Sepsis in the ICU-II

Sepsis in the Intensive Care Unit-II

Sepsis-induced cardiac dysfunction (SIMD) is a well-known phenomenon yet its diagnosis remains elusive with no accepted definition, or defining pathophysiological mechanism associated with this disease. Systolic dysfunction occurs in 20-70% of patients, and may be severe, yet does not appear to have any prognostic value for mortality. Diastolic function has also been variably described and seems to be related to short-term mortality. However, the contribution of left ventricular systolic and diastolic dysfunction to mortality in sepsis are still far from clear, with uncertain contribution from previous cardiovascular disease, vasopressor and inotropic drugs and mechanical ventilation. Another poorly investigated area is right ventricular dysfunction. Cor pulmonale occurs in up to 25% of patients with septic shock, and is invariably related to pulmonary haemodynamics and mechanical ventilation, yet very little is known about how this affects prognosis. Finally, although the outcome of disease is a function of multiple parameters, septic cardiomyopathy is most frequently characterized based on individual echocardiographic parameters, without considering their interactions or placing them in the context of biomarkers and clinically available haemodynamic data. Available relevant studies are often monocentric, and many fail to consider the various confounders that influence the clinical outcome in sepsis. Therefore, the diagnostic and prognostic value of combinations of clinical, biochemical and haemodynamic variables remains to be established.

Accordingly, the purpose of this study is to identify biomarkers and echocardiographic and haemodynamic signatures characteristic of specific outcomes in SIMD to support the diagnosis and prognosis in SIMD. Specific aims are:

1. To determine the association between left ventricular systolic and diastolic dysfunction, and adverse outcome in SIMD;
2. To determine the association between right ventricular systolic and diastolic dysfunction, and adverse outcome in SIMD;
3. To determine the association between novel biomarkers and adverse outcome in SIMD;
4. To determine the combined value of biomarker, echocardiographic, and haemodynamic variables for predicting adverse outcomes in SIMD;
5. To explore if there are different phenotypes of SIMD using unsupervised machine learning algorithms, and whether they are associated with adverse outcomes.

50 patients will be enrolled in a feasibility study to evaluate the logistical setup for acute echocardiography and biobanking facilities. A further 300 patients will be enrolled with inclusion from peripheral centers once feasibility is confirmed.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Septic Shock; Cardiomyopathies; Organ Failure, Multiple
• Intervention / Treatment: Other: Exposure is septic shock (defined according to Sepsis-III) and standard treatment according to departmental protocols.

Detailed Description

UPDATE 26 Feb 2022:

A pilot project was completedafter recruitment of 50 patients confirming the feasibility of data collection, study logistics, biomarker assay set-up and frequency of outcomes. Cancellation of non-COVID related research in 2020&2021 has caused significant delays. Recruitment of patients will continue during 2022&2023. At the time of writing 70 patients have been recruited across 4 centres.

• Study Type: Observational
• Enrollment (Anticipated): 330

Contacts and Locations

• Study Contact: Name: Michelle S Chew, MBBS, PHD; Phone Number: +46101030000; Email: michelle.chew@liu.se
• Study Contact Backup: Name: Henrik Andersson, MSc, PhD; Phone Number: +46101030000; Email: henrik.a.andersson@regionostergotland.se

Study Locations

• France
  • Dijon, France, 21000
    • Recruiting
    • Chu Dijon-Bourgogne
    • Contact: Belaid Bouhemad
    • Principal Investigator: Belaid Bouhemad, MD, PhD
  • Paris, France, 75015
    • Recruiting
    • CHU Georges Pompidou
    • Contact: Bernard Cholley, MD, PhD
    • Principal Investigator: Bernard Cholley, MD, PhD
• Sweden
  • Jönköping, Sweden, 55305
    • Not yet recruiting
    • Ryhov Sjukhus Jönköping
    • Contact: Fredrik Hammarskjöld, MD, PhD
    • Principal Investigator: Fredrik Hammarskjöld
  • Linköping, Sweden, 58185
    • Recruiting
    • Dept of Anaesthesia and Intensive Care
    • Contact: Henrik Andersson, PhD
    • Contact: Helen Didriksson, RN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All consecutive patients admitted to participating ICUs with a presumptive diagnosis of septic shock will be screened for eligibility. Patients fulfilling the Sepsis-III criteria for septic shock will included. Study inclusion must occur within 12h of ICU admission.

Description

Inclusion Criteria:

• Adult patients admitted to ICU and fulfilling the Sepsis-III criteria for septic shock

Exclusion Criteria:

• No informed consent
• Acute coronary syndromes

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Adult patients with septic shock; All adult (>=18 yo) patients admitted to participating ICUs with septic shock defined according to the Sepsis III criteria. Purely observation study with no intervention. Patients are exposed to septic shock and treatment according to standard departmental protocols at each centre.	Other: Exposure is septic shock (defined according to Sepsis-III) and standard treatment according to departmental protocols.; Collection of data, biomarker and echocardiography analysis will be centralized and blinded. Assessment of endpoints will be blinded.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myocardial injury	increased hsTnT	any time during ICU stay within the study period, up to 10 days
Organ failure free days	Organ failure	30 days of study inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30 day mortality	Short term mortality	30 days after study inclusion
365 day mortality	Long term mortality	365 days after study inclusion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory outcomes	Vasopressor inotropic score	during ICU stay, up to 10 days
Exploratory outcomes	Days free of mechanical ventilation	30 days of study inclusion

Collaborators and Investigators

• Sponsor: Linkoeping University
• Collaborators: CHU Dijon Bourgogne; Hospitaux Universitaires Paris Sud; Hôpital Dupuytren; CHU George Pompidou, Paris; Ryhov Hospital, Jönköping
• Investigators: Study Chair: Michelle Chew, MBBS, PhD, Linkoeping University Hospital; Principal Investigator: Bernard Cholley, MD, PhD, CHU George Pompidou; Principal Investigator: Belaid Bouhemad, MD, PhD, CHU Dijon; Principal Investigator: Fredrik Hammarsköjld, MD, PhD, Ryhov Hospital, Jönköping

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 17, 2018
• Primary Completion (ANTICIPATED): December 31, 2023
• Study Completion (ANTICIPATED): December 31, 2023

Study Registration Dates

• First Submitted: December 21, 2020
• First Submitted That Met QC Criteria: January 4, 2021
• First Posted (ACTUAL): January 5, 2021

Study Record Updates

• Last Update Posted (ACTUAL): March 14, 2022
• Last Update Submitted That Met QC Criteria: February 26, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Sepsis; Toxemia; Cardiomyopathies; Multiple Organ Failure
• Other Study ID Numbers: SICU-II

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No