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COVID-19 Associated Endothelial Dysfunction Study (CAUSED)

Primary Purpose

Covid19, Microcirculation

Status

Completed

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

Procedure : Multimodal microvascular assessment at study inclusion

About this trial

This is an interventional diagnostic trial for Covid19

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria :

Adult patient (≥ 18 ans)
Affiliation to the French National Healthcare System
Voluntary patient who have given oral consent

Cohort C1, COVID19 (+) patients hospitalized in ICU :

Patient admitted to ICU within 72 hours before inclusion
Patient presenting SARS-COV2 pneumonia diagnosed by CT scan or by COVID-19 PCR test.

Cohort C2, COVID19 (-) patients hospitalized in ICU :

Patient admitted to ICU within 72 hours before inclusion
All COVID19 PCR tests carried out in the 15 days prior inclusion are negative
All the CT scans possibly performed since the acute event do not show COVID19 pulmonary lesions
Matching with the cases C1 COVID 19 (+) patients on sex, age (threshold at 65 years), treated hypertension, treated diabetes mellitus.

Cohort C3, elective surgery patients who are not hospitalized in ICU :

ASA 1 classification (no major comorbidity, a normaly healthy patient)
Asymptomatic to COVID19 according to French Anesthesiology Society 2020 :
- No major symptoms among : measured fever > 38°C, dry cough, shortness of breath or high respiratory rate (>20/min), anosmia, ageusia
- No more than one minor symptom among : sore throat, rhinorrhea, chest pain, myalgia, general alteration or severe tiredness, confusion, disorientation, headache, diarrhea, nausea or/and vomiting, rash/ frostbite/cracking on fingers or hand
No positive COVID19 PCR test within 15 days prior to inclusion

Non-inclusion criteria :

Proven sepsis (Procalcitonin >1.0 µg/l) in the 24 hours prior to inclusion
End-stage kidney disease with dialysis
Patient with haemodynamic failure treated by norepinephrine
Patient with traumatic brain injury
Intubated patient and/or sedated
Pregnant woman, parturient and nursing mother
Person restricted in liberty by an administrative or judicial decision
Patient concerned with admission for psychiatric care
Adult person subject to a legal protection measure or unable to express consent

Exclusion criteria :

• Cohorts C2 and C3 : positive COVID-19 PCR test within 5 days after inclusion

Sites / Locations

UH Angers
Hopital E.Herriot - Hospices Civils de Lyon

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Arm Label

Cohort C1

Cohort C2

Cohort C3

Arm Description

COVID19 (+) ICU patients with COVID19 pneumonia.

COVID19 (-) matched ICU patients

COVID19 (-) ASA 1 non-hospitalized patients

Outcomes

Primary Outcome Measures

Endothelial function measured by Near-infrared spectroscopy (NIRS)

Measure : Saturation Tissue (StO2) after a vascular occlusion test (VOT)

Secondary Outcome Measures

Endothelial function measured by perfusion index

measure : Perfusion index after a vascular occlusion test (VOT)

Microvascular reactivity measured laser speckle contrast imaging

measure : Vasodilation after iontophoresis of Acetylcholine and Nitroprusside

Morphological analysis by Sublingual videomicroscopy

measure : Microvascular flow index (MFI)

Morphological analysis by Sublingual videomicroscopy

measure : Perfused vessel density (PVD)

Inflammatory status

measure : C-reactive protein level

Inflammatory status

measure : neutrophil to lymphocyte ratio

Prothrombotic condition

measure : D-Dimer Level and

Thrombotic events

measure : All arterial and/or venous thromboembolic events since acute episode

Severity of lung disease

measure : PaO2/FiO2 ratio

Severity of lung disease

measure : percentage of pulmonary lesions assessed by CT scan at the ICU admission.

Mortality

measure : Mortality in ICU

Organ failure

measure : Sequential Organ Failure Assessment (SOFA) Score, minimum value 0 and maximum value 24. The higher score means a worse outcome.

Full Information

NCT ID

NCT04773899

First Posted

February 19, 2021

Last Updated

May 3, 2023

Sponsor

University Hospital, Angers

1. Study Identification

Unique Protocol Identification Number

NCT04773899

Brief Title

COVID-19 Associated Endothelial Dysfunction Study

Acronym

CAUSED

Official Title

L'Étude de la Dysfonction endothéliale Dans la Maladie à COVID-19 Chez Des Patients en Soins Critiques.

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Completed

Study Start Date

October 22, 2021 (Actual)

Primary Completion Date

October 21, 2022 (Actual)

Study Completion Date

December 21, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Angers

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

SARS-CoV-2 enters human cells through the binding of the spike protein with angiotensin converting enzyme-2 (ACE2), a membrane receptor highly expressed in immune or non-immune cells, and in many organs, including lungs and endothelial cells. In COVID-19 disease, the infection of endothelial might cause an acute endothelial dysfunction. The objective of this study is to demonstrate that patients COVID19 (+) hospitalized in ICU present an acute endothelial dysfunction (compared with COVID19 (-) also hospitalized in ICU). This acute endothelial dysfunction could lead to organ failure, systemic immune dysregulation and thrombosis.

Detailed Description

This cohort study compares 3 exposure cohorts : Cohort C1 includes COVID19 (+) patients admitted in ICU in whom the diagnosis of COVID19 pneumonia was confirmed. Cohort C2 includes COVID 19 (-) matched patients also admitted in ICU. Cohort C3 is a control group. Patients with few comorbidities, ASA 1, recruited during preoperative assessment for elective surgery. Eligible patients are included within 72 hours of ICU admission (C1, C2) or during the preoperative assessment (C3). Oral consent is needed after complete explanation of the protocol. During inclusion visit (V0), patient characteristics as treatments, medical history, clinical and biological data are registered. Microcirculation is assessed for each patient directly after inclusion. For patients in C1 and C2 a follow-up is planned. This visit (V1) occurs when the patient is discharged from ICU or the day of his death if it occurs in ICU. In case of prolonged stay in ICU, V1 is carried out 2 months after inclusion. During V1, arterial and/or venous thromboembolic events and mortality in ICU is registered. For Patients in C3, no follow-up is planned.

6. Conditions and Keywords

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

Covid19, Microcirculation

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

75 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort C1

Arm Type

Other

Arm Description

COVID19 (+) ICU patients with COVID19 pneumonia.

Arm Title

Cohort C2

Arm Type

Other

Arm Description

COVID19 (-) matched ICU patients

Arm Title

Cohort C3

Arm Type

Other

Arm Description

COVID19 (-) ASA 1 non-hospitalized patients

Intervention Type

Diagnostic Test

Intervention Name(s)

Procedure : Multimodal microvascular assessment at study inclusion

Intervention Description

Vascular occlusion test (VOT) performed on the arm. Measurement of the quality of tissue reperfusion by NIRS on the thenar eminence and the digital perfusion index. Microcirculation reactivity is measured for each patient with a laser speckle contrast imaging (LSCI) placed on the forearm. Tests will be performed for evaluation of microvascular reactivity: Acetylcholine and Nitroprusside Iontophoresis. Morphological analysis of the microcirculation by sublingual videomicroscopy.

Primary Outcome Measure Information:

Title

Endothelial function measured by Near-infrared spectroscopy (NIRS)

Description

Measure : Saturation Tissue (StO2) after a vascular occlusion test (VOT)

Time Frame

within 72 hours of admission in Intensive Care Unit (ICU)

Secondary Outcome Measure Information:

Title

Endothelial function measured by perfusion index

Description

measure : Perfusion index after a vascular occlusion test (VOT)

Time Frame

within 72 hours of admission in ICU

Title

Microvascular reactivity measured laser speckle contrast imaging

Description

measure : Vasodilation after iontophoresis of Acetylcholine and Nitroprusside

Time Frame

within 72 hours of admission in ICU

Title

Morphological analysis by Sublingual videomicroscopy

Description

measure : Microvascular flow index (MFI)

Time Frame

within 72 hours of admission in ICU

Title

Morphological analysis by Sublingual videomicroscopy

Description

measure : Perfused vessel density (PVD)

Time Frame

within 72 hours of admission in ICU

Title

Inflammatory status

Description

measure : C-reactive protein level

Time Frame

Inclusion

Title

Inflammatory status

Description

measure : neutrophil to lymphocyte ratio

Time Frame

Inclusion

Title

Prothrombotic condition

Description

measure : D-Dimer Level and

Time Frame

Inclusion

Title

Thrombotic events

Description

measure : All arterial and/or venous thromboembolic events since acute episode

Time Frame

Inclusion (V0) up to 8 weeks maximum

Title

Severity of lung disease

Description

measure : PaO2/FiO2 ratio

Time Frame

Inclusion

Title

Severity of lung disease

Description

measure : percentage of pulmonary lesions assessed by CT scan at the ICU admission.

Time Frame

Inclusion

Title

Mortality

Description

measure : Mortality in ICU

Time Frame

Up to 8 weeks after inclusion

Title

Organ failure

Description

measure : Sequential Organ Failure Assessment (SOFA) Score, minimum value 0 and maximum value 24. The higher score means a worse outcome.

Time Frame

Inclusion

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria : Adult patient (≥ 18 ans) Affiliation to the French National Healthcare System Voluntary patient who have given oral consent Cohort C1, COVID19 (+) patients hospitalized in ICU : Patient admitted to ICU within 72 hours before inclusion Patient presenting SARS-COV2 pneumonia diagnosed by CT scan or by COVID-19 PCR test. Cohort C2, COVID19 (-) patients hospitalized in ICU : Patient admitted to ICU within 72 hours before inclusion All COVID19 PCR tests carried out in the 15 days prior inclusion are negative All the CT scans possibly performed since the acute event do not show COVID19 pulmonary lesions Matching with the cases C1 COVID 19 (+) patients on sex, age (threshold at 65 years), treated hypertension, treated diabetes mellitus. Cohort C3, elective surgery patients who are not hospitalized in ICU : ASA 1 classification (no major comorbidity, a normaly healthy patient) Asymptomatic to COVID19 according to French Anesthesiology Society 2020 : No major symptoms among : measured fever > 38°C, dry cough, shortness of breath or high respiratory rate (>20/min), anosmia, ageusia No more than one minor symptom among : sore throat, rhinorrhea, chest pain, myalgia, general alteration or severe tiredness, confusion, disorientation, headache, diarrhea, nausea or/and vomiting, rash/ frostbite/cracking on fingers or hand No positive COVID19 PCR test within 15 days prior to inclusion Non-inclusion criteria : Proven sepsis (Procalcitonin >1.0 µg/l) in the 24 hours prior to inclusion End-stage kidney disease with dialysis Patient with haemodynamic failure treated by norepinephrine Patient with traumatic brain injury Intubated patient and/or sedated Pregnant woman, parturient and nursing mother Person restricted in liberty by an administrative or judicial decision Patient concerned with admission for psychiatric care Adult person subject to a legal protection measure or unable to express consent Exclusion criteria : • Cohorts C2 and C3 : positive COVID-19 PCR test within 5 days after inclusion

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Samir HENNI, MD PhD

Organizational Affiliation

UH Angers

Official's Role

Principal Investigator

Facility Information:

Facility Name

UH Angers

City

Angers

ZIP/Postal Code

49933

Country

France

Facility Name

Hopital E.Herriot - Hospices Civils de Lyon

City

Lyon

ZIP/Postal Code

69437

Country

France

12. IPD Sharing Statement

Plan to Share IPD

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COVID-19 Associated Endothelial Dysfunction Study

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