Clinical trial NCT04619693: Biomarkers for Dexamethasone Response in Sars-Cov-2 / COVID-19 Pneumonia
Official title: Determination of Biomarkers for the Prediction of Dexamethasone Response in Sars-Cov-2 / COVID-19 Pneumonia
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Pneumonia, Viral
SARS-Cov-2
Keywords: hypoxemic pneumonia
corticosteroid
glucocorticosteroid
systemic corticosteroid
COVID-19
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
First posted: 2020-11-06
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study population corresponds to patients hospitalized for proven SARS-COV-2 pneumonia with an indication (hypoxemia) for dexamethasone

Brief summary: 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.

Detailed description: 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 criteria: 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

Primary outcomes:
measure: Treatment failure (yes/no)
timeFrame: Hospital discharge (expected maximum of 28 days)
Secondary outcomes:
measure: Human Plasma BAK-125 proteomics profile
timeFrame: Baseline (day 0)
measure: Human Plasma BAK-125 proteomics profile
timeFrame: Day 7
measure: Circulating blood interferon level
timeFrame: Baseline (day 0)
measure: Circulating blood interferon level
timeFrame: Day 7
measure: A vector of repeated measures of SpO2
timeFrame: Throughout initial hospitalization (expected maximum of 28 days)
measure: A vector of repeated measures of FiO2
timeFrame: Throughout initial hospitalization (expected maximum of 28 days)
measure: A vector of repeated measures of temperature (°C)
timeFrame: Throughout initial hospitalization (expected maximum of 28 days)
measure: A vector of repeated measures of respiratory rate (cycles per minute)
timeFrame: Throughout initial hospitalization (expected maximum of 28 days)
measure: A vector of repeated measures of pulse (bpm)
timeFrame: Throughout initial hospitalization (expected maximum of 28 days)
measure: A vector of repeated measures of systolic blood pressure (mmHg)
timeFrame: Throughout initial hospitalization (expected maximum of 28 days)
measure: A vector of repeated measures of diastolic blood pressure (mmHg)
timeFrame: Throughout initial hospitalization (expected maximum of 28 days)
measure: A vector of repeated measures of capillary glycemia (g/L)
timeFrame: Throughout initial hospitalization (expected maximum of 28 days)
measure: A vector of repeated measures of the qSOFA score
timeFrame: Throughout initial hospitalization (expected maximum of 28 days)
measure: Hemoglobin
timeFrame: Baseline (day 0)
measure: Hemoglobin
timeFrame: Day 2
measure: Hemoglobin
timeFrame: Day 4
measure: Hemoglobin
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Platelet count
timeFrame: Baseline (day 0)
measure: Platelet count
timeFrame: Day 2
measure: Platelet count
timeFrame: Day 4
measure: Platelet count
timeFrame: Day 7 (or day of discharge if before day 7)
measure: White blood cell count
timeFrame: Baseline (day 0)
measure: White blood cell count
timeFrame: Day 2
measure: White blood cell count
timeFrame: Day 4
measure: White blood cell count
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Neutrophil percentage
timeFrame: Baseline (day 0)
measure: Neutrophil percentage
timeFrame: Day 2
measure: Neutrophil percentage
timeFrame: Day 4
measure: Neutrophil percentage
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Eosinophil percentage
timeFrame: Baseline (day 0)
measure: Eosinophil percentage
timeFrame: Day 2
measure: Eosinophil percentage
timeFrame: Day 4
measure: Eosinophil percentage
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Basophil percentage
timeFrame: Baseline (day 0)
measure: Basophil percentage
timeFrame: Day 2
measure: Basophil percentage
timeFrame: Day 4
measure: Basophil percentage
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Lymphocyte percentage
timeFrame: Baseline (day 0)
measure: Lymphocyte percentage
timeFrame: Day 2
measure: Lymphocyte percentage
timeFrame: Day 4
measure: Lymphocyte percentage
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Monocyte percentage
timeFrame: Baseline (day 0)
measure: Monocyte percentage
timeFrame: Day 2
measure: Monocyte percentage
timeFrame: Day 4
measure: Monocyte percentage
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Prothrombin rate (%)
timeFrame: Baseline (day 0)
measure: Prothrombin rate (%)
timeFrame: Day 2
measure: Prothrombin rate (%)
timeFrame: Day 4
measure: Prothrombin rate (%)
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Activated partial thromboplastin time ratio
timeFrame: Baseline (Day 0)
measure: Activated partial thromboplastin time ratio
timeFrame: Day 2
measure: Activated partial thromboplastin time ratio
timeFrame: Day 4
measure: Activated partial thromboplastin time ratio
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Fibrinogen (g/L)
timeFrame: Baseline (Day 0)
measure: Fibrinogen (g/L)
timeFrame: Day 2
measure: Fibrinogen (g/L)
timeFrame: Day 4
measure: Fibrinogen (g/L)
timeFrame: Day 7 (or day of discharge if before day 7)
measure: D-Dimers (μg/mL)
timeFrame: Baseline (Day 0)
measure: D-Dimers (μg/mL)
timeFrame: Day 2
measure: D-Dimers (μg/mL)
timeFrame: Day 4
measure: D-Dimers (μg/mL)
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Aspartate aminotransferase (ASAT; UI/L)
timeFrame: Baseline (Day 0)
measure: Aspartate aminotransferase (ASAT; UI/L)
timeFrame: Day 2
measure: Aspartate aminotransferase (ASAT; UI/L)
timeFrame: Day 4
measure: Aspartate aminotransferase (ASAT; UI/L)
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Alanine aminotransferase (ALAT; UI/L)
timeFrame: Baseline (Day 0)
measure: Alanine aminotransferase (ALAT; UI/L)
timeFrame: Day 2
measure: Alanine aminotransferase (ALAT; UI/L)
timeFrame: Day 4
measure: Alanine aminotransferase (ALAT; UI/L)
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Glucose (mmol/L)
timeFrame: Baseline (Day 0)
measure: Glucose (mmol/L)
timeFrame: Day 2
measure: Glucose (mmol/L)
timeFrame: Day 4
measure: Glucose (mmol/L)
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Glycated haemoglobin (HbA1c; %)
timeFrame: Baseline (Day 0)
measure: Glycated haemoglobin (HbA1c; %)
timeFrame: Day 2
measure: Glycated haemoglobin (HbA1c; %)
timeFrame: Day 4
measure: Glycated haemoglobin (HbA1c; %)
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Urea (mmol/L)
timeFrame: Baseline (Day 0)
measure: Urea (mmol/L)
timeFrame: Day 2
measure: Urea (mmol/L)
timeFrame: Day 4
measure: Urea (mmol/L)
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Creatinine (µmol/L)
timeFrame: Baseline (Day 0)
measure: Creatinine (µmol/L)
timeFrame: Day 2
measure: Creatinine (µmol/L)
timeFrame: Day 4
measure: Creatinine (µmol/L)
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Estimated glomerular filtration rate (eGFR, ml/min/1.73m^2)
timeFrame: Baseline (Day 0)
measure: Estimated glomerular filtration rate (eGFR, ml/min/1.73m^2)
timeFrame: Day 2
measure: Estimated glomerular filtration rate (eGFR, ml/min/1.73m^2)
timeFrame: Day 4
measure: Estimated glomerular filtration rate (eGFR, ml/min/1.73m^2)
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Albumin (g/L)
timeFrame: Baseline (Day 0)
measure: Albumin (g/L)
timeFrame: Day 2
measure: Albumin (g/L)
timeFrame: Day 4
measure: Albumin (g/L)
timeFrame: Day 7 (or day of discharge if before day 7)
measure: C reactive protein (CRP, mg/L)
timeFrame: Baseline (Day 0)
measure: C reactive protein (CRP, mg/L)
timeFrame: Day 2
measure: C reactive protein (CRP, mg/L)
timeFrame: Day 4
measure: C reactive protein (CRP, mg/L)
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Lactate dehydrogenase (LDH, UI/L)
timeFrame: Baseline (Day 0)
measure: Lactate dehydrogenase (LDH, UI/L)
timeFrame: Day 2
measure: Lactate dehydrogenase (LDH, UI/L)
timeFrame: Day 4
measure: Lactate dehydrogenase (LDH, UI/L)
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Hypersensitive troponin T (µg/L)
timeFrame: Baseline (Day 0)
measure: Hypersensitive troponin T (µg/L)
timeFrame: Day 2
measure: Hypersensitive troponin T (µg/L)
timeFrame: Day 4
measure: Hypersensitive troponin T (µg/L)
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Ferritin (µg/L)
timeFrame: Baseline (Day 0)
measure: Ferritin (µg/L)
timeFrame: Day 2
measure: Ferritin (µg/L)
timeFrame: Day 4
measure: Ferritin (µg/L)
timeFrame: Day 7 (or day of discharge if before day 7)
measure: CD4 cell count
timeFrame: Baseline (Day 0)
measure: CD4 cell count
timeFrame: Day 2
measure: CD4 cell count
timeFrame: Day 4
measure: CD4 cell count
timeFrame: Day 7 (or day of discharge if before day 7)
measure: CD8 cell count
timeFrame: Baseline (Day 0)
measure: CD8 cell count
timeFrame: Day 2
measure: CD8 cell count
timeFrame: Day 4
measure: CD8 cell count
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Natural killer cell count
timeFrame: Baseline (Day 0)
measure: Natural killer cell count
timeFrame: Day 2
measure: Natural killer cell count
timeFrame: Day 4
measure: Natural killer cell count
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Activated T cell percentage
timeFrame: Baseline (Day 0)
measure: Activated T cell percentage
timeFrame: Day 2
measure: Activated T cell percentage
timeFrame: Day 4
measure: Activated T cell percentage
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Change in SARS-CoV-2 real-time polymerase chain reaction cycle threshold
timeFrame: Baseline to day 7 (or day of discharge if before day 7)
measure: Change in SARS-CoV-2 IgG serology (% of control signal = PCS)
timeFrame: Baseline to day 7 (or day of discharge if before day 7)
measure: Change in SARS-CoV-2 IgM serology (% of control signal = PCS)
timeFrame: Baseline to day 7 (or day of discharge if before day 7)
measure: Change from positivity at baseline to negativity at Day 7: yes/no for SARS-CoV-2 real time polymerase chain reaction
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Change from positivity at baseline to negativity at Day 7: yes/no for SARS-CoV-2 IgG serology
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Change from positivity at baseline to negativity at Day 7: yes/no for SARS-CoV-2 IgM serology
timeFrame: Day 7 (or day of discharge if before day 7)
measure: Reduction in the extent of lesions visualized on computed tomography chest scan: yes/no for grand glass opacities
timeFrame: Day 7 (or day of discharge if before day 7) +- 1 day of leeway for logistics
measure: Reduction in the extent of lesions visualized on computed tomography chest scan: yes/no for consolidation
timeFrame: Day 7 (or day of discharge if before day 7) +- 1 day of leeway for logistics
measure: Reduction in the extent of lesions visualized on computed tomography chest scan: yes/no for total lesions
timeFrame: Day 7 (or day of discharge if before day 7) +- 1 day of leeway for logistics
measure: Requirement for low flow oxygen therapy during the initial hospitalisation: yes/no
timeFrame: Day of hospital discharge (expected maximum of 28 days)
measure: Requirement for high flow oxygen therapy during the initial hospitalisation: yes/no
timeFrame: Day of hospital discharge (expected maximum of 28 days)
measure: Requirement for non-invasive ventilation during the initial hospitalisation: yes/no
timeFrame: Day of hospital discharge (expected maximum of 28 days)
measure: Requirement for invasive ventilation during the initial hospitalisation: yes/no
timeFrame: Day of hospital discharge (expected maximum of 28 days)
measure: Requirement for dialysis during the initial hospitalisation: yes/no
timeFrame: Day of hospital discharge (expected maximum of 28 days)
measure: Requirement for extracorporeal membrane oxygenation during the initial hospitalisation: yes/no
timeFrame: Day of hospital discharge (expected maximum of 28 days)
measure: Classification of acute respiratory distress syndrome (ARDS) according to the Berlin criteria during initial hospitalization: absent, mild, moderate or severe
timeFrame: Day of hospital discharge (expected maximum of 28 days)
measure: Length of stay (hours) in intensive care
timeFrame: Day of hospital discharge (expected maximum of 28 days)
measure: Length of stay (hours) in hospital
timeFrame: Day of hospital discharge (expected maximum of 28 days)
measure: Days alive and without low flow oxygen therapy
timeFrame: Day 28
measure: Days alive and without high flow oxygen therapy
timeFrame: Day 28
measure: Days alive and without any oxygen therapy
timeFrame: Day 28
measure: Days alive and without non-invasive ventilation
timeFrame: Day 28
measure: Days alive and without invasive ventilation
timeFrame: Day 28
measure: Days alive and without extracorporeal membrane oxygenation
timeFrame: Day 28
measure: Days alive and without intensive care
timeFrame: Day 28
measure: Days alive and without hospitalisation
timeFrame: Day 28
measure: Mortality
timeFrame: Day of hospital discharge (expected maximum of 28 days)
measure: Mortality
timeFrame: Day 28
measure: Club cell secrectory protein polymorphism A38G
timeFrame: Between day 0 and day 28
Other outcomes:
measure: Presence/absence of incident hyperglycemia during hospitalization
timeFrame: Day of hospital discharge (expected maximum of 28 days)
measure: Presence/absence of secondary infection during hospitalization
timeFrame: Day of hospital discharge (expected maximum of 28 days)
measure: Presence/absence of cardiovascular event (ischemic, stroke, other) during hospitalization
timeFrame: Day of hospital discharge (expected maximum of 28 days)
measure: Presence/absence of digestive hemorrhage during hospitalization
timeFrame: Day of hospital discharge (expected maximum of 28 days)
measure: Presence/absence of neuro-psychiatric event (acute delirium, depressive syndrome, decompensation of an underlying psychiatric pathology) during hospitalization
timeFrame: Day of hospital discharge (expected maximum of 28 days)
measure: Adverse events
timeFrame: Day of hospital discharge (expected maximum of 28 days)
measure: Adverse events
timeFrame: Day 28
Locations:
city: Montpellier
country: France
facility: Clinique du Parc
city: Montpellier
country: France
facility: University Hospitals of Montpellier
Study officials:
affiliation: University Hospital, Montpellier
name: Clement Boissin, MD
role: STUDY_DIRECTOR
References: