Study of Treatment's Echocardiographic Mechanisms

Study Overview
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Brief Summary
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This ancillary study determines whether the Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) [ClinicalTrials.gov Identifier: NCT03434028] treatment arms (restrictive fluids strategy vs. liberal fluid strategy) for early sepsis-induced hypotension are associated with differences in cardiac structure and function based on an echocardiogram at 24 hours after randomization. Secondarily, this ancillary study explores possible heterogeneity of treatment effect based on an echocardiogram performed shortly after randomization in CLOVERS.

Detailed Description
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The Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis: Study of Treatment's Echocardiographic Mechanisms (CLOVERS-STEM) study is an ancillary study to CLOVERS, a parent multi-center, prospective, phase 3 randomized non-blinded interventional trial of fluid treatment strategies in the first 24 hours for patients with sepsis-induced hypotension. The CLOVERS trial attempts to determine the impact of a restrictive fluids strategy (vasopressors first followed by rescue fluids) as compared to a liberal fluid strategy (fluids first followed by rescue vasopressors) on 90-day in-hospital mortality in patients with sepsis-induced hypotension. This ancillary study obtains echocardiograms among CLOVERS-enrolled patients who consent to CLOVERS-STEM at baseline and 24 hours later (secondarily, this study also measures serum troponin levels at baseline and 24 hours) to pursue three aims: 1. Evaluate for differences in left ventricular global longitudinal strain at 24 hours after randomization between treatment arms; 2. Evaluate for differences in right ventricular end diastolic area to left ventricular end diastolic area ratio at 24 hours after randomization between treatment arms; 3. Explore possible heterogeneity of treatment effect based on baseline echocardiogram.

Official Title
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Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis: Study of Treatment's Echocardiographic Mechanisms (CLOVERS-STEM)

Conditions
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Sepsis

Intervention / Treatment
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* Procedure: ECHO
* Procedure: Blood Draw


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Enrolled in the Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) Trial Exclusion Criteria: Lack of Informed Consent for this Ancillary Study Allergy to Ultrasound-Enhancing Agents

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Intervention<br>Participants will receive 2 ECHO's and 2 Blood Draws | Procedure: ECHO<br>* Echocardiogram at baseline and 24 hours later<br>Procedure: Blood Draw<br>* Blood Draw for Troponin Levels - 5ml at baseline and 24 hours later<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left Ventricular Contractility at 24 hours | Left Ventricular Global Longitudinal Strain | 24 +/- 6 Hours | 
| Right Ventricular Structure at 24 hours | Right Ventricular End Diastolic Area to Left Ventricular End Diastolic Area Ratio | 24 +/- 6 hours | 
| Day 3 delta SOFA | Difference between baseline and day 3 Sequential Organ Failure Assessment (SOFA) scores | at 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Right Ventricular Contractility at 24 hours | Right Ventricular Longitudinal Strain | 24 +/- 6 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fluid Management, Sepsis-Induced Hypotension, Vasopressors, Cardiac Contractility