Infective EndocarditisNESSIENCT04257292
NExt-Generation Sequencing and Cell Culture-based Characterization of S. Aureus in Infective Endocarditis
An observational study of Infective Endocarditis and Infection Staphylococcal, run by Jena University Hospital at 1 site in Germany.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Infective Endocarditis, Infection Staphylococcal
- How many people
- 10 participants
- Where
- 1 siteGermany
- Study dates
- 1 Sep 2019to 31 Jul 2020
- 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 with the diagnosis infective endocarditis and indication for heart surgery on a heart valve
Who may be able to join
- 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
Who cannot join
- S. aureus can not be isolated from removed valve tissue
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
Jena University Hospital, Clinic for Cardiothoracic surgery
Jena, 07747
Mahmoud A Diab, Dr. med., +49 3641 ext. 9322978, mahmoud.diab@med.uni-jena.de
Ilia Velichkov, +49 3641 ext. 9322947, ilia.velichkov@med.uni-jena.de
About this study
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.
Read more
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.
Read the detailed 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.
- Conditions
- Infective Endocarditis, Infection Staphylococcal
- Keywords
- Infective Endocarditis, Staphylococcus aureus, Next-Generation Sequencing
- Medical subject headings
- Endocarditis, Staphylococcal Infections
What is being measured
The primary outcome is the main question the study is designed to answer.
biofilm growth
ability of S. aureus strains isolated from the blood and heart tissue of included patients to build a biofilm
Measured: through study completion (about 1 year)
Secondary outcomes (3)
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)
Measured: through study completion (about 1 year)
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)
Measured: through study completion (about 1 year)
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
Measured: through study completion (about 1 year)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2020
- Study start1 Sep 2019
- Primary completion28 Feb 2020 (estimated)
- Study completion31 Jul 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 only
- Time perspective
- Prospective
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jena University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
- Responsible party
- Principal investigator, Mahmoud A. Diab, Jena University Hospital
- Investigators
- Mahmoud A Diab, Dr. med., Principal investigator, Jena University Hospital, Clinic for Cardiac and Thoracic Surgery
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04257292
- Sponsor's protocol ID
- 01
- Acronym
- NESSIE
- Status last verified
- Feb 2020
- First submitted
- 5 Sep 2019
- Last updated
- 6 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NExt-Generation Sequencing and Cell Culture-based Characterization of S. Aureus in Infective Endocarditis
- ClinicalTrials.gov ID
- NCT04257292
- Acronym / sponsor ID
- NESSIE / 01
- Conditions
- Infective Endocarditis, Infection Staphylococcal
- Keywords
- Infective Endocarditis, Staphylococcus aureus, Next-Generation Sequencing
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Jena University HospitalUniversity, hospital or other
- Collaborators
- Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
- Study start
- 1 Sep 2019 (actual)
- Primary completion
- 28 Feb 2020 (estimated)
- Study completion
- 31 Jul 2020 (estimated)
- First posted
- 6 Feb 2020 (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.
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.
Detailed 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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- patients with the diagnosis infective endocarditis and indication for heart surgery on a heart valve
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (1 listed)
- S. aureus can not be isolated from removed valve tissue
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
biofilm growth
Time frame: through study completion (about 1 year)
ability of S. aureus strains isolated from the blood and heart tissue of included patients to build a biofilm
3 secondary outcomes
invasion characteristics
Time frame: through study completion (about 1 year)
adhesion characteristics
Time frame: through study completion (about 1 year)
toxine production
Time frame: through study completion (about 1 year)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2020.
- Individual participant dataSharing planned: Undecided
Related trials for Infective Endocarditis
Not yet recruiting
Metabolic Profiling Among Patients Suspected of Infective Endocarditis - PPSIE Comparing Metabolomes of Bloodstream Infections Versus Infective Endocarditis
Infective Endocarditis (IE)
Recruiting
CBCT vs OPT on the Oral Health Status at 12 Months of Patients Hospitalized for Infective Endocarditis.
Infective Endocarditis
RecruitingObservational study
Impact of Preoperative Dental Screening in Reducing Infective Endocarditis Risk in Transcatheter Aortic Valve Implantation Patients
Transcatheter Aortic Valve Implantation, Dental
RecruitingPhase 3
Rifampin-free Regimen Versus Rifampin-containing Regimen in the Treatment of Staphylococcal Prosthetic Valve Endocarditis
Infective Endocarditis
Not yet recruitingObservational study
AngioVac Aspiration Therapy Registry
Intracardiac Thrombus, Intracardiac Mass
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.
Mahmoud A Diab, Dr. med. principal investigator
Jena University Hospital, Clinic for Cardiac and Thoracic Surgery
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 Infection Staphylococcal, 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 1 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: status not confirmed, as of the sponsor's last update on 6 Feb 2020. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mahmoud A Diab, Dr. med. (03641 ext. 9322978, mahmoud.diab@med.uni-jena.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
biofilm growth (time frame: through study completion (about 1 year)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Feb 2020.