- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04571801
Optimization of Sepsis Therapy Based on Patient-specific Digital Precision Diagnostics (DigiSep)
Sepsis is triggered by an infection and represents one of the greatest challenges of modern intensive care medicine. With regard to a targeted antimicrobial treatment strategy, the earliest possible pathogen detection is of crucial importance. Until now, culture-based detection methods represent the diagnostic gold standard, although they are characterized by numerous limitations. Culture-independent molecular diagnostic procedures may represent a promising alternative. In particular, the concept of plasmatic detection of circulating, free DNA employing next-generation sequencing (NGS) has shown to be suitable for the detection of disease-causing pathogens in patients with bloodstream infections.
The DigiSep-Trial is a randomized, controlled, interventional, multicenter trial to characterize the effect of the combination of NGS-based digital precision diagnostics, standard-of-care microbiological analyses and optional expert exchanges compared to solely standard-of-care microbiological analyses in the clinical picture of sepsis / septic shock. The study examines in 410 patients (n = 205 per arm) with sepsis / septic shock whether the so-called DOOR-RADAR (Desirability of Outcome Ranking / Response Adjusted for Duration of Antibiotic Risk) score (representing a combined endpoint including the criteria (1) inpatient admission time, (2) consumption of antibiotics, (3) mortality and (4) acute renal failure (ARF)) can be significantly improved, by application of an additional NGS-based diagnostic concept. We also aim to investigate whether the new diagnostic procedure is cost-effective. It is postulated that the inpatient admission time, mortality rate, incidence of ARF, the duration of antimicrobial therapy as well as the costs of complications and outpatient aftercare can be reduced. Moreover, a significant improvement in the quality of life (QoL) of the affected patients can be expected.
Extensive preparatory work suggests that NGS-based diagnostics have higher specificity and sensitivity compared to standard-of-care microbiological analyses for detecting bloodstream infections. This preliminary work for the DigiSep-Trial with the help of an interventional study design provides the optimal basis to establish this new concept as part of the national standard based on the best possible evidence.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Sepsis is a disease which is triggered by an infection and represents one of the greatest challenges of modern intensive care medicine. With regard to targeted anti-microbial therapy, the earliest possible pathogen detection is of crucial importance. Until now, culture-based detection methods represent the gold standard for diagnosis, although numerous limitations characterize these. In this context, culture-independent molecular biological processes are an alternative. In particular, the concept of serum detection of circulating, free DNA employing next-generation sequencing (NGS) seems to represent a promising diagnostic procedure in patients with bloodstream infections. The applicant's extensive preparatory work suggests that NGS-based diagnostics using the SIQ score have higher specificity and sensitivity compared to traditional culture-based methods for detecting bloodstream infections. This preliminary work for the DigiSep trial with the help of interventional study design provides the optimal basis to establish this new concept as part of the national standard based on the best possible evidence. The DigiSep trial is intended to characterize the effect of the combination of digital precision diagnostics, expert exchange and culture-based standard diagnostics compared to a purely culture-based conventional diagnosis in the clinical picture of sepsis / septic shock. The study examines in 410 patients (n = 205 per arm) with sepsis / septic shock whether the so-called DOOR-RADAR score (Desirability of Outcome Ranking / Response Adjusted for Duration of Antibiotic Risk Score) can be significantly improved, by application of the NGS. We also aim to also study whether the new procedure is cost-effective. It is postulated that the inpatient admission time, mortality rate, incidence of acute renal failure (ARF), the duration of anti-microbial therapy as well as the costs of complications and outpatient aftercare can be reduced. Also, a significant improvement in the quality of life of the affected patients can be expected.
As part of the study, the essential data is collected once at the time of sepsis (= onset). The culture-based diagnostics include the guideline-oriented collection of 2 blood culture sets (2 x aerobic / 2 x anaerobic) to the onset and three days later. At the same time, serum samples are obtained for NGS-based pathogen diagnostics. Additional sampling for NGS-based diagnostics can be made up to day 14 after onset or whenever the attending physician establishes a clinical indication for the collection of further blood cultures. The aforementioned cultures vs NGS-based pathogen diagnostics are also accompanied by extended immunological monitoring from blood plasma samples as well as an NGS-based transcriptome analysis. The associated sampling takes place at the time of onset, 3, 7 and 14 days after the beginning of sepsis. Routine microbiological findings from other biological samples (e.g. surgical swabs, drainage secretions, tracheal secretions, tissue samples) are included in the evaluation if these were collected three days before or after the extraction of serum samples for NGS-based diagnostics. The clinical data collection is also carried out at the time of sepsis (= onset), 3, 7 and 14 days later, analogous to the above-mentioned sample collection. The final outcome evaluation takes place 28 days (= 28 d) after the onset of sepsis. The study-related burden on the individual study patient includes a total of 17 ml of whole blood for NGS-based diagnostics, the four samples of 7.5 ml of whole blood for immunological monitoring and the four samples of 2.7 ml of whole blood for transcriptome analysis. The minimum total volume, therefore, amounts to the collection of approximately 75 ml of whole blood within the first 14 days after the onset of sepsis. The sampling takes place with the collection of the blood cultures or within the framework of the daily routine blood samples so that no further venous punctures are required here. Infection parameters such as procalcitonin (PCT) are carried out within the framework of daily regular blood collection and therefore, do not require any additional vascular punctures. The same principle applies to the collection of blood cultures which are routinely obtained as part of standard diagnostics in patients with suspected or proven sepsis. The required blood samples of two 40 ml of whole blood (each two sets of 2 x aerobic / 2 x anaerobic = 4 x 10 ml = 40 ml) therefore do not represent any additional burden due to the study. A further additional burden for the patient concerning invasive procedures or examinations is not expected in the study.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Thorsten Brenner, MD
- Phone Number: 1401 +49 201 723
- Email: thorsten.brenner@uk-essen.de
Study Contact Backup
- Name: Marc M Berger, MD
- Phone Number: 1401 +49 201 723
- Email: marc.berger@uk-essen.de
Study Locations
-
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Berlin, Germany
- Not yet recruiting
- University Hospital Charité
-
Contact:
- Stefan Schaller, MD
- Phone Number: 531012 0049 30 450
- Email: stefan.schaller@charite.de
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Baden-Württemberg
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Heidelberg, Baden-Württemberg, Germany
- Not yet recruiting
- University Hospital Heidelberg
-
Contact:
- Markus Weigand, MD
- Phone Number: 6110 +49 622156
- Email: markus.weigand@med.uni-heidelberg.de
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Heidenheim, Baden-Württemberg, Germany
- Not yet recruiting
- Heidenheim Hospital
-
Contact:
- Alexander Brinkmann, MD
- Phone Number: 2212 0049 7321 33
- Email: alexander.brinkmann@kliniken-heidenheim.de
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Konstanz, Baden-Württemberg, Germany
- Not yet recruiting
- Konstanz Hospital
-
Contact:
- Wolfgang Krüger, MD
- Phone Number: 1001 0049 7531 801
- Email: anaesthesiologie.kn@glkn.de
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Tübingen, Baden-Württemberg, Germany
- Not yet recruiting
- University Hospital Tübingen
-
Contact:
- Peter Rosenberger, MD
- Phone Number: 86622 0049 7071 29
- Email: peter.rosenberger@med.uni-tuebingen.de
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Ulm, Baden-Württemberg, Germany
- Not yet recruiting
- University Hospital Ulm
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Contact:
- Hendrik Bracht, MD
- Phone Number: 60237 0049 731 500
- Email: Hendrik.Bracht@uniklinik-ulm.de
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Bayern
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München, Bayern, Germany
- Not yet recruiting
- University Hospital TU München
-
Contact:
- Kristina Fuest, MD
- Phone Number: 8462 0049 89 4140
- Email: kristina.fuest@tum.de
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Regensburg, Bayern, Germany
- Not yet recruiting
- University Hospital Regensburg
-
Contact:
- Diane Bitzinger, MD
- Phone Number: 7801 0049 941 944
- Email: diane.bitzinger@ukr.de
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Würzburg, Bayern, Germany
- Not yet recruiting
- University Hospital Würzburg
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Contact:
- Patrick Meybohm, MD
- Phone Number: 30001 +49 931 201
- Email: meybohm_p@ukw.de
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Brandenburg
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Luckau, Brandenburg, Germany
- Not yet recruiting
- Klinik Evangelisches Krankenhaus Luckau gGmbH
-
Contact:
- Ulrike Jäkel, MD
- Phone Number: 142 0049 3544 58
- Email: Ulrike.Jaekel@diakonissenhaus.de
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Hessen
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Frankfurt, Hessen, Germany
- Not yet recruiting
- University Hospital Frankfurt
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Contact:
- Simone Lindau
- Phone Number: 5868 +49 69 6301
- Email: simone.lindau@kgu.de
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Wiesbaden, Hessen, Germany
- Not yet recruiting
- Helios Dr. Horst Schmidt Hospital
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Contact:
- Tobias Bingold, MD
- Phone Number: 2176 0049 611 43
- Email: tobias.bingold@helios-gesundheit.de
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Mecklenburg-Vorpommern
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Rostock, Mecklenburg-Vorpommern, Germany
- Not yet recruiting
- University Hospital Rostock
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Contact:
- Tobias Schürholz, MD
- Phone Number: 6401 0049 381494
- Email: anaesthesiologie@med.uni-rostock.de
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Niedersachsen
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Göttingen, Niedersachsen, Germany
- Not yet recruiting
- University Hospital Göttingen
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Contact:
- Onnen Mörer, MD
- Phone Number: 7744 +49 551 396
- Email: omoerer@med.uni-goettingen.de
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Hannover, Niedersachsen, Germany
- Not yet recruiting
- University Hospital Hannover (MHH)
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Contact:
- Klaudiusz Suchodolski, MD
- Phone Number: 2489 +49 511 532
- Email: Suchodolski.Klaudiusz@mh-hannover.de
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Nordrhein-Westfalen
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Aachen, Nordrhein-Westfalen, Germany
- Not yet recruiting
- University Hospital Aachen
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Contact:
- Lukas Martin, MD
- Phone Number: 80444 0049 241 80
- Email: lmartin@ukaachen.de
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Bielefeld, Nordrhein-Westfalen, Germany
- Not yet recruiting
- Klinik Evangelisches Krankenhaus Bethel gGmbH Bielefeld
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Contact:
- Friedhelm Bach, MD
- Phone Number: 79102 +49 521 772
- Email: ains@evkb.de
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Bonn, Nordrhein-Westfalen, Germany
- Not yet recruiting
- University Hospital Bonn
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Contact:
- Christian Putensen, MD
- Phone Number: 14119 +49 228 287
- Email: intensivmedizin@ukbonn.de
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Düsseldorf, Nordrhein-Westfalen, Germany
- Not yet recruiting
- University Hospital Düsseldorf
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Contact:
- Timo Brandenburger, MD
- Phone Number: 08900 +49 (0)211 81
- Email: timo.brandenburger@med.uni-duesseldorf.de
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Essen, Nordrhein-Westfalen, Germany
- Recruiting
- University Hospital Essen
-
Contact:
- Thorsten Brenner, MD
- Phone Number: 1401 0049 201 723
- Email: thorsten.brenner@uk-essen.de
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Köln, Nordrhein-Westfalen, Germany
- Not yet recruiting
- University Hospital Köln
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Contact:
- Fabian Dusse, MD
- Phone Number: 82058 +49 221 478
- Email: fabian.dusse@uk-koeln.de
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Sachsen
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Leipzig, Sachsen, Germany
- Not yet recruiting
- University Hospital Leipzig
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Contact:
- Sirak Petros, MD
- Phone Number: 127000 0341 - 97
- Email: Sirak.Petros@uniklinik-leipzig.de
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- All patients who develop sepsis or septic shock within < 24 h in accordance with the new sepsis definition (Sepsis-3) in the above-mentioned participating centers and consent to participation in the study will be included.
General inclusion criteria:
- Written consent by the study participant or a legally appointed representative
- Age >18 years
Sepsis:
- Life-threatening organ dysfunction due to a dysregulated immune response on the basis of a suspected or proven infection
- Detection of organ dysfunction indicated by SOFA score of ≥ 2 points Alternative:
Change of the quick (q) SOFA score of 2 points as an indication of a sepsis
Or septic shock:
- Persistent hypotension despite adequate volume substitution, which necessitates the use of vasopressors, to maintain an arterial medium pressure of > 65 mmHg
- Serum lactate > 2 mmol/l (18 mg/dl)
Exclusion Criteria:
- Age < 18 years
- Refusal to participate in the study
- Probable discharge of the patient from the intensive care unit within the first 72 h of initial study inclusion
- Palliative therapy approach
- Death of the patient is already foreseeable or inevitable at trial inclusion
- Patients who have already been included in the study but require re-admission to the intensive care unit cannot be included a second
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: 1
Standard diagnostics
|
Standard diagnostics (Microbial diagnostics by means of standard culture methods + optional consultation of experts in the field of infectious diseases) within the first 72 h after diagnosis of sepsis / septic shock
|
Experimental: 2
Standard diagnostics + NGS
|
Standard diagnostics + NGS (Microbial diagnostics using standard culture methods + Next Generation Sequencing + optional consultation of experts in the field of infectious diseases) within the first 72 h after diagnosis of sepsis / septic shock
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Desirability of Outcome Ranking / Response Adjusted for Duration of Antibiotic Risk-Score
Time Frame: 28 days
|
DOOR/RADAR-score [points], (min. 1, max.
5), a lower score indicates a better outcome
|
28 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease severity
Time Frame: at 90 and 180 days
|
Long term mortality [%]
|
at 90 and 180 days
|
Disease severity
Time Frame: at 28, 90, and 180 days
|
Hospital length of stay [days]
|
at 28, 90, and 180 days
|
Degree of organ dysfunction/-failure
Time Frame: at 28, 90, and 180 days
|
Duration of mechanical ventilation [days]
|
at 28, 90, and 180 days
|
Degree of organ dysfunction/-failure
Time Frame: during 28 days
|
Length of time until shock resolution [hours]
|
during 28 days
|
Degree of organ dysfunction/-failure
Time Frame: at 28, 90, and 180 days
|
Ongoing need for renal replacement therapy [%]
|
at 28, 90, and 180 days
|
Microbiological outcome
Time Frame: at 28, 90, and 180 days
|
Cumulative need for anti-infective drugs [days]
|
at 28, 90, and 180 days
|
Microbiological outcome
Time Frame: during 28 days
|
Beginning of a targeted anti-infective treatment regimen [days]
|
during 28 days
|
Health economic outcome
Time Frame: at 28, 90, and 180 days
|
Utilization of healthcare ressources (outpatient and inpatient) [Euro]
|
at 28, 90, and 180 days
|
Health economic outcome
Time Frame: at 28, 90, and 180 days
|
Policyholder costs (outpatient and inpatient) [Euro]
|
at 28, 90, and 180 days
|
Economic outcome
Time Frame: at 28, 90, and 180 days
|
Disease-related absence from work [days]
|
at 28, 90, and 180 days
|
Quality-of-life (QoL) based on VR-36 questionnaire
Time Frame: 90 and 180 days
|
VR-36 questionnaire [points] including 2 summary components, 8 scales, 36 items, a higher score indicates a higher Quality-of-Life (QoL)
|
90 and 180 days
|
Quality-of-life (QoL) based on EQ-5D-5L questionnaire
Time Frame: at 0, 90 and 180 days
|
EQ-5D-5L questionnaire [points] including 10 items, a higher score indicates a higher Quality-of-Life (QoL)
|
at 0, 90 and 180 days
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Thorsten Brenner, MD, Department of Anesthesiology, University Hospital Essen
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- DigiSep 01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
- Informed Consent Form (ICF)
- Clinical Study Report (CSR)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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