Biomarkers for Dexamethasone Response in Sars-Cov-2 / COVID-19 Pneumonia

N/ATerminatedNCT04619693

University Hospital, Montpellier79 enrolled

Overview

The primary objective of this study is to demonstrate (at the time of admission) biomarkers of interest (Human Plasma BAK125 panel + interferon panel) for dexamethasone responders versus non-responders in SARS-CoV-2 hypoxemic pneumonia. The secondary objectives are to describe and compare between groups: * The number of days without mechanical ventilation * The need for mechanical ventilation * 28-day mortality * Progression towards acute respiratory distress syndrome (ARDS) * Change in the qSOFA score * Length of hospitalization * The change in the extent of lesions on thoracic computed tomography scan between inclusion and D7 (or the day of discharge from hospital if \<D7) * Change in biomarkers on D0, D2, D4, D7 (NFS, liver tests (ASAT, ALAT), Creatinine, Albumin, CRP, D-dimers, Ferritin, LDH, lymphocyte phenotyping) * Demonstrate other biomarkers of interest from the usual management (NFS, liver function tests (ASAT, ALAT), Creatinine, Albumin, CRP, D-dimers, Ferritin, LDH, lymphocyte phenotyping) * Change in biomarkers evaluated by mass spectrometry (on a blood sample) on D0 and D7 +/- 2 days * The initial viral load (within 48 hours preceding D0) and at D7 of inclusion estimated from the nasopharyngeal SARS-CoV-2 RT-PCR * Initial SARS-CoV-2 serology and on D7 from inclusion * The A38G polymorphism of the gene coding for Club Cell Secretory Protein (CCSP) for each patient * Short-term complications related to corticosteroid therapy * The quantitative and qualitative impact of corticosteroid therapy on lymphocytes from patients with COVID-19.

This is a prospective multicenter cohort of patients treated with the usual standard of care including systemic corticosteroid therapy with dexamethasone 6 mg / day. INCLUSION (D0): The patients are examined on the day of their hospital admission. After an initial eligibility check and if interest is expressed by the patient, a specific inclusion visit is carried out. FOLLOW-UP: Patients are clinically evaluated at least twice a day (Clinical examination, SpO2, vital signs) during hospitalization. Chest computed tomography and SARS-CoV-2 serology are performed on D0. Viral load is evaluated by the polymerase chain reaction which allowed the diagnosis of covid-19 in the 48 hours preceding D0 and on D7. The evaluation of conventional biomarkers of interest (blood count, hepatic assessment (ASAT, ALAT), serum creatinine, albuminemia, CRP, D-Dimers, LDH, Ferritin) are carried out on D0 (before the 1st dose of corticosteroids), D2 , J4 and J7. The evaluation of biomarkers of interest evaluated by mass spectrometry is carried out on D0 and D7 +/- 2 days. A follow-up call on D28 is carried out (telephone call, collection of vital status and hospitalizations).

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Hospitalization for SARS-COV-2 pneumonia * SARS-COV-2 infection proven by polymerase chain reaction (Nasopharyngeal or other respiratory sampling (expectoration, tracheal aspiration, bronchoalveolar lavage fluid) * Presence of at least one of the following clinical signs of infectious pneumonia: fever (\>38°C), cough, dyspnoea, thoracic pain, crackling/rales * Presence of at least one of the following on a lung computed tomography scan performed within two days of inclusion/randomisation: uni- or bilateral ground glass opacities, consolidations, alveolar condensations, inter- or intra-lobular reticulations, crazy paving * Indication for dexamethasone corticotherapy (defined by the presence of hypoxemia with room-air SpO2 \<94% or a requirement for oxygen therapy to maintain Sp02 \>94%) Exclusion Criteria: * Systemic long-term anti-inflammatory treatment (corticosteroids or anti-interleukins) for chronic disease * Systemic corticosteroid treatment in the 15 days preceding the eligibility visit (for disease other than COVID-19) * Systemic corticosteroid treatment for COVID-19 started more than 48h before the eligibility visit * Absolute contraindication for systemic corticosteroid treatment * Aside from the current acute episode, life expectancy of \<6 months * Patient unable to comply with all study procedures (e.g. contraindication for thoracic scans or bloodwork) * Protected populations according to the French public health code (Pregnant, parturient or lactating women; adults under any form of guardianship; prisoners or persons under any form of judicial protection) * Potential interference from other studies (Participation in any clinical trial of an investigational agent or procedure within one month prior to screening or during the study; exclusion period determined by another study.) * It is impossible to correctly inform the patient (e.g. language barrier) * Absence of free, informed and written consent signed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research) * Non-beneficiary of the French social security, single-payer health insurance system

Outcomes

Primary Outcomes

Treatment failure (yes/no)

Treatment failure is defined as the need to transfer the patient to intensive care for mechanical ventilation.

Time frame: Hospital discharge (expected maximum of 28 days)

Secondary Outcomes

Human Plasma BAK-125 proteomics profile

PeptiQuantTM Plus, Human Plasma BAK 125, Cambridge Isotope Laboratories, Inc

Time frame: Baseline (day 0)

Human Plasma BAK-125 proteomics profile

PeptiQuantTM Plus, Human Plasma BAK 125, Cambridge Isotope Laboratories, Inc

Time frame: Day 7

Circulating blood interferon level

Time frame: Baseline (day 0)

Circulating blood interferon level

Time frame: Day 7

A vector of repeated measures of SpO2

Measured at least twice per day throughout the initial hospitalization period.

Time frame: Throughout initial hospitalization (expected maximum of 28 days)

A vector of repeated measures of FiO2

Measured at least twice per day throughout the initial hospitalization period.

Time frame: Throughout initial hospitalization (expected maximum of 28 days)

A vector of repeated measures of temperature (°C)

Measured at least twice per day throughout the initial hospitalization period.

Time frame: Throughout initial hospitalization (expected maximum of 28 days)

A vector of repeated measures of respiratory rate (cycles per minute)

Measured at least twice per day throughout the initial hospitalization period.

Time frame: Throughout initial hospitalization (expected maximum of 28 days)

A vector of repeated measures of pulse (bpm)

Measured at least twice per day throughout the initial hospitalization period.

Time frame: Throughout initial hospitalization (expected maximum of 28 days)

A vector of repeated measures of systolic blood pressure (mmHg)

Measured at least twice per day throughout the initial hospitalization period.

Time frame: Throughout initial hospitalization (expected maximum of 28 days)

A vector of repeated measures of diastolic blood pressure (mmHg)

Measured at least twice per day throughout the initial hospitalization period.

Time frame: Throughout initial hospitalization (expected maximum of 28 days)

A vector of repeated measures of capillary glycemia (g/L)

Capillary glycemia will be measured at least twice per day throughout the initial hospitalization period.

Time frame: Throughout initial hospitalization (expected maximum of 28 days)

A vector of repeated measures of the qSOFA score

The Quick Sequential Organ Failure Assessment (qSOFA) score will be assessed at least twice per day throughout the initial hospitalization period. The quick Sepsis-related organ failure assessment (qSOFA) score ranges from 0 to 3 points, with '3' indicating the worst health state. It uses three criteria, assigning one point for low blood pressure (systolic blood pressure ≤100 mmHg), high respiratory rate (≥22 breaths per min), or altered mentation.

Time frame: Throughout initial hospitalization (expected maximum of 28 days)

Hemoglobin

Time frame: Baseline (day 0)

Hemoglobin

Time frame: Day 2

Hemoglobin

Time frame: Day 4

Hemoglobin

Time frame: Day 7 (or day of discharge if before day 7)

Platelet count

Time frame: Baseline (day 0)

Platelet count

Time frame: Day 2

Platelet count

Time frame: Day 4

Platelet count

Time frame: Day 7 (or day of discharge if before day 7)

White blood cell count

Time frame: Baseline (day 0)

White blood cell count

Time frame: Day 2

White blood cell count

Time frame: Day 4

White blood cell count

Time frame: Day 7 (or day of discharge if before day 7)

Neutrophil percentage

Time frame: Baseline (day 0)

Neutrophil percentage

Time frame: Day 2

Neutrophil percentage

Time frame: Day 4

Neutrophil percentage

Time frame: Day 7 (or day of discharge if before day 7)

Eosinophil percentage

Time frame: Baseline (day 0)

Eosinophil percentage

Time frame: Day 2

Eosinophil percentage

Time frame: Day 4

Eosinophil percentage

Time frame: Day 7 (or day of discharge if before day 7)

Basophil percentage

Time frame: Baseline (day 0)

Basophil percentage

Time frame: Day 2

Basophil percentage

Time frame: Day 4

Basophil percentage

Time frame: Day 7 (or day of discharge if before day 7)

Lymphocyte percentage

Time frame: Baseline (day 0)

Lymphocyte percentage

Time frame: Day 2

Lymphocyte percentage

Time frame: Day 4

Lymphocyte percentage

Time frame: Day 7 (or day of discharge if before day 7)

Monocyte percentage

Time frame: Baseline (day 0)

Monocyte percentage

Time frame: Day 2

Monocyte percentage

Time frame: Day 4

Monocyte percentage

Time frame: Day 7 (or day of discharge if before day 7)

Prothrombin rate (%)

Time frame: Baseline (day 0)

Prothrombin rate (%)

Time frame: Day 2

Prothrombin rate (%)

Time frame: Day 4

Prothrombin rate (%)

Time frame: Day 7 (or day of discharge if before day 7)

Activated partial thromboplastin time ratio

Time frame: Baseline (Day 0)

Activated partial thromboplastin time ratio

Time frame: Day 2

Activated partial thromboplastin time ratio

Time frame: Day 4

Activated partial thromboplastin time ratio

Time frame: Day 7 (or day of discharge if before day 7)

Fibrinogen (g/L)

Time frame: Baseline (Day 0)

Fibrinogen (g/L)

Time frame: Day 2

Fibrinogen (g/L)

Time frame: Day 4

Fibrinogen (g/L)

Time frame: Day 7 (or day of discharge if before day 7)

D-Dimers (μg/mL)

Time frame: Baseline (Day 0)

D-Dimers (μg/mL)

Time frame: Day 2

D-Dimers (μg/mL)

Time frame: Day 4

D-Dimers (μg/mL)

Time frame: Day 7 (or day of discharge if before day 7)

Aspartate aminotransferase (ASAT; UI/L)

Time frame: Baseline (Day 0)

Aspartate aminotransferase (ASAT; UI/L)

Time frame: Day 2

Aspartate aminotransferase (ASAT; UI/L)

Time frame: Day 4

Aspartate aminotransferase (ASAT; UI/L)

Time frame: Day 7 (or day of discharge if before day 7)

Alanine aminotransferase (ALAT; UI/L)

Time frame: Baseline (Day 0)

Alanine aminotransferase (ALAT; UI/L)

Time frame: Day 2

Alanine aminotransferase (ALAT; UI/L)

Time frame: Day 4

Alanine aminotransferase (ALAT; UI/L)

Time frame: Day 7 (or day of discharge if before day 7)

Glucose (mmol/L)

Time frame: Baseline (Day 0)

Glucose (mmol/L)

Time frame: Day 2

Glucose (mmol/L)

Time frame: Day 4

Glucose (mmol/L)

Time frame: Day 7 (or day of discharge if before day 7)

Glycated haemoglobin (HbA1c; %)

Time frame: Baseline (Day 0)

Glycated haemoglobin (HbA1c; %)

Time frame: Day 2

Glycated haemoglobin (HbA1c; %)

Time frame: Day 4

Glycated haemoglobin (HbA1c; %)

Time frame: Day 7 (or day of discharge if before day 7)

Urea (mmol/L)

Time frame: Baseline (Day 0)

Urea (mmol/L)

Time frame: Day 2

Urea (mmol/L)

Time frame: Day 4

Urea (mmol/L)

Time frame: Day 7 (or day of discharge if before day 7)

Creatinine (µmol/L)

Time frame: Baseline (Day 0)

Creatinine (µmol/L)

Time frame: Day 2

Creatinine (µmol/L)

Time frame: Day 4

Creatinine (µmol/L)

Time frame: Day 7 (or day of discharge if before day 7)

Estimated glomerular filtration rate (eGFR, ml/min/1.73m^2)

Time frame: Baseline (Day 0)

Estimated glomerular filtration rate (eGFR, ml/min/1.73m^2)

Time frame: Day 2

Estimated glomerular filtration rate (eGFR, ml/min/1.73m^2)

Time frame: Day 4

Estimated glomerular filtration rate (eGFR, ml/min/1.73m^2)

Time frame: Day 7 (or day of discharge if before day 7)

Albumin (g/L)

Time frame: Baseline (Day 0)

Albumin (g/L)

Time frame: Day 2

Albumin (g/L)

Time frame: Day 4

Albumin (g/L)

Time frame: Day 7 (or day of discharge if before day 7)

C reactive protein (CRP, mg/L)

Time frame: Baseline (Day 0)

C reactive protein (CRP, mg/L)

Time frame: Day 2

C reactive protein (CRP, mg/L)

Time frame: Day 4

C reactive protein (CRP, mg/L)

Time frame: Day 7 (or day of discharge if before day 7)

Lactate dehydrogenase (LDH, UI/L)

Time frame: Baseline (Day 0)

Lactate dehydrogenase (LDH, UI/L)

Time frame: Day 2

Lactate dehydrogenase (LDH, UI/L)

Time frame: Day 4

Lactate dehydrogenase (LDH, UI/L)

Time frame: Day 7 (or day of discharge if before day 7)

Hypersensitive troponin T (µg/L)

Time frame: Baseline (Day 0)

Hypersensitive troponin T (µg/L)

Time frame: Day 2

Hypersensitive troponin T (µg/L)

Time frame: Day 4

Hypersensitive troponin T (µg/L)

Time frame: Day 7 (or day of discharge if before day 7)

Ferritin (µg/L)

Time frame: Baseline (Day 0)

Ferritin (µg/L)

Time frame: Day 2

Ferritin (µg/L)

Time frame: Day 4

Ferritin (µg/L)

Time frame: Day 7 (or day of discharge if before day 7)

CD4 cell count

CD4 refers to cluster of differentiation 4.

Time frame: Baseline (Day 0)

CD4 cell count

CD4 refers to cluster of differentiation 4.

Time frame: Day 2

CD4 cell count

CD4 refers to cluster of differentiation 4.

Time frame: Day 4

CD4 cell count

CD4 refers to cluster of differentiation 4.

Time frame: Day 7 (or day of discharge if before day 7)

CD8 cell count

CD8 refers to cluster of differentiation 8.

Time frame: Baseline (Day 0)

CD8 cell count

CD8 refers to cluster of differentiation 8.

Time frame: Day 2

CD8 cell count

CD8 refers to cluster of differentiation 8.

Time frame: Day 4

CD8 cell count

CD8 refers to cluster of differentiation 8.

Time frame: Day 7 (or day of discharge if before day 7)

Natural killer cell count

Time frame: Baseline (Day 0)

Natural killer cell count

Time frame: Day 2

Natural killer cell count

Time frame: Day 4

Natural killer cell count

Time frame: Day 7 (or day of discharge if before day 7)

Activated T cell percentage

Time frame: Baseline (Day 0)

Activated T cell percentage

Time frame: Day 2

Activated T cell percentage

Time frame: Day 4

Activated T cell percentage

Time frame: Day 7 (or day of discharge if before day 7)

Change in SARS-CoV-2 real-time polymerase chain reaction cycle threshold

Time frame: Baseline to day 7 (or day of discharge if before day 7)

Change in SARS-CoV-2 IgG serology (% of control signal = PCS)

Time frame: Baseline to day 7 (or day of discharge if before day 7)

Change in SARS-CoV-2 IgM serology (% of control signal = PCS)

Time frame: Baseline to day 7 (or day of discharge if before day 7)

Change from positivity at baseline to negativity at Day 7: yes/no for SARS-CoV-2 real time polymerase chain reaction

Time frame: Day 7 (or day of discharge if before day 7)

Change from positivity at baseline to negativity at Day 7: yes/no for SARS-CoV-2 IgG serology

Time frame: Day 7 (or day of discharge if before day 7)

Change from positivity at baseline to negativity at Day 7: yes/no for SARS-CoV-2 IgM serology

Time frame: Day 7 (or day of discharge if before day 7)

Reduction in the extent of lesions visualized on computed tomography chest scan: yes/no for grand glass opacities

A reduction in the extent of lesions is defined by a ⩾20% reduction in parenchymal involvement compared to the initial assessment

Time frame: Day 7 (or day of discharge if before day 7) +- 1 day of leeway for logistics

Reduction in the extent of lesions visualized on computed tomography chest scan: yes/no for consolidation

A reduction in the extent of lesions is defined by a ⩾20% reduction in parenchymal involvement compared to the initial assessment

Time frame: Day 7 (or day of discharge if before day 7) +- 1 day of leeway for logistics

Reduction in the extent of lesions visualized on computed tomography chest scan: yes/no for total lesions

A reduction in the extent of lesions is defined by a ⩾20% reduction in parenchymal involvement compared to the initial assessment

Time frame: Day 7 (or day of discharge if before day 7) +- 1 day of leeway for logistics

Requirement for low flow oxygen therapy during the initial hospitalisation: yes/no

Time frame: Day of hospital discharge (expected maximum of 28 days)

Requirement for high flow oxygen therapy during the initial hospitalisation: yes/no

Time frame: Day of hospital discharge (expected maximum of 28 days)

Requirement for non-invasive ventilation during the initial hospitalisation: yes/no

Time frame: Day of hospital discharge (expected maximum of 28 days)

Requirement for invasive ventilation during the initial hospitalisation: yes/no

Time frame: Day of hospital discharge (expected maximum of 28 days)

Requirement for dialysis during the initial hospitalisation: yes/no

Time frame: Day of hospital discharge (expected maximum of 28 days)

Requirement for extracorporeal membrane oxygenation during the initial hospitalisation: yes/no

Time frame: Day of hospital discharge (expected maximum of 28 days)

Classification of acute respiratory distress syndrome (ARDS) according to the Berlin criteria during initial hospitalization: absent, mild, moderate or severe

Time frame: Day of hospital discharge (expected maximum of 28 days)

Length of stay (hours) in intensive care

Time frame: Day of hospital discharge (expected maximum of 28 days)

Length of stay (hours) in hospital

Time frame: Day of hospital discharge (expected maximum of 28 days)

Days alive and without low flow oxygen therapy

Time frame: Day 28

Days alive and without high flow oxygen therapy

Time frame: Day 28

Days alive and without any oxygen therapy

Time frame: Day 28

Days alive and without non-invasive ventilation

Time frame: Day 28

Days alive and without invasive ventilation

Time frame: Day 28

Days alive and without extracorporeal membrane oxygenation

Time frame: Day 28

Days alive and without intensive care

Time frame: Day 28

Days alive and without hospitalisation

Time frame: Day 28

Mortality

Time frame: Day of hospital discharge (expected maximum of 28 days)

Mortality

Time frame: Day 28

Club cell secrectory protein polymorphism A38G

Time frame: Between day 0 and day 28

Biomarkers for Dexamethasone Response in Sars-Cov-2 / COVID-19 Pneumonia

Overview

Conditions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes