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Micro and Macro Circulation in Sepsis (DAISY)

Primary Purpose

Sepsis, Septic Shock

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Starling SV- Passive Leg Raise
Microscan Sublingual Microscopy
Vexus Ultrasound Scoring
Urine Collection
Sponsored by
Denver Health and Hospital Authority
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Sepsis

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Septic Patient Cohort: Greater than or equal to 18 years of age Diagnosed with sepsis or septic shock Require admission to the Hospital Control Cohort: Greater than or equal to 18 years of age Undergoing elective surgery requiring intubation and general anesthesia Exclusion Criteria: Patients with any of the following characteristics will be excluded Less than 18 years old Chronic Kidney disease on dialysis Currently pregnant Incarcerated persons Control Cohort: Less than 18 years old History of Chronic Kidney disease on dialysis, uncontrolled diabetes, cirrhosis, heart failure, or nephritic or nephrotic syndromes. Currently pregnant Incarcerated persons

Sites / Locations

  • Denver Health Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Septic Patient Interventions

Control Patient Interventions

Arm Description

Septic Patients will have all interventions performed: Urine collection, Passive Leg Raise, Ultrasound and sublingual microscopy

Control patients will have urine collection and sublingual microscopy performed when intubated

Outcomes

Primary Outcome Measures

Need for Renal Replacement Therapy
Renal Replacement Therapy will be monitored whil hospitalized for Sepsis/Septic Shock.

Secondary Outcome Measures

Inpatient Mortality
Patient Death while hospitalized for the admission of Sepsis/Septic Shock
90 day survival
Patient death within 90 days of admission to the hospital for Sepsis/Septic Shock

Full Information

First Posted
January 5, 2023
Last Updated
January 13, 2023
Sponsor
Denver Health and Hospital Authority
Collaborators
National Institutes of Health (NIH)
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1. Study Identification

Unique Protocol Identification Number
NCT05694455
Brief Title
Micro and Macro Circulation in Sepsis
Acronym
DAISY
Official Title
Clinical Utility of Longitudinal Measurement of Hemodynamic Incoherence and Endothelial
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2022 (Actual)
Primary Completion Date
June 30, 2023 (Anticipated)
Study Completion Date
June 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Denver Health and Hospital Authority
Collaborators
National Institutes of Health (NIH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
Purpose: To assess the prognostic role of Handheld Vital Microscopy (HVM) and evaluate levels of endothelial glycocalyx (eGC) breakdown in patients demonstrating Hemodynamic Incoherence (HI), to elucidate a mechanistic link between the eGC and HI in order to inform prognostic enrichment of future resuscitation trials. We will serially evaluate MiH and the perfused boundary region (PBR, an visual proxy for eGC thickness) using HVM, and a validated circulating biomarker of eGC integrity.
Detailed Description
There are few reliable prognostic indicators in early sepsis to predict disease progression, in part because the pathophysiologic mechanism of vascular dysregulation remains incompletely understood. The global COVID-19 pandemic has increased the number of patients with sepsis, straining hospital systems and illustrating the need for research into prognostic and therapeutic strategies.1 An important area of research is the role of the eGC, a thin vascular lining composed of proteoglycans, glycosaminoglycan side-chains, and plasma proteins that play a central role in microvascular homeostasis, the function of which is compromised in sepsis.2, 3 Another growing field of inquiry is the phenomenon of HI, a condition in which MiH remain dysfunctional despite normalization of conventionally targeted MaH measures such as mean arterial pressure (MAP), leading to poor end-organ perfusion.4, 5 It has been hypothesized that HI due to persistently deranged MiH and reduced end-organ perfusion result in an ongoing state of "microvascular shock", leading to worsening end-organ damage despite apparent normalization of conventionally targeted parameters.5 Importantly, HI has been shown to predict poor patient outcomes, with abnormal MiH predicting patient mortality despite normalization of MAP after administration of vasoactive medications.4, 6 MiH measures have also been shown to differ significantly between septic patients and healthy controls.2 In one study of a large sepsis cohort, MiH parameters were predictive of adverse outcomes, while MaH parameters were not, suggesting that MiH measurements, and HI in particular may be more sensitive than conventional measures for predicting outcomes in sepsis.7 One hypothesis is that HI in sepsis is mediated by degradation of the eGC, with subsequent loss of microvascular homeostasis, though the role of the eGC as a vascular barrier remains controversial.8 One question that remains is whether or not microvascular changes can predict patient outcomes in patients judged to be adequately fluid resuscitated, as measured by MAP or NICOM testing.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sepsis, Septic Shock

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Patients diagnosed with septic shock in the emergency department admitted to the hospital will be enrolled within 4 hours of the emergency physician's decision to admit the patient to the hospital. On enrollment, On enrollment and at hours 10-14, 22-26, and 44-48, the research team will assess MiH and MaH as well as the total amount of IV fluids and vasoactive medications administered, demographics, charlston morbidity scale and Sofa score. Healthy controls will have sublingual microscopy and urine collection performed at time of intubation for elextive procedure
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Septic Patient Interventions
Arm Type
Other
Arm Description
Septic Patients will have all interventions performed: Urine collection, Passive Leg Raise, Ultrasound and sublingual microscopy
Arm Title
Control Patient Interventions
Arm Type
Other
Arm Description
Control patients will have urine collection and sublingual microscopy performed when intubated
Intervention Type
Diagnostic Test
Intervention Name(s)
Starling SV- Passive Leg Raise
Other Intervention Name(s)
Baxter Starling SV
Intervention Description
All septic patients will have a passive leg raise performed with the assistance of an starling SV device to look at SV change. This will be performed at admission and 4 hours after admission. This intervention will not be performed on healthy controls
Intervention Type
Diagnostic Test
Intervention Name(s)
Microscan Sublingual Microscopy
Other Intervention Name(s)
Microvision Sublingual Microscopy
Intervention Description
All septic patients will have sublingual microscopic images performed at admission, 8-16 hours, 48 hours and 72 hours. Control patients will have a sublingual microscope imaging perfomed after intubation for the elective procedure. This is a process of a 2cm probe tip gently placed on patients' mouth and 3 different images of 5-8 seconds are recorded.
Intervention Type
Diagnostic Test
Intervention Name(s)
Vexus Ultrasound Scoring
Intervention Description
All septic Patients will have this performed on all patients at admission, 8-16 hours, 48 hours and 72 hours. Ultrasound images and blood flow waves will be collected of the IVC diameter, hepatic vein, portal vein, renal veins and scored using the Venous Excess Ultrasound (VExUS scale). Healthy controls will not have ultrasound performed
Intervention Type
Other
Intervention Name(s)
Urine Collection
Intervention Description
The urine assay is collected passively from the patient will be ran through a DMMB assay- could provide future beneficial information to resuscitation efforts. This will be performed on all septic patients at admission, 8-16 hours, 48 hours and 72 hours. Urine will be collected on healthy controls at time of intubation for elective procedure.
Primary Outcome Measure Information:
Title
Need for Renal Replacement Therapy
Description
Renal Replacement Therapy will be monitored whil hospitalized for Sepsis/Septic Shock.
Time Frame
90 day
Secondary Outcome Measure Information:
Title
Inpatient Mortality
Description
Patient Death while hospitalized for the admission of Sepsis/Septic Shock
Time Frame
90 day
Title
90 day survival
Description
Patient death within 90 days of admission to the hospital for Sepsis/Septic Shock
Time Frame
90 day

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Septic Patient Cohort: Greater than or equal to 18 years of age Diagnosed with sepsis or septic shock Require admission to the Hospital Control Cohort: Greater than or equal to 18 years of age Undergoing elective surgery requiring intubation and general anesthesia Exclusion Criteria: Patients with any of the following characteristics will be excluded Less than 18 years old Chronic Kidney disease on dialysis Currently pregnant Incarcerated persons Control Cohort: Less than 18 years old History of Chronic Kidney disease on dialysis, uncontrolled diabetes, cirrhosis, heart failure, or nephritic or nephrotic syndromes. Currently pregnant Incarcerated persons
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
August Longino, MD
Phone
801-9033258
Email
August.longino@cuanschutz.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Terra Hiller, MSN, RN
Phone
720-602-1438
Email
Terra.Hiller@dhha.org
Facility Information:
Facility Name
Denver Health Medical Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80204
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ivor Douglas, MD
Phone
303-602-5012
Email
ivor.douglas@dhha.org
First Name & Middle Initial & Last Name & Degree
Terra Hiller, RN
Phone
303-602-1438
Email
terra.hiller@dhha.org

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
currently individual participant data will not be made available to other researchers

Learn more about this trial

Micro and Macro Circulation in Sepsis

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