Clinical trial NCT02727413: Inflammatory Mediator Profiles During Heart Valve Replacement Surgery
Official title: Inflammatory and Vasoactive Mediator Profiles and Pathogen Characterization During Heart Valve Replacement Surgery
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Infective Endocarditis
Valvular Heart Disease
Lead sponsor: Jena University Hospital
Sponsor class: OTHER
Collaborators: name: Thermo Fisher Scientific, Inc
First posted: 2016-04-04
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed with infective endocarditis or valvular heart disease, undergoing cardiac surgery with cardiopulmonary bypass

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* signed informed consent
* age \> 18
* confirmed diagnosis of infective endocarditis or valvular heart disease
* scheduled surgical Intervention with CPB use

Exclusion Criteria:

* glucocorticoid dosage above Cushing threshold
* severe neutropenia (below 1000/mm3)
* immunosuppression or immunomodulatory therapy
* pregnancy

Primary outcomes:
measure: Area under the plasma concentration versus time curve (AUC) of Procalcitonin
timeFrame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
measure: Area under the plasma concentration versus time curve (AUC) of C-reactive Protein (CRP)
timeFrame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
measure: Area under the plasma concentration versus time curve (AUC) of Endothelin 1
timeFrame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
measure: Area under the plasma concentration versus time curve (AUC) of Tumor Necrosis Factor (TNF) alpha
timeFrame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
measure: Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 1beta
timeFrame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
measure: Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 6
timeFrame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
measure: Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 10
timeFrame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
measure: Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 18
timeFrame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Secondary outcomes:
measure: Area under the plasma concentration versus time curve (AUC) of pro-Adrenomedullin
timeFrame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
measure: Area under the plasma concentration versus time curve (AUC) of pro-Arginine vasopressin
timeFrame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
measure: Area under the plasma concentration versus time curve (AUC) of pro-Atrial natriuretic peptide
timeFrame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
measure: SOFA Score
timeFrame: 24 h before and 24 and 48 h after surgical intervention
measure: Renal replacement therapy
timeFrame: Over 7 days following surgery
measure: Concomitant medication
timeFrame: During and 48 h upon completion of surgical intervention
measure: In-hospital mortality
timeFrame: 30 days after surgery
Other outcomes:
measure: Pathogen genotyping
timeFrame: Before and during intervention at the heart valve
measure: Resistance transcripts
timeFrame: During intervention at the heart valve
Locations:
city: Jena
country: Germany
facility: Center for Clinical Studies, Jena University Hospital
state: Thuringia
Study officials:
affiliation: Jena University Hospital
name: Frank M Brunkhorst, MD
role: STUDY_CHAIR
References:
citation: 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.