MIcrovascular Dysfunction in CRitically Ill cOVID-19 Patients

NCT ID: NCT04819802

Last Updated: 2021-04-01

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 40 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-03-28
• Study Completion Date: 2022-10-31

Brief 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 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.

Conditions

Covid-19; Critical Illness; Hemodynamics; SARS-CoV Infection

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Covid-19 patients

Adult Covid-19 patients admitted to intensive care units

Measurement of sublingual microcirculation

Intervention Type: OTHER

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 sampling

Intervention Type: OTHER

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.

Interventions

Measurement of sublingual microcirculation

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.

Intervention Type: OTHER

Plasma sampling

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• Lesions of the oral mucosa

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jacques Duranteau, MD, PhD

Role: STUDY_DIRECTOR

APHP, Kremlin Bicêtre Hospital

Locations

Surgical Intensive Care Unit - Kremlin Bicêtre Hospital, APHP

Le Kremlin-Bicêtre, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Benjamin Bergis, MD

Role: CONTACT

benjamin.bergis@aphp.fr

+33145212367

Anatole Harrois, MD, PhD

Role: CONTACT

Anatole.harrois@aphp.fr

Facility Contacts

Benjamin Bergis, MD

Role: primary

benjamin.bergis@aphp.fr

+33145212367

Other Identifiers

2021-A00321-40

Identifier Type: OTHER

Identifier Source: secondary_id

APHP210249

Identifier Type: -

Identifier Source: org_study_id