Covid-19MICROVIDNCT04819802
MIcrovascular Dysfunction in CRitically Ill cOVID-19 Patients
An observational study of Covid-19 and Critical Illness, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Microcirculatory dysfunction appears to play a key role in the development of organ failure leading to the death of patients with coronavirus disease 2019 (Covid-19). It is still uncertain today whether this damage is secondary to direct viral infection of endothelial cells or the consequence of the inappropriate… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid-19, Critical Illness, Hemodynamics
- What is being tested?
- Measurement of sublingual microcirculation and Plasma sampling
- How many people
- 40 participants
- Where
- 1 siteFrance
- Study dates
- 28 Mar 2021to Oct 2022
- Phase
- Observational
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adult patients admitted to ICU for COVID-19
Who may be able to join
- Adult patient (≥ 18 ans)
- Affiliation to the French social security system
- Patient admitted to ICU within 72 hours before inclusion
- Patient presenting SARS-CoV-2 pneumonia diagnosed by CT scan or by COVID-19 PCR test
Who cannot join
- Lesions of the oral mucosa
Trial locations and contacts
1 site in 1 country.
Anatole Harrois, MD, PhD contact
France1 site, 1 recruiting
- Recruiting
Surgical Intensive Care Unit - Kremlin Bicêtre Hospital, APHP
Le Kremlin-Bicêtre, 94270
Benjamin Bergis, MD, +33145212367, benjamin.bergis@aphp.fr
About this study
Official title: Microvascular Flow Alteration and Endothelial Dysfunction in Critically Ill Patient With Covid-19
Microcirculatory dysfunction appears to play a key role in the development of organ failure leading to the death of patients with coronavirus disease 2019 (Covid-19). It is still uncertain today whether this damage is secondary to direct viral infection of endothelial cells or the consequence of the inappropriate inflammatory response induced by the infection. The analysis of endothelial and microcirculatory dysfunctions and glycocalyx degradation therefore appears to be necessary in the understanding of the pathophysiological mechanisms of Covid sepsis and could play a role in the evaluation of the efficacy of certain therapeutics which would aim at improving regional perfusion by decreasing microcirculatory dysfunction.However, the analysis of microcirculatory failure, endothelial dysfunction and glycocalyx degradation has so far only been evaluated in small cohorts, without quantitative analysis of microcirculatory perfusion
Read the detailed description
The study of pathophysiological mechanisms of cellular penetration of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) allows the understanding of organ failures observed in COVID 19. In order to allow its fusion with the cell membrane, SARS-Cov-2 must bind the Angiotensin Converting Enzyme 2 (ACE2) via its Spike protein. This process requires the priming of the viral S protein by a cellular serine protease TMPRSS2. Thus, any cell co-expressing these two receptors is a potential target for the virus. Among all the cells for which this co-expression could be observed, endothelial cells and vascular pericytes seem to be potential targets, whose infection could lead to the development of an endothelial dysfunction responsible for microcirculatory dysfunction. In addition, inappropriate host immune system response observed in Covid-19 with massive production of pro-inflammatory cytokines as IL-6, TNF α and VEGF could lead to endothelial dysfunction through neutrophils, monocytes and macrophages mobilization producing Reactive Oxygen Species that increase endothelium and glycocalyx damages. The resulting pro-adhesive, pro-vasoconstricting and prothrombotic effects could lead to vascular micro-thrombosis, capillary plugging and impairment of capillary flow.
Whether endothelial dysfunction is caused by direct viral cell infection or pro-inflammatory response is uncertain, but various studies have confirmed that endotheliopathy plays a key role in pathophysiological mechanisms in Covid 19.
In the context of critical care, the evaluation of microcirculatory perfusion appears to be a diagnostic tool of major importance. Indeed, microcirculatory dysfunction is directly associated with increased organ failure and mortality in the ICU. In addition, many clinical situations such as sepsis or hemorrhagic shock may be responsible for a loss of hemodynamic coherence between macro and microcirculatory parameters. Thus, the correction of macrohemodynamic parameters (arterial pressure, cardiac output, plasma lactate, central venous oxygen saturation) may be associated with persistent microcirculatory hypoperfusion. It thus appears essential to develop systems for assessing the microcirculation in order to move towards resuscitation guided by microcirculatory objectives.
The aim of this study is to describe the sublingual microcirculation and to evaluate endothelial dysfunction in critically ill patient with Covid-19, and to determine whether there is a correlation between the severity of microcirculatory damage, endothelial dysfunction and clinically important outcomes in ICU. The data will serve to develop strategies for individualized management of high-risk patients screened with microcirculation evaluation.
- Conditions
- Covid-19, Critical Illness, Hemodynamics, SARS-CoV Infection
- Being tested
- Measurement of sublingual microcirculation, Plasma sampling
- Keywords
- Covid-19, Covid-19 / Pathophysiology, Covid-19 / Virology, Critical illness, Hemodynamics, Intensive Care Units, Microcirculation, Microcirculation / Physiology, Microvessels / Physiopathology, Capillary permeability, Prospective Studies, SARS-CoV-2, SARS-CoV-2 / physiology, Biomarkers / Blood, Glycocalyx / metabolism, Glycocalyx / Pathology, Regional blood flow, Mouth mucosa / Blood supply, Syndecan-1 / Blood, Organ dysfunction scores
- Medical subject headings
- COVID-19, Critical Illness, Severe Acute Respiratory Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Measurement of sublingual microcirculationOther
Sublingual microcirculation will be evaluated using a MicroScan (Microvision Medical, Amsterdam, the Netherlands) incident dark field imaging device. Perfusion measurements will be taken once a day during the first three days after inclusion (i.e. three measurement times). At each measurement time, five sequences of 20 secs will be recorded at five different sites. The video clips will be secondarily analyzed by a trained, blind investigator.
Plasma samplingOther
Additional volume during blood draw to assess plasma levels of the following endothelial markers: syndecan-1, angiopoietin-2, vascular endothelial growth factor-A (VEGF-A), thrombomodulin.
| Study group | Role | What they receive |
|---|---|---|
| Covid-19 patients | Adult Covid-19 patients admitted to intensive care units Receives: Other: Measurement of sublingual microcirculation; Other: Plasma sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Microvascular flow index (MFI)
Change in a semi quantitative score evaluating the sublingual microcirculation using an incident dark field imaging device (Microscan, MicroVision Medical ) over the first days of ICU stay
Measured: At admission, on day 1 and day 2
Secondary outcomes (16)
Change in perfused vessel density
Change in sublingual microcirculation over the first days of ICU stay as assessed by perfused vessel density evaluation
Measured: At admission, on day 1 and day 2
Change in plasma Syndecan-1 levels (in pg/ml)
Change in the levels of endothelium biomarker Syndecan-1 over the first days of ICU stay
Measured: At admission, on day 1 and day 2
Change in plasma Thrombomodulin levels (in arbitrary units/ml)
Change in the levels of endothelium biomarker Thrombomodulin over the first days of ICU stay
Measured: At admission, on day 1 and day 2
Change in plasma VEGF-A levels (in arbitrary units/ml)
Change in the levels of endothelium biomarker VEGF-A over the first days of ICU stay
Measured: At admission, on day 1 and day 2
Change in plasma Angiopoietin-2 levels (in ng/ml)
Change in the levels of endothelium biomarker Angiopoietin-2 over the first days of ICU stay
Measured: At admission, on day 1 and day 2
Change in cardiac output
Change in cardiac output (in ml/min) measured by transthoracic echocardiography over the first days in ICU stay
Measured: At admission, on day 1 and day 2
Blood D-dimer levels (in µg/l)
D-dimer level measurement to evaluate the prothrombotic condition
Measured: At admission
Neutrophil to Lymphocyte ratio
Neutrophil to Lymphocyte ratio measurement to evaluate the proinflammatory status
Measured: At admission
Blood C Reactive Protein levels (in mg/l)
C Reactive Protein levels measurement to evaluate the proinflammatory status
Measured: At admission
The ratio of arterial oxygen partial pressure (PaO2) to fractional inspired oxygen (FiO2)
PaO2/FiO2 ratio measurement to evaluate the severity of lung disease
Measured: At admission
The percentage of pulmonary lesions as assessed by computerized tomography (CT) scan
The percentage of pulmonary lesions as assessed by CT scan to evaluate the severity of lung disease at ICU admission
Measured: At admission
Mortality
Mortality rate in the ICU
Measured: Day 28
Invasive Mechanical ventilation
Number of days under invasive Mechanical ventilation in the ICU
Measured: Day 28
Length of stay in the ICU
Number of days of hospitalization in the ICU
Measured: Day 28
Acute kidney injury
Occurrence of acute kidney injury using KDIGO definition during the ICU stay
Measured: Day 28
Organ failure
Change in Sequential Organ Failure Assessment (SOFA) Score during the ICU stay (minimum value 0; maximum value 24; the higher score means a worst outcome).
Measured: Every day from Day 0 to Day 8, and at Day 28 after inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2021
- Study start28 Mar 2021
- Primary completionApr 2022 (estimated)
- Study completionOct 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Covid-19Studies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jacques Duranteau, MD, PhD, Study director, APHP, Kremlin Bicêtre Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04819802
- Sponsor's protocol ID
- APHP210249
- Other IDs
- 2021-A00321-40
- Acronym
- MICROVID
- Status last verified
- Mar 2021
- First submitted
- 26 Mar 2021
- Last updated
- 1 Apr 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Microvascular Flow Alteration and Endothelial Dysfunction in Critically Ill Patient With Covid-19
- ClinicalTrials.gov ID
- NCT04819802
- Acronym / sponsor ID
- MICROVID / APHP210249
- Conditions
- Covid-19, Critical Illness, Hemodynamics, SARS-CoV Infection
- Keywords
- Covid-19, Covid-19 / Pathophysiology, Covid-19 / Virology, Critical illness, Hemodynamics, Intensive Care Units, Microcirculation, Microcirculation / Physiology
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 28 Mar 2021 (actual)
- Primary completion
- Apr 2022 (estimated)
- Study completion
- Oct 2022 (estimated)
- First posted
- 29 Mar 2021 (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.
Microcirculatory dysfunction appears to play a key role in the development of organ failure leading to the death of patients with coronavirus disease 2019 (Covid-19). It is still uncertain today whether this damage is secondary to direct viral infection of endothelial cells or the consequence of the inappropriate inflammatory response induced by the infection. The analysis of endothelial and microcirculatory dysfunctions and glycocalyx degradation therefore appears to be necessary in the understanding of the pathophysiological mechanisms of Covid sepsis and could play a role in the evaluation of the efficacy of certain therapeutics which would aim at improving regional perfusion by decreasing microcirculatory dysfunction.However, the analysis of microcirculatory failure, endothelial dysfunction and glycocalyx degradation has so far only been evaluated in small cohorts, without quantitative analysis of microcirculatory perfusion
Detailed description
The study of pathophysiological mechanisms of cellular penetration of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) allows the understanding of organ failures observed in COVID 19. In order to allow its fusion with the cell membrane, SARS-Cov-2 must bind the Angiotensin Converting Enzyme 2 (ACE2) via its Spike protein. This process requires the priming of the viral S protein by a cellular serine protease TMPRSS2. Thus, any cell co-expressing these two receptors is a potential target for the virus. Among all the cells for which this co-expression could be observed, endothelial cells and vascular pericytes seem to be potential targets, whose infection could lead to the development of an endothelial dysfunction responsible for microcirculatory dysfunction. In addition, inappropriate host immune system response observed in Covid-19 with massive production of pro-inflammatory cytokines as IL-6, TNF α and VEGF could lead to endothelial dysfunction through neutrophils, monocytes and macrophages mobilization producing Reactive Oxygen Species that increase endothelium and glycocalyx damages. The resulting pro-adhesive, pro-vasoconstricting and prothrombotic effects could lead to vascular micro-thrombosis, capillary plugging and impairment of capillary flow.
Whether endothelial dysfunction is caused by direct viral cell infection or pro-inflammatory response is uncertain, but various studies have confirmed that endotheliopathy plays a key role in pathophysiological mechanisms in Covid 19.
In the context of critical care, the evaluation of microcirculatory perfusion appears to be a diagnostic tool of major importance. Indeed, microcirculatory dysfunction is directly associated with increased organ failure and mortality in the ICU. In addition, many clinical situations such as sepsis or hemorrhagic shock may be responsible for a loss of hemodynamic coherence between macro and microcirculatory parameters. Thus, the correction of macrohemodynamic parameters (arterial pressure, cardiac output, plasma lactate, central venous oxygen saturation) may be associated with persistent microcirculatory hypoperfusion. It thus appears essential to develop systems for assessing the microcirculation in order to move towards resuscitation guided by microcirculatory objectives.
The aim of this study is to describe the sublingual microcirculation and to evaluate endothelial dysfunction in critically ill patient with Covid-19, and to determine whether there is a correlation between the severity of microcirculatory damage, endothelial dysfunction and clinically important outcomes in ICU. The data will serve to develop strategies for individualized management of high-risk patients screened with microcirculation evaluation.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Covid-19 patients | – | Other: Measurement of sublingual microcirculation, Other: Plasma samplingAdult Covid-19 patients admitted to intensive care units |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult patients admitted to ICU for COVID-19
Key inclusion criteria (4 listed)
- Adult patient (≥ 18 ans)
- Affiliation to the French social security system
- Patient admitted to ICU within 72 hours before inclusion
- Patient presenting SARS-CoV-2 pneumonia diagnosed by CT scan or by COVID-19 PCR test
Key exclusion criteria (1 listed)
- Lesions of the oral mucosa
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 |
|---|---|---|
| Measurement of sublingual microcirculationSublingual microcirculation will be evaluated using a MicroScan (Microvision Medical, Amsterdam, the Netherlands) incident dark field imaging device. Perfusion measurements will be taken once a day during the first three days after inclusion (i.e. three measurement times). At each measurement time, five sequences of 20 secs will be recorded at five different sites. The video clips will be secondarily analyzed by a trained, blind investigator. | Other | Covid-19 patients |
| Plasma samplingAdditional volume during blood draw to assess plasma levels of the following endothelial markers: syndecan-1, angiopoietin-2, vascular endothelial growth factor-A (VEGF-A), thrombomodulin. | Other | Covid-19 patients |
Primary outcome
Change in Microvascular flow index (MFI)
Time frame: At admission, on day 1 and day 2
Change in a semi quantitative score evaluating the sublingual microcirculation using an incident dark field imaging device (Microscan, MicroVision Medical ) over the first days of ICU stay
16 secondary outcomes
Change in perfused vessel density
Time frame: At admission, on day 1 and day 2
Change in plasma Syndecan-1 levels (in pg/ml)
Time frame: At admission, on day 1 and day 2
Change in plasma Thrombomodulin levels (in arbitrary units/ml)
Time frame: At admission, on day 1 and day 2
Change in plasma VEGF-A levels (in arbitrary units/ml)
Time frame: At admission, on day 1 and day 2
Change in plasma Angiopoietin-2 levels (in ng/ml)
Time frame: At admission, on day 1 and day 2
Change in cardiac output
Time frame: At admission, on day 1 and day 2
Blood D-dimer levels (in µg/l)
Time frame: At admission
Neutrophil to Lymphocyte ratio
Time frame: At admission
Blood C Reactive Protein levels (in mg/l)
Time frame: At admission
The ratio of arterial oxygen partial pressure (PaO2) to fractional inspired oxygen (FiO2)
Time frame: At admission
The percentage of pulmonary lesions as assessed by computerized tomography (CT) scan
Time frame: At admission
Mortality
Time frame: Day 28
Invasive Mechanical ventilation
Time frame: Day 28
Length of stay in the ICU
Time frame: Day 28
Acute kidney injury
Time frame: Day 28
Organ failure
Time frame: Every day from Day 0 to Day 8, and at Day 28 after inclusion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2021.
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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.
Anatole Harrois, MD, PhD contact
Jacques Duranteau, MD, PhD study director
APHP, Kremlin Bicêtre Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Covid-19 and Critical Illness, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 4 inclusion and 1 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: status not confirmed, as of the sponsor's last update on 1 Apr 2021. 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 France. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Benjamin Bergis, MD (+33145212367, benjamin.bergis@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Microvascular flow index (MFI) (time frame: At admission, on day 1 and day 2). 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 1 Apr 2021.