SepsisDAISYNCT05694455
Micro and Macro Circulation in Sepsis
A study testing Starling Stroke Volume (Starling SV)- Passive Leg Raise, Microscan Sublingual Microscopy and Venous Excess Ultrasound Scoring (VExUS) in people with Sepsis and Septic Shock, run by Denver Health and Hospital Authority at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Sepsis, Septic Shock
- What is being tested?
- Starling Stroke Volume (Starling SV)- Passive Leg Raise, Microscan Sublingual Microscopy and Venous Excess Ultrasound Scoring (VExUS)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2022to 31 May 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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:
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Denver Health Medical Center
Denver, Colorado, 80204
About this study
Official title: Clinical Utility of Longitudinal Measurement of Hemodynamic Incoherence and Endothelial
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 microhemodynamics (MiH) and macro hemodynamics (maH) and the perfused boundary region (PBR, an visual proxy for eGC thickness) using HVM, and a validated circulating biomarker of eGC integrity.
Read the 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 Coronavirus Disease 2019 (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. 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. 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. 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. 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. MiH measures have also been shown to differ significantly between septic patients and healthy controls. 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. 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.
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 Starling Stroke Volume/Non-invasive cardiac monitor (NICOM) testing.
- Conditions
- Sepsis, Septic Shock
- Being tested
- Starling Stroke Volume (Starling SV)- Passive Leg Raise, Microscan Sublingual Microscopy, Venous Excess Ultrasound Scoring (VExUS), Urine Collection
- Medical subject headings
- Sepsis, Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Starling Stroke Volume (Starling SV)- Passive Leg RaiseDiagnostic test
Also called Baxter Starling Stroke Volume (SV)
All septic patients will have a passive leg raise performed with the assistance of an Starling SV device to look at Stroke Volume change. This will be performed at admission and 4 hours after admission. This intervention will not be performed on healthy controls
Microscan Sublingual MicroscopyDiagnostic test
Also called Microvision Sublingual Microscopy
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 performed 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.
Venous Excess Ultrasound Scoring (VExUS)Diagnostic test
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 Inferior Vena Cava diameter, hepatic vein, portal vein, renal veins and scored using the Venous Excess Ultrasound (VExUS scale). Healthy controls will not have ultrasound performed
Urine CollectionOther
The urine assay is collected passively from the patient will be ran through a Dimethylmethylene blue (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.
| Study group | Role | What they receive |
|---|---|---|
| Septic Patient Interventions | Other | Septic Patients will have all interventions performed: Urine collection, Passive Leg Raise, Ultrasound and sublingual microscopy Receives: Diagnostic Test: Starling Stroke Volume (Starling SV)- Passive Leg Raise; Diagnostic Test: Microscan Sublingual Microscopy; Diagnostic Test: Venous Excess Ultrasound Scoring (VExUS); Other: Urine Collection |
| Control Patient Interventions | Other | Control patients will have urine collection and sublingual microscopy performed when intubated Receives: Diagnostic Test: Starling Stroke Volume (Starling SV)- Passive Leg Raise; Other: Urine Collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Initiation and Duration Renal Replacement Therapy
Renal Replacement Therapy will be monitored while hospitalized for Sepsis/Septic Shock for initiation and days receiving Renal replacement will be counted.
Measured: 90 day
Secondary outcomes (2)
Rate of Inpatient Mortality
Patient Death while hospitalized for the admission of Sepsis/Septic Shock
Measured: 90 day
Rate of 90 day survival
Patient death within 90 days of admission to the hospital for Sepsis/Septic Shock
Measured: 90 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2023
- Study start1 Jul 2022
- Primary completion31 May 2025
- Study completion31 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- 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 micro hemodynamic incoherence and Macro hemodynamic incoherence as well as the total amount of IV fluids and vasoactive medications administered, demographics, Charlson morbidity scale and Sofa score. Healthy controls will have sublingual microscopy and urine collection performed at time of intubation for elective procedure.
- Masking
- None (open label)
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Denver Health and Hospital Authority
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Ivor Douglas, Denver Health and Hospital Authority
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05694455
- Sponsor's protocol ID
- 22-0349
- Acronym
- DAISY
- Status last verified
- Dec 2025
- First submitted
- 5 Jan 2023
- Last updated
- 5 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No: currently individual participant data will not be made available to other researchers
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Utility of Longitudinal Measurement of Hemodynamic Incoherence and Endothelial
- ClinicalTrials.gov ID
- NCT05694455
- Acronym / sponsor ID
- DAISY / 22-0349
- Conditions
- Sepsis, Septic Shock
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Denver Health and Hospital AuthorityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- 1 Jul 2022 (actual)
- Primary completion
- 31 May 2025 (actual)
- Study completion
- 31 May 2025 (actual)
- First posted
- 23 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 microhemodynamics (MiH) and macro hemodynamics (maH) 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 Coronavirus Disease 2019 (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. 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. 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. 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. 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. MiH measures have also been shown to differ significantly between septic patients and healthy controls. 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. 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.
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 Starling Stroke Volume/Non-invasive cardiac monitor (NICOM) testing.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- 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 micro hemodynamic incoherence and Macro hemodynamic incoherence as well as the total amount of IV fluids and vasoactive medications administered, demographics, Charlson morbidity scale and Sofa score. Healthy controls will have sublingual microscopy and urine collection performed at time of intubation for elective procedure.
| Arm | Type | Receives |
|---|---|---|
| Septic Patient Interventions | Other | Diagnostic Test: Starling Stroke Volume (Starling SV)- Passive Leg Raise, Diagnostic Test: Microscan Sublingual Microscopy, Diagnostic Test: Venous Excess Ultrasound Scoring (VExUS), Other: Urine CollectionSeptic Patients will have all interventions performed: Urine collection, Passive Leg Raise, Ultrasound and sublingual microscopy |
| Control Patient Interventions | Other | Diagnostic Test: Starling Stroke Volume (Starling SV)- Passive Leg Raise, Other: Urine CollectionControl patients will have urine collection and sublingual microscopy performed when intubated |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Greater than or equal to 18 years of age
- Diagnosed with sepsis or septic shock
- Require admission to the Hospital
- Greater than or equal to 18 years of age
- Undergoing elective surgery requiring intubation and general anesthesia
Key exclusion criteria (10 listed)
- Patients with any of the following characteristics will be excluded
- Less than 18 years old
- Chronic Kidney disease on dialysis
- Currently pregnant
- Incarcerated persons
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Starling Stroke Volume (Starling SV)- Passive Leg RaiseAlso: Baxter Starling Stroke Volume (SV)All septic patients will have a passive leg raise performed with the assistance of an Starling SV device to look at Stroke Volume change. This will be performed at admission and 4 hours after admission. This intervention will not be performed on healthy controls | Diagnostic test | Control Patient Interventions, Septic Patient Interventions |
| Microscan Sublingual MicroscopyAlso: Microvision Sublingual MicroscopyAll 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 performed 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. | Diagnostic test | Septic Patient Interventions |
| Venous Excess Ultrasound Scoring (VExUS)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 Inferior Vena Cava diameter, hepatic vein, portal vein, renal veins and scored using the Venous Excess Ultrasound (VExUS scale). Healthy controls will not have ultrasound performed | Diagnostic test | Septic Patient Interventions |
| Urine CollectionThe urine assay is collected passively from the patient will be ran through a Dimethylmethylene blue (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. | Other | Control Patient Interventions, Septic Patient Interventions |
Primary outcome
Initiation and Duration Renal Replacement Therapy
Time frame: 90 day
Renal Replacement Therapy will be monitored while hospitalized for Sepsis/Septic Shock for initiation and days receiving Renal replacement will be counted.
2 secondary outcomes
Rate of Inpatient Mortality
Time frame: 90 day
Rate of 90 day survival
Time frame: 90 day
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2025.
- Individual participant dataSharing planned: No. currently individual participant data will not be made available to other researchers
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Starling Stroke Volume (Starling SV)- Passive Leg Raise, Microscan Sublingual Microscopy and Venous Excess Ultrasound Scoring (VExUS) in people with Sepsis and Septic Shock, run by Denver Health and Hospital Authority at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Initiation and Duration Renal Replacement Therapy (time frame: 90 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2025; AzTrials last refreshed its copy on 30 Oct 2026.