What is being tested?
- Blood sample collection and Assessment of signs of organ dysfunction
- Type of treatment
- Surgery or procedure
- How many people
- 40 participants
- Where
- 1 siteGermany
- Study dates
- Jun 2016to Feb 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
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
Study population: Patients diagnosed with infective endocarditis or valvular heart disease, undergoing cardiac surgery with cardiopulmonary bypass
Who may be able to join
- signed informed consent
- age > 18
- confirmed diagnosis of infective endocarditis or valvular heart disease
- scheduled surgical Intervention with CPB use
Who cannot join
- glucocorticoid dosage above Cushing threshold
- severe neutropenia (below 1000/mm3)
- immunosuppression or immunomodulatory therapy
- pregnancy
Trial locations and contacts
1 site in 1 country.
Germany1 site
Center for Clinical Studies, Jena University Hospital
Jena, Thuringia, 07747
About this study
Official title: Inflammatory and Vasoactive Mediator Profiles and Pathogen Characterization During Heart Valve Replacement Surgery
The study aims at the comparative examination of pre-, intra- and post-operative release profiles of inflammatory and vasoactive mediators in patients undergoing heart valve surgery under cardiopulmonary bypass (CPB) due to either infectious endocarditis or degenerative valvular heart disease. Specific attention will focus on the distinction between mediator release associated with infection and that resulting from CPB. Concomitantly identification and characterization of infectious pathogens in the circulation and in valvular samples will be carried out, together with the search for resistance-coding transcripts.
Read the detailed description
Exaggerated release of inflammatory mediators and endogenous vasoactive substances resulting from the coincident infection and surgical stress plays a role in post-operative organ failure and altered immune defense, thus contributing to unfavorable post-operative outcome.
Cardiopulmonary bypass (CPB) itself, even in the absence of IE, has been shown to modify cytokine and vasoactive mediator release and may cause organ failure. Tracing of release profiles of inflammatory cytokines and vasoactive mediators and their correlation with postoperative organ dysfunction in cardiac surgery for IE or non-IE patients aims at the assessment of the prognostic validity of these biomarkers and the evaluation of measures for their pro-active clearance during the surgical intervention.
Induction of inflammatory mediators and their temporal release profile may vary depending on the involved pathogens, which cannot be always identified by conventional techniques (blood culture). Since it is conceivable that identification of the involved pathogen could explain differences in cytokine secretory patterns in IE, use of advanced molecular technologies (NGS) will support the clarification of such relations. Analysis of transcripts encoding inflammatory and vasoactive mediators in blood cells will enable the surveillance of temporal oscillations in their profiles during the observation time frame. Transcriptome analysis of identified putative pathogens can also disclose features of antibiotic resistance.
- Conditions
- Infective Endocarditis, Valvular Heart Disease
- Being tested
- Blood sample collection, Assessment of signs of organ dysfunction
- Medical subject headings
- Endocarditis, Heart Valve Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood sample collectionProcedure or surgery
Drawing of 10 ml blood at inclusion, at the time of CPB connection, 60 min under CPB, at the time of CPB disconnection, 6, 24 and 48 hours post-surgery
Assessment of signs of organ dysfunctionOther
Also called SOFA score
Assessment of signs of organ dysfunction based on medical data prior to surgery, 24 and 48 hours post-surgery, and at the time of ICU discharge
| Study group | Role | What they receive |
|---|---|---|
| Infective endocarditis | Blood sample collection and assessment of signs of organ dysfunction in patients diagnosed with infective endocarditis in accordance with Duke criteria and scheduled for valve surgery Receives: Procedure: Blood sample collection; Other: Assessment of signs of organ dysfunction | |
| Valvular heart disease | Blood sample collection and assessment of signs of organ dysfunction in patients diagnosed with valvular heart disease, with no signs of infection, scheduled for valve replacement surgery Receives: Procedure: Blood sample collection; Other: Assessment of signs of organ dysfunction |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the plasma concentration versus time curve (AUC) of Procalcitonin
Plasma levels of Procalcitonin over time
Measured: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Area under the plasma concentration versus time curve (AUC) of C-reactive Protein (CRP)
Plasma Levels of CRP over time
Measured: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Area under the plasma concentration versus time curve (AUC) of Endothelin 1
Plasma Levels of Endothelin 1 over time
Measured: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Area under the plasma concentration versus time curve (AUC) of Tumor Necrosis Factor (TNF) alpha
Plasma Levels of TNF alpha over time
Measured: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 1beta
Plasma Levels of IL 1beta over time
Measured: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 6
Plasma Levels of IL 6 over time
Measured: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 10
Plasma Levels of IL 10 over time
Measured: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 18
Plasma Levels of IL 18 over time
Measured: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Secondary outcomes (7)
Area under the plasma concentration versus time curve (AUC) of pro-Adrenomedullin
Plasma Levels of pro-Adrenomedullin
Measured: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Area under the plasma concentration versus time curve (AUC) of pro-Arginine vasopressin
Plasma Levels of pro-Arginine vasopressin
Measured: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Area under the plasma concentration versus time curve (AUC) of pro-Atrial natriuretic peptide
Plasma Levels of pro-Atrial natriuretic peptide
Measured: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
SOFA Score
Changes in SOFA scores after surgery, as compared to pre-surgery baseline
Measured: 24 h before and 24 and 48 h after surgical intervention
Renal replacement therapy
Use and duration of renal replacement therapy
Measured: Over 7 days following surgery
Concomitant medication
Cumulative doses of applied vasopressors, corticosteroids and prostaglandins
Measured: During and 48 h upon completion of surgical intervention
In-hospital mortality
Post-surgical mortality over 30 days
Measured: 30 days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2016 (estimated)
- Study startJun 2016
- Primary completionFeb 2017
- Study completionFeb 2017
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 Infective EndocarditisStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jena University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Thermo Fisher Scientific, Inc
- Responsible party
- Sponsor
- Investigators
- Frank M Brunkhorst, MD, Study chair, Jena University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02727413
- Sponsor's protocol ID
- ZKS0071
- Acronym
- Remove-Pilot
- Status last verified
- Oct 2016
- First submitted
- 23 Mar 2016
- Last updated
- 24 Jun 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Diab M, Tasar R, Sponholz C, Lehmann T, Pletz MW, Bauer M, Brunkhorst FM, Doenst T. Changes in inflammatory and vasoactive mediator profiles during valvular surgery with or without infective endocarditis: A case control pilot study. PLoS One. 2020 Feb 3;15(2):e0228286. doi: 10.1371/journal.pone.0228286. eCollection 2020.
PubMed 32015566
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inflammatory and Vasoactive Mediator Profiles and Pathogen Characterization During Heart Valve Replacement Surgery
- ClinicalTrials.gov ID
- NCT02727413
- Acronym / sponsor ID
- Remove-Pilot / ZKS0071
- Conditions
- Infective Endocarditis, Valvular Heart Disease
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Jena University HospitalUniversity, hospital or other
- Collaborators
- Thermo Fisher Scientific, Inc
- Study start
- Jun 2016 (actual)
- Primary completion
- Feb 2017 (actual)
- Study completion
- Feb 2017 (actual)
- First posted
- 4 Apr 2016 (estimated)
- 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.
The study aims at the comparative examination of pre-, intra- and post-operative release profiles of inflammatory and vasoactive mediators in patients undergoing heart valve surgery under cardiopulmonary bypass (CPB) due to either infectious endocarditis or degenerative valvular heart disease. Specific attention will focus on the distinction between mediator release associated with infection and that resulting from CPB. Concomitantly identification and characterization of infectious pathogens in the circulation and in valvular samples will be carried out, together with the search for resistance-coding transcripts.
Detailed description
Exaggerated release of inflammatory mediators and endogenous vasoactive substances resulting from the coincident infection and surgical stress plays a role in post-operative organ failure and altered immune defense, thus contributing to unfavorable post-operative outcome.
Cardiopulmonary bypass (CPB) itself, even in the absence of IE, has been shown to modify cytokine and vasoactive mediator release and may cause organ failure. Tracing of release profiles of inflammatory cytokines and vasoactive mediators and their correlation with postoperative organ dysfunction in cardiac surgery for IE or non-IE patients aims at the assessment of the prognostic validity of these biomarkers and the evaluation of measures for their pro-active clearance during the surgical intervention.
Induction of inflammatory mediators and their temporal release profile may vary depending on the involved pathogens, which cannot be always identified by conventional techniques (blood culture). Since it is conceivable that identification of the involved pathogen could explain differences in cytokine secretory patterns in IE, use of advanced molecular technologies (NGS) will support the clarification of such relations. Analysis of transcripts encoding inflammatory and vasoactive mediators in blood cells will enable the surveillance of temporal oscillations in their profiles during the observation time frame. Transcriptome analysis of identified putative pathogens can also disclose features of antibiotic resistance.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Infective endocarditis | – | Procedure: Blood sample collection, Other: Assessment of signs of organ dysfunctionBlood sample collection and assessment of signs of organ dysfunction in patients diagnosed with infective endocarditis in accordance with Duke criteria and scheduled for valve surgery |
| Valvular heart disease | – | Procedure: Blood sample collection, Other: Assessment of signs of organ dysfunctionBlood sample collection and assessment of signs of organ dysfunction in patients diagnosed with valvular heart disease, with no signs of infection, scheduled for valve replacement surgery |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients diagnosed with infective endocarditis or valvular heart disease, undergoing cardiac surgery with cardiopulmonary bypass
Key inclusion criteria (4 listed)
- signed informed consent
- age > 18
- confirmed diagnosis of infective endocarditis or valvular heart disease
- scheduled surgical Intervention with CPB use
Key exclusion criteria (4 listed)
- glucocorticoid dosage above Cushing threshold
- severe neutropenia (below 1000/mm3)
- immunosuppression or immunomodulatory therapy
- pregnancy
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 |
|---|---|---|
| Blood sample collectionDrawing of 10 ml blood at inclusion, at the time of CPB connection, 60 min under CPB, at the time of CPB disconnection, 6, 24 and 48 hours post-surgery | Procedure or surgery | Infective endocarditis, Valvular heart disease |
| Assessment of signs of organ dysfunctionAlso: SOFA scoreAssessment of signs of organ dysfunction based on medical data prior to surgery, 24 and 48 hours post-surgery, and at the time of ICU discharge | Other | Infective endocarditis, Valvular heart disease |
Primary outcome
Area under the plasma concentration versus time curve (AUC) of Procalcitonin
Time frame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Plasma levels of Procalcitonin over time
Area under the plasma concentration versus time curve (AUC) of C-reactive Protein (CRP)
Time frame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Plasma Levels of CRP over time
Area under the plasma concentration versus time curve (AUC) of Endothelin 1
Time frame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Plasma Levels of Endothelin 1 over time
Area under the plasma concentration versus time curve (AUC) of Tumor Necrosis Factor (TNF) alpha
Time frame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Plasma Levels of TNF alpha over time
Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 1beta
Time frame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Plasma Levels of IL 1beta over time
Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 6
Time frame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Plasma Levels of IL 6 over time
Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 10
Time frame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Plasma Levels of IL 10 over time
Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 18
Time frame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Plasma Levels of IL 18 over time
7 secondary outcomes
Area under the plasma concentration versus time curve (AUC) of pro-Adrenomedullin
Time frame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Area under the plasma concentration versus time curve (AUC) of pro-Arginine vasopressin
Time frame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Area under the plasma concentration versus time curve (AUC) of pro-Atrial natriuretic peptide
Time frame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
SOFA Score
Time frame: 24 h before and 24 and 48 h after surgical intervention
Renal replacement therapy
Time frame: Over 7 days following surgery
Concomitant medication
Time frame: During and 48 h upon completion of surgical intervention
In-hospital mortality
Time frame: 30 days after surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2019.
- Derived from this study: PubMed 32015566Diab M, Tasar R, Sponholz C, Lehmann T, Pletz MW, Bauer M, Brunkhorst FM, Doenst T. Changes in inflammatory and vasoactive mediator profiles during valvular surgery with or without infective endocarditis: A case control pilot study. PLoS One. 2020 Feb 3;15(2):e0228286. doi: 10.1371/journal.pone.0228286. eCollection 2020.
- 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. This study is not recruiting at the moment.
Frank M Brunkhorst, MD study chair
Jena University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Infective Endocarditis and Valvular Heart Disease, run by Jena University Hospital at 1 site in Germany.
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 4 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: finished, as of the sponsor's last update on 24 Jun 2019. 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 Germany. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the plasma concentration versus time curve (AUC) of Procalcitonin (time frame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery). The study lists 8 primary outcomes in all. 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 NCT02727413, 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 24 Jun 2019.