Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04257292
Other study ID # 01
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date September 1, 2019
Est. completion date July 31, 2020

Study information

Verified date February 2020
Source Jena University Hospital
Contact Mahmoud A Diab, Dr. med.
Phone 03641
Email mahmoud.diab@med.uni-jena.de
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

Infective endocarditis is a deadly disease with a mortality rate between 20 and 40%. Antibiotic therapy is of utmost importance. It is primarily guided by microbial results from positive blood culture. However, culture-based microbiological diagnostic can identify the species, but not the strain or the genotypic characteristics of a pathogen. Identifying the strain can be of utmost clinical significance. S. aureus is the most common causative organism of IE worldwide (16%-32%). This pathogen causes massive valve destruction and abscesses, which is strongly dependent on the expression of virulence factors that vary between different S. aureus strains.

Functional characterization of S. aureus and determination of virulence factors can currently be achieved through cell culture-based assays (CCBA). However, these tests are very time consuming and cannot be performed as routine clinical diagnostics. Next Generation Sequencing (NSG) has the potential to identify the genotypic characteristics of the pathogen, which is important to determine its virulent potential.

The aim of this study is to evaluate the possible utilization of NGS in the prediction of virulence factors of S. aureus and to compare it to the virulence factors determined using CCBA.

Hopefully, by comparing the NGS and CCBA, the investigators will get a faster way of determining the possible virulence factors. The NGS method can be further utilized to describe the prevalence of different strains of bacteria in infected valve tissue and blood culture samples. The collected data will serve as a basis for further evaluation of the potentials of NGS-based Diagnosis of IE, as well as a comparison between NGS-guided antibiotic treatment and the standard of care antibiotic treatment.


Description:

The ability of the Staphylococcus aureus to produce massive valve destruction as well as abscesses and to switch from acute to chronic infection and vice versa is a significant issue in the modern treatment of infective endocarditis. Furthermore, the ability to produce different virulence factors to evade the immune defense mechanisms proves the treatment more difficult. Another conundrum is the proof of different S. aureus strains isolated from Blood culture samples and infected valve samples. This makes a possible treatment of S. aureus-based endocarditis more difficult than expected.

Isolation of Bacteria in the Blood culture samples can take much time (3-14 days), and Cell Culture-based assays (CCBA) are not regularly implemented as a diagnostic procedure. CCBA is not regularly used in the clinical setting due to the time consumption and high cost. The significance of the CCBA method lies in the determination of the possible virulence factors. Utilizing the Next Generation Sequence (NGS) method, it might be possible to gain this information about the culprit microorganism faster and to identify the different strains and virulence factors.

To date, such correlations between genetic information about virulence factors gained by NGS and phenotypic information obtained by cell culture-based assays have not yet been performed.If proven, the NGE based analysis of the pathogens and their phenotypical behavior could guide antimicrobial therapy and make it individualized. Blood culture and infected tissue valve samples will be examined using the NGS and CCBA. The investigators aim to compare the differences in virulence factor results in these two methods, to characterize the prevalence of different strains of S. aureus in the blood culture and valve samples and to evaluate the possible potentials of NGS-based diagnosis of IE and to compare the effects of the NGS-guided antimicrobial therapy to the standard of care therapy.


Recruitment information / eligibility

Status Recruiting
Enrollment 10
Est. completion date July 31, 2020
Est. primary completion date February 28, 2020
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria:

- patients with the diagnosis infective endocarditis and indication for heart surgery on a heart valve

- signed informed consent

- age =18 years

- pathogens (S. aureus) can be isolated from blood culture AND from the removed valve tissue

Exclusion Criteria:

- S. aureus can not be isolated from removed valve tissue

Study Design


Locations

Country Name City State
Germany Jena University Hospital, Clinic for Cardiothoracic surgery Jena

Sponsors (2)

Lead Sponsor Collaborator
Jena University Hospital Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany

Country where clinical trial is conducted

Germany, 

Outcome

Type Measure Description Time frame Safety issue
Primary biofilm growth ability of S. aureus strains isolated from the blood and heart tissue of included patients to build a biofilm through study completion (about 1 year)
Secondary invasion characteristics characteristics of the S. aureus strains isolated from the blood and heart tissue of included patients to invade other cells (host cell invasion; persistence in host cells; tests will be conducted in cell culture) through study completion (about 1 year)
Secondary adhesion characteristics characteristics of the S. aureus strains isolated from the blood and heart tissue of included patients to adhere to other human cells (important information regarding the ability to attach to heart tissue; test will be conducted in cell culture) through study completion (about 1 year)
Secondary toxine production characteristics of the S. aureus strains isolated from the blood and heart tissue of included patients regarding production of toxins which will lead to information about induction of inflammation processes and induction of host cell death through study completion (about 1 year)
See also
  Status Clinical Trial Phase
Recruiting NCT05862025 - Evaluation of the Usefulness of Echocardiography in Patients With Staphylococcus Aureus Bacteremia (ET-AUREUS Study). N/A
Completed NCT03590106 - Cardiac Surgery Peer Recovery Support Program N/A
Not yet recruiting NCT05563662 - SURgical Registry of ENDocarditis EuRope
Completed NCT00947817 - Impact of Endothelial Cell Activation and Modifications of Haemostasis Induced by Infective Endocarditis on the Risk of Embolism N/A
Recruiting NCT00624091 - Rationale, Design and Methods for the Early Surgery in Infective Endocarditis Study (ENDOVAL) Phase 4
Terminated NCT00695903 - Phase 2 Study of Safety, Efficacy, and Pharmacokinetics of Higher Doses of Daptomycin and Vancomycin in MRSA Bacteremia Phase 2
Recruiting NCT04992923 - Prospective Cohort Study of Patients With Infective Endocarditis at Pitié-Salpêtrière Hospital
Recruiting NCT03642379 - Cardiac Surgery Peer Support Recovery N/A
Recruiting NCT05264181 - Transcatheter Pulmonary Valve Implantation With SAPIEN 3 Valve
Active, not recruiting NCT03683355 - Characterization of RadiOlabeled Tracer Uptake Pattern in Noninfected Transcatheter Aortic Valves.
Not yet recruiting NCT00550823 - Cardiac Computarized Tomography in Infective Endocarditis N/A
Not yet recruiting NCT00562653 - Autoantibodies and Clinical Symptoms in Infective Endocarditis Patients N/A
Completed NCT03153384 - Impact of the Blood Culture Technique on the Diagnosis of Infective Endocarditis
Not yet recruiting NCT06194409 - The Incidence, Clinical Characteristics and Outcome of Infective Endocarditis Among Intravenous Drug Abusers Versus Non-Drug Abusers.
Completed NCT03945708 - Does Whole Blood Adsorber During CPB Reduce Vasoactive Drugs Postoperatively in Endocarditis Patients Undergoing Valve Surgery? N/A
Not yet recruiting NCT06269679 - CBCT vs OPT on the Oral Health Status at 12 Months of Patients Hospitalized for Infective Endocarditis. N/A
Recruiting NCT03626571 - PET/MR Imaging In Patients With Infective Endocarditis
Completed NCT03612245 - Hygiene and Bucco-dental Status of Patients With Oral Streptococcal Endocarditis
Completed NCT02910856 - Infective Endocarditis in the Elderly
Recruiting NCT02196753 - PET CT in Suspected CIED Infection, a Pilot Study - PET Guidance I N/A