Inflammatory Mediator Profiles During Heart Valve Replacement Surgery

Valvular Heart Disease Clinical Trial

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Official title:

Inflammatory and Vasoactive Mediator Profiles and Pathogen Characterization During Heart Valve Replacement Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02727413
• Other study ID #: ZKS0071
• Status: Completed
• Start date: June 2016
• Est. completion date: February 2017

Study information

• Verified date: October 2016
• Source: Jena University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: February 2017
• Est. primary completion date: February 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Endocarditis
• Endocarditis, Bacterial
• Heart Diseases
• Heart Valve Diseases
• Infective Endocarditis
• Valvular Heart Disease

Intervention

Procedure:
• Blood sample collection
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

Other:
• Assessment of signs of organ dysfunction
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

Locations

Country	Name	City	State
Germany	Center for Clinical Studies, Jena University Hospital	Jena	Thuringia

Sponsors (2)

Lead Sponsor	Collaborator
Jena University Hospital	Thermo Fisher Scientific

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pathogen genotyping	Identification of circulating pathogens	Before and during intervention at the heart valve
Other	Resistance transcripts	Abundance of bacterial transcripts encoding antibiotic resistance in blood	During intervention at the heart valve
Primary	Area under the plasma concentration versus time curve (AUC) of Procalcitonin	Plasma levels of Procalcitonin over time	24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Primary	Area under the plasma concentration versus time curve (AUC) of C-reactive Protein (CRP)	Plasma Levels of CRP over time	24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Primary	Area under the plasma concentration versus time curve (AUC) of Endothelin 1	Plasma Levels of Endothelin 1 over time	24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Primary	Area under the plasma concentration versus time curve (AUC) of Tumor Necrosis Factor (TNF) alpha	Plasma Levels of TNF alpha over time	24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Primary	Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 1beta	Plasma Levels of IL 1beta over time	24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Primary	Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 6	Plasma Levels of IL 6 over time	24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Primary	Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 10	Plasma Levels of IL 10 over time	24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Primary	Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 18	Plasma Levels of IL 18 over time	24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Secondary	Area under the plasma concentration versus time curve (AUC) of pro-Adrenomedullin	Plasma Levels of pro-Adrenomedullin	24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Secondary	Area under the plasma concentration versus time curve (AUC) of pro-Arginine vasopressin	Plasma Levels of pro-Arginine vasopressin	24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Secondary	Area under the plasma concentration versus time curve (AUC) of pro-Atrial natriuretic peptide	Plasma Levels of pro-Atrial natriuretic peptide	24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Secondary	SOFA Score	Changes in SOFA scores after surgery, as compared to pre-surgery baseline	24 h before and 24 and 48 h after surgical intervention
Secondary	Renal replacement therapy	Use and duration of renal replacement therapy	Over 7 days following surgery
Secondary	Concomitant medication	Cumulative doses of applied vasopressors, corticosteroids and prostaglandins	During and 48 h upon completion of surgical intervention
Secondary	In-hospital mortality	Post-surgical mortality over 30 days	30 days after surgery