Molecular Biomarkers for Sepsis

NCT04280354 | Terminated

• 1 other identifier: 2020-00297;qu18Egli3
• Study Type: observational
• Target: 3
• Locations: 1 country
• Sites: 15

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.

Conditions

Sepsis; Severe Community-acquired Pneumonia (sCAP); Infection, Bacterial

Keywords

Community-acquired Pneumonia; biomarker; clinical data warehouse (CDWH); machine learning; data-driven algorithms; multi-dimensional modelling; sepsis-related mortality; Streptococcus pneumoniae

Outcome Measures

Primary Outcomes (3)

• Detection of sepsis

  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).

  within 7 days after study inclusion

• Sepsis related mortality

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

  within 7 days after study inclusion

• Time to sepsis detection (minutes after Intensive Care Unit (ICU) admission)

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

  within 7 days after study inclusion

Study Arms (2)

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; Other: compare data patterns by data-driven algorithms 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; Other: compare data patterns by data-driven algorithms to predict sepsis-related mortality

Interventions

compare data patterns by data-driven algorithms to determine sepsis OTHER

compare data patterns by data-driven algorithms including machine learning and multi-dimensional modelling to reliably determine sepsis

patients with severe community acquired pneumonia (cases); patients without pneumonia or sepsis (controls)

compare data patterns by data-driven algorithms to predict sepsis-related mortality OTHER

compare data patterns by data-driven algorithms including machine learning and multi-dimensional modelling to to predict sepsis-related mortality

patients with severe community acquired pneumonia (cases); patients without pneumonia or sepsis (controls)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Adult patients fulfilling the WHO-definition of a severe community acquired pneumonia (sCAP, cases) and patients with an inflammatory phenotype (controls) requiring intensive care medicine.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (15)

Clinical Bacteriology and Mycology, University Hospital Basel

Basel, 4031, Switzerland

Location

Infectious Diseases and Hospital Epidemiology, University Hospital Basel

Basel, 4031, Switzerland

Location

Intensive Care Unit; University Hospital Basel

Basel, 4031, Switzerland

Location

Institute for Infectious Diseases, University of Bern

Bern, 3001, Switzerland

Location

Infectious Diseases and Hospital Epidemiology, University Hospital Bern

Bern, 3010, Switzerland

Location

Intensive Care Unit, University Hospital Bern

Bern, 3010, Switzerland

Location

Clinical Bacteriology, University Hospital Geneva

Geneva, 1205, Switzerland

Location

Infectious Diseases and Hospital Epidemiology, University Hospital Geneva

Geneva, 1205, Switzerland

Location

Intensive Care Unit, University Hospital Geneva

Geneva, 1205, Switzerland

Location

Clinical Microbiology, University Hospital Lausanne

Lausanne, 1011, Switzerland

Location

Infectious Diseases and Hospital Epidemiology , University Hospital Lausanne

Lausanne, 1011, Switzerland

Location

Intensive Care Unit, University Hospital Lausanne

Lausanne, 1011, Switzerland

Location

Infectious Diseases and Hospital Epidemiology, University Hospital Zurich

Zurich, 8091, Switzerland

Location

Institute for Medical Microbiology, University Hospital Zurich

Zurich, 8091, Switzerland

Location

Intensive Care Unit, University Hospital Zurich

Zurich, 8091, Switzerland

Location

Biospecimen

Retention: SAMPLES WITH DNA

All samples will be stored in a biobank on sepsis. In particular serum and DNA samples of hosts will be stored for at least 10 years to answer subsequent research questions.

MeSH Terms

Conditions

Sepsis; Community-Acquired Pneumonia; Bacterial Infections

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Community-Acquired Infections; Pneumonia; Respiratory Tract Infections; Respiratory Tract Diseases; Bacterial Infections and Mycoses

Study Officials

• Adrian Egli, PD Dr.

  Clinical Microbiology, University Hospital Basel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2020
• First Posted: February 21, 2020
• Study Start: February 16, 2022
• Primary Completion: July 31, 2022
• Study Completion: July 31, 2022
• Last Updated: May 9, 2024

Record last verified: 2024-05

Locations

CH (15)