Molecular Biomarkers for Sepsis

• Sponsor: University Hospital, Basel, Switzerland (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04280354
• Collaborator: Swiss Personalized Health Network (SPHN) (Other), Personalized Health and Related Technologies (PHRT) initiative of ETH Zürich (Other)
• Enrollment: 400
• Locations: 15
• Anticipated Duration (Months): 18
• Patients Per Site: 26.7
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

This multi-center observational case-control study in Intensive Care Unit (ICU) patients is to identify novel biomarkers allowing to recognize severe community acquired pneumonia (sCAP) -associated sepsis at an earlier stage and predict sepsis-related mortality. Patients with sCAP (cases) will be profoundly characterized over time regarding the development of sepsis and compared with control patients. The mechanisms and influencing factors on the clinical course will be explored with most modern -omics technologies allowing a detailed characterisation. These data will be analysed using machine learning algorithms and multi-dimensional mathematical models.

Condition or Disease	Intervention/Treatment	Phase
Sepsis; Severe Community-acquired Pneumonia (sCAP); Infection, Bacterial	Other: compare data patterns by data-driven algorithms to determine sepsis; Other: compare data patterns by data-driven algorithms to predict sepsis-related mortality

Study Design

• Study Type: Observational
• Anticipated Enrollment: 400 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Prospective Study to Discover New Biomarkers for Early Detection of Sepsis and Prediction of Sepsis-related Mortality in Patients With Severe Community Acquired Pneumonia (sCAP)
• Anticipated Study Start Date: Apr 1, 2022
• Anticipated Primary Completion Date: Oct 1, 2023
• Anticipated Study Completion Date: Oct 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
patients with severe community acquired pneumonia (cases) Cases: Patients with severe community acquired pneumonia with required ICU admission.	Other: compare data patterns by data-driven algorithms to determine sepsis; compare data patterns by data-driven algorithms including machine learning and multi-dimensional modelling to reliably determine sepsis; Other: compare data patterns by data-driven algorithms to predict sepsis-related mortality; compare data patterns by data-driven algorithms including machine learning and multi-dimensional modelling to to predict sepsis-related mortality
patients without pneumonia or sepsis (controls) Controls: Clinical phenotype of inflammation not due to suspected sepsis; patients with fever >38°C, C reactive Protein (CRP) >100mg/L, no infection focus expected in ≥ 24h.	Other: compare data patterns by data-driven algorithms to determine sepsis; compare data patterns by data-driven algorithms including machine learning and multi-dimensional modelling to reliably determine sepsis; Other: compare data patterns by data-driven algorithms to predict sepsis-related mortality; compare data patterns by data-driven algorithms including machine learning and multi-dimensional modelling to to predict sepsis-related mortality

Outcome Measures

Primary Outcome Measures

1. Detection of sepsis [within 7 days after study inclusion]

   Sepsis detection based on new discovered digital biomarkers will be compared to classical sepsis-3 criteria (with an increase of the sequential organ failure assessment (SOFA) score of 2 or larger score points).

2. Sepsis related mortality [within 7 days after study inclusion]

   Prediction of sepsis related mortality (with >80% sensitivity and specificity at least 24h prior to event)

3. Time to sepsis detection (minutes after Intensive Care Unit (ICU) admission) [within 7 days after study inclusion]

   Time to sepsis detection (minutes after ICU admission) based on machine learning

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Admission to the ICU of one of the participating centers.

• Cases: severe community acquired pneumonia with requirement for ICU admission.

• Controls: Clinical phenotype of inflammation not due to suspected sepsis In addition, control patients will be patients with fever >38°C, CRP >100mg/L, no infection focus expected in ≥ 24h.

• All required sample types can most likely be collected within the first 24h visits.

• Expected ICU stay of more than 24h.

Exclusion Criteria:

• Admission to the hospital within the prior 14 days.

• Patients with psychosis

• Evidence of a hospital acquired pneumonia.

• One of the following respiratory conditions: Acute exacerbation of chronic obstructive pulmonary disease (COPD) or bronchiectasis, acute severe asthma, aspiration pneumonia, tuberculosis, clinical suspected viral pneumonia without bacterial infection, cardiogenic pulmonary oedema.

• Patients with an acute respiratory distress Syndrome (ARDS).

• Patient which can be managed as outpatients and do not require an ICU.

• Patient where a transmission to another institution is likely within the next 24h.

• Documented rejection of the general consent or participation to research in general.

• Patients with a palliative situation and a life expectancy due to other diseases (e.g. progressed cancer) less than 28 days.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Bacteriology and Mycology, University Hospital Basel	Basel		Switzerland	4031
2	Infectious Diseases and Hospital Epidemiology, University Hospital Basel	Basel		Switzerland	4031
3	Intensive Care Unit; University Hospital Basel	Basel		Switzerland	4031
4	Institute for Infectious Diseases, University of Bern	Bern		Switzerland	3001
5	Infectious Diseases and Hospital Epidemiology, University Hospital Bern	Bern		Switzerland	3010
6	Intensive Care Unit, University Hospital Bern	Bern		Switzerland	3010
7	Infectious Diseases and Hospital Epidemiology, University Hospital Geneva	Geneva,		Switzerland	1205
8	Clinical Bacteriology, University Hospital Geneva	Geneva		Switzerland	1205
9	Intensive Care Unit, University Hospital Geneva	Geneva		Switzerland	1205
10	Clinical Microbiology, University Hospital Lausanne	Lausanne		Switzerland	1011
11	Infectious Diseases and Hospital Epidemiology , University Hospital Lausanne	Lausanne		Switzerland	1011
12	Intensive Care Unit, University Hospital Lausanne	Lausanne		Switzerland	1011
13	Infectious Diseases and Hospital Epidemiology, University Hospital Zurich	Zürich		Switzerland	8091
14	Institute for Medical Microbiology, University Hospital Zurich	Zürich		Switzerland	8091
15	Intensive Care Unit, University Hospital Zurich	Zürich		Switzerland	8091

Sponsors and Collaborators

• University Hospital, Basel, Switzerland
• Swiss Personalized Health Network (SPHN)
• Personalized Health and Related Technologies (PHRT) initiative of ETH Zürich

Investigators

• Principal Investigator: Adrian Egli, PD Dr., Clinical Microbiology, University Hospital Basel

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University Hospital, Basel, Switzerland
• ClinicalTrials.gov Identifier: NCT04280354
• Other Study ID Numbers: 2020-00297;qu18Egli3
• First Posted: Feb 21, 2020
• Last Update Posted: Apr 7, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University Hospital, Basel, Switzerland: Community-acquired Pneumonia; biomarker; clinical data warehouse (CDWH); machine learning; data-driven algorithms; multi-dimensional modelling; sepsis-related mortality; Streptococcus pneumoniae
• Additional relevant MeSH terms: Pneumonia; Sepsis; Toxemia; Bacterial Infections

Study Results

No Results Posted as of Apr 7, 2022