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

SARS-Cov-2 Clinical Trial

— CortiCORONA  

Official title:

Determination of Biomarkers for the Prediction of Dexamethasone Response in Sars-Cov-2 / COVID-19 Pneumonia

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04619693
• Other study ID #: RECHMPL20_0292
• Secondary ID: 2020-A0206-33PHR
• Status: Terminated
• Start date: November 18, 2020
• Est. completion date: October 6, 2021

Study information

• Verified date: December 2021
• Source: University Hospital, Montpellier
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 79
• Est. completion date: October 6, 2021
• Est. primary completion date: October 6, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Pneumonia
• Pneumonia, Viral
• SARS-Cov-2

Locations

Country	Name	City	State
France	Clinique du Parc	Montpellier
France	University Hospitals of Montpellier	Montpellier

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Montpellier

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Presence/absence of incident hyperglycemia during hospitalization		Day of hospital discharge (expected maximum of 28 days)
Other	Presence/absence of secondary infection during hospitalization		Day of hospital discharge (expected maximum of 28 days)
Other	Presence/absence of cardiovascular event (ischemic, stroke, other) during hospitalization		Day of hospital discharge (expected maximum of 28 days)
Other	Presence/absence of digestive hemorrhage during hospitalization		Day of hospital discharge (expected maximum of 28 days)
Other	Presence/absence of neuro-psychiatric event (acute delirium, depressive syndrome, decompensation of an underlying psychiatric pathology) during hospitalization		Day of hospital discharge (expected maximum of 28 days)
Other	Adverse events		Day of hospital discharge (expected maximum of 28 days)
Other	Adverse events		Day 28
Primary	Treatment failure (yes/no)	Treatment failure is defined as the need to transfer the patient to intensive care for mechanical ventilation.	Hospital discharge (expected maximum of 28 days)
Secondary	Human Plasma BAK-125 proteomics profile	PeptiQuantTM Plus, Human Plasma BAK 125, Cambridge Isotope Laboratories, Inc	Baseline (day 0)
Secondary	Human Plasma BAK-125 proteomics profile	PeptiQuantTM Plus, Human Plasma BAK 125, Cambridge Isotope Laboratories, Inc	Day 7
Secondary	Circulating blood interferon level		Baseline (day 0)
Secondary	Circulating blood interferon level		Day 7
Secondary	A vector of repeated measures of SpO2	Measured at least twice per day throughout the initial hospitalization period.	Throughout initial hospitalization (expected maximum of 28 days)
Secondary	A vector of repeated measures of FiO2	Measured at least twice per day throughout the initial hospitalization period.	Throughout initial hospitalization (expected maximum of 28 days)
Secondary	A vector of repeated measures of temperature (°C)	Measured at least twice per day throughout the initial hospitalization period.	Throughout initial hospitalization (expected maximum of 28 days)
Secondary	A vector of repeated measures of respiratory rate (cycles per minute)	Measured at least twice per day throughout the initial hospitalization period.	Throughout initial hospitalization (expected maximum of 28 days)
Secondary	A vector of repeated measures of pulse (bpm)	Measured at least twice per day throughout the initial hospitalization period.	Throughout initial hospitalization (expected maximum of 28 days)
Secondary	A vector of repeated measures of systolic blood pressure (mmHg)	Measured at least twice per day throughout the initial hospitalization period.	Throughout initial hospitalization (expected maximum of 28 days)
Secondary	A vector of repeated measures of diastolic blood pressure (mmHg)	Measured at least twice per day throughout the initial hospitalization period.	Throughout initial hospitalization (expected maximum of 28 days)
Secondary	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.	Throughout initial hospitalization (expected maximum of 28 days)
Secondary	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.	Throughout initial hospitalization (expected maximum of 28 days)
Secondary	Hemoglobin		Baseline (day 0)
Secondary	Hemoglobin		Day 2
Secondary	Hemoglobin		Day 4
Secondary	Hemoglobin		Day 7 (or day of discharge if before day 7)
Secondary	Platelet count		Baseline (day 0)
Secondary	Platelet count		Day 2
Secondary	Platelet count		Day 4
Secondary	Platelet count		Day 7 (or day of discharge if before day 7)
Secondary	White blood cell count		Baseline (day 0)
Secondary	White blood cell count		Day 2
Secondary	White blood cell count		Day 4
Secondary	White blood cell count		Day 7 (or day of discharge if before day 7)
Secondary	Neutrophil percentage		Baseline (day 0)
Secondary	Neutrophil percentage		Day 2
Secondary	Neutrophil percentage		Day 4
Secondary	Neutrophil percentage		Day 7 (or day of discharge if before day 7)
Secondary	Eosinophil percentage		Baseline (day 0)
Secondary	Eosinophil percentage		Day 2
Secondary	Eosinophil percentage		Day 4
Secondary	Eosinophil percentage		Day 7 (or day of discharge if before day 7)
Secondary	Basophil percentage		Baseline (day 0)
Secondary	Basophil percentage		Day 2
Secondary	Basophil percentage		Day 4
Secondary	Basophil percentage		Day 7 (or day of discharge if before day 7)
Secondary	Lymphocyte percentage		Baseline (day 0)
Secondary	Lymphocyte percentage		Day 2
Secondary	Lymphocyte percentage		Day 4
Secondary	Lymphocyte percentage		Day 7 (or day of discharge if before day 7)
Secondary	Monocyte percentage		Baseline (day 0)
Secondary	Monocyte percentage		Day 2
Secondary	Monocyte percentage		Day 4
Secondary	Monocyte percentage		Day 7 (or day of discharge if before day 7)
Secondary	Prothrombin rate (%)		Baseline (day 0)
Secondary	Prothrombin rate (%)		Day 2
Secondary	Prothrombin rate (%)		Day 4
Secondary	Prothrombin rate (%)		Day 7 (or day of discharge if before day 7)
Secondary	Activated partial thromboplastin time ratio		Baseline (Day 0)
Secondary	Activated partial thromboplastin time ratio		Day 2
Secondary	Activated partial thromboplastin time ratio		Day 4
Secondary	Activated partial thromboplastin time ratio		Day 7 (or day of discharge if before day 7)
Secondary	Fibrinogen (g/L)		Baseline (Day 0)
Secondary	Fibrinogen (g/L)		Day 2
Secondary	Fibrinogen (g/L)		Day 4
Secondary	Fibrinogen (g/L)		Day 7 (or day of discharge if before day 7)
Secondary	D-Dimers (µg/mL)		Baseline (Day 0)
Secondary	D-Dimers (µg/mL)		Day 2
Secondary	D-Dimers (µg/mL)		Day 4
Secondary	D-Dimers (µg/mL)		Day 7 (or day of discharge if before day 7)
Secondary	Aspartate aminotransferase (ASAT; UI/L)		Baseline (Day 0)
Secondary	Aspartate aminotransferase (ASAT; UI/L)		Day 2
Secondary	Aspartate aminotransferase (ASAT; UI/L)		Day 4
Secondary	Aspartate aminotransferase (ASAT; UI/L)		Day 7 (or day of discharge if before day 7)
Secondary	Alanine aminotransferase (ALAT; UI/L)		Baseline (Day 0)
Secondary	Alanine aminotransferase (ALAT; UI/L)		Day 2
Secondary	Alanine aminotransferase (ALAT; UI/L)		Day 4
Secondary	Alanine aminotransferase (ALAT; UI/L)		Day 7 (or day of discharge if before day 7)
Secondary	Glucose (mmol/L)		Baseline (Day 0)
Secondary	Glucose (mmol/L)		Day 2
Secondary	Glucose (mmol/L)		Day 4
Secondary	Glucose (mmol/L)		Day 7 (or day of discharge if before day 7)
Secondary	Glycated haemoglobin (HbA1c; %)		Baseline (Day 0)
Secondary	Glycated haemoglobin (HbA1c; %)		Day 2
Secondary	Glycated haemoglobin (HbA1c; %)		Day 4
Secondary	Glycated haemoglobin (HbA1c; %)		Day 7 (or day of discharge if before day 7)
Secondary	Urea (mmol/L)		Baseline (Day 0)
Secondary	Urea (mmol/L)		Day 2
Secondary	Urea (mmol/L)		Day 4
Secondary	Urea (mmol/L)		Day 7 (or day of discharge if before day 7)
Secondary	Creatinine (µmol/L)		Baseline (Day 0)
Secondary	Creatinine (µmol/L)		Day 2
Secondary	Creatinine (µmol/L)		Day 4
Secondary	Creatinine (µmol/L)		Day 7 (or day of discharge if before day 7)
Secondary	Estimated glomerular filtration rate (eGFR, ml/min/1.73m^2)		Baseline (Day 0)
Secondary	Estimated glomerular filtration rate (eGFR, ml/min/1.73m^2)		Day 2
Secondary	Estimated glomerular filtration rate (eGFR, ml/min/1.73m^2)		Day 4
Secondary	Estimated glomerular filtration rate (eGFR, ml/min/1.73m^2)		Day 7 (or day of discharge if before day 7)
Secondary	Albumin (g/L)		Baseline (Day 0)
Secondary	Albumin (g/L)		Day 2
Secondary	Albumin (g/L)		Day 4
Secondary	Albumin (g/L)		Day 7 (or day of discharge if before day 7)
Secondary	C reactive protein (CRP, mg/L)		Baseline (Day 0)
Secondary	C reactive protein (CRP, mg/L)		Day 2
Secondary	C reactive protein (CRP, mg/L)		Day 4
Secondary	C reactive protein (CRP, mg/L)		Day 7 (or day of discharge if before day 7)
Secondary	Lactate dehydrogenase (LDH, UI/L)		Baseline (Day 0)
Secondary	Lactate dehydrogenase (LDH, UI/L)		Day 2
Secondary	Lactate dehydrogenase (LDH, UI/L)		Day 4
Secondary	Lactate dehydrogenase (LDH, UI/L)		Day 7 (or day of discharge if before day 7)
Secondary	Hypersensitive troponin T (µg/L)		Baseline (Day 0)
Secondary	Hypersensitive troponin T (µg/L)		Day 2
Secondary	Hypersensitive troponin T (µg/L)		Day 4
Secondary	Hypersensitive troponin T (µg/L)		Day 7 (or day of discharge if before day 7)
Secondary	Ferritin (µg/L)		Baseline (Day 0)
Secondary	Ferritin (µg/L)		Day 2
Secondary	Ferritin (µg/L)		Day 4
Secondary	Ferritin (µg/L)		Day 7 (or day of discharge if before day 7)
Secondary	CD4 cell count	CD4 refers to cluster of differentiation 4.	Baseline (Day 0)
Secondary	CD4 cell count	CD4 refers to cluster of differentiation 4.	Day 2
Secondary	CD4 cell count	CD4 refers to cluster of differentiation 4.	Day 4
Secondary	CD4 cell count	CD4 refers to cluster of differentiation 4.	Day 7 (or day of discharge if before day 7)
Secondary	CD8 cell count	CD8 refers to cluster of differentiation 8.	Baseline (Day 0)
Secondary	CD8 cell count	CD8 refers to cluster of differentiation 8.	Day 2
Secondary	CD8 cell count	CD8 refers to cluster of differentiation 8.	Day 4
Secondary	CD8 cell count	CD8 refers to cluster of differentiation 8.	Day 7 (or day of discharge if before day 7)
Secondary	Natural killer cell count		Baseline (Day 0)
Secondary	Natural killer cell count		Day 2
Secondary	Natural killer cell count		Day 4
Secondary	Natural killer cell count		Day 7 (or day of discharge if before day 7)
Secondary	Activated T cell percentage		Baseline (Day 0)
Secondary	Activated T cell percentage		Day 2
Secondary	Activated T cell percentage		Day 4
Secondary	Activated T cell percentage		Day 7 (or day of discharge if before day 7)
Secondary	Change in SARS-CoV-2 real-time polymerase chain reaction cycle threshold		Baseline to day 7 (or day of discharge if before day 7)
Secondary	Change in SARS-CoV-2 IgG serology (% of control signal = PCS)		Baseline to day 7 (or day of discharge if before day 7)
Secondary	Change in SARS-CoV-2 IgM serology (% of control signal = PCS)		Baseline to day 7 (or day of discharge if before day 7)
Secondary	Change from positivity at baseline to negativity at Day 7: yes/no for SARS-CoV-2 real time polymerase chain reaction		Day 7 (or day of discharge if before day 7)
Secondary	Change from positivity at baseline to negativity at Day 7: yes/no for SARS-CoV-2 IgG serology		Day 7 (or day of discharge if before day 7)
Secondary	Change from positivity at baseline to negativity at Day 7: yes/no for SARS-CoV-2 IgM serology		Day 7 (or day of discharge if before day 7)
Secondary	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	Day 7 (or day of discharge if before day 7) +- 1 day of leeway for logistics
Secondary	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	Day 7 (or day of discharge if before day 7) +- 1 day of leeway for logistics
Secondary	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	Day 7 (or day of discharge if before day 7) +- 1 day of leeway for logistics
Secondary	Requirement for low flow oxygen therapy during the initial hospitalisation: yes/no		Day of hospital discharge (expected maximum of 28 days)
Secondary	Requirement for high flow oxygen therapy during the initial hospitalisation: yes/no		Day of hospital discharge (expected maximum of 28 days)
Secondary	Requirement for non-invasive ventilation during the initial hospitalisation: yes/no		Day of hospital discharge (expected maximum of 28 days)
Secondary	Requirement for invasive ventilation during the initial hospitalisation: yes/no		Day of hospital discharge (expected maximum of 28 days)
Secondary	Requirement for dialysis during the initial hospitalisation: yes/no		Day of hospital discharge (expected maximum of 28 days)
Secondary	Requirement for extracorporeal membrane oxygenation during the initial hospitalisation: yes/no		Day of hospital discharge (expected maximum of 28 days)
Secondary	Classification of acute respiratory distress syndrome (ARDS) according to the Berlin criteria during initial hospitalization: absent, mild, moderate or severe		Day of hospital discharge (expected maximum of 28 days)
Secondary	Length of stay (hours) in intensive care		Day of hospital discharge (expected maximum of 28 days)
Secondary	Length of stay (hours) in hospital		Day of hospital discharge (expected maximum of 28 days)
Secondary	Days alive and without low flow oxygen therapy		Day 28
Secondary	Days alive and without high flow oxygen therapy		Day 28
Secondary	Days alive and without any oxygen therapy		Day 28
Secondary	Days alive and without non-invasive ventilation		Day 28
Secondary	Days alive and without invasive ventilation		Day 28
Secondary	Days alive and without extracorporeal membrane oxygenation		Day 28
Secondary	Days alive and without intensive care		Day 28
Secondary	Days alive and without hospitalisation		Day 28
Secondary	Mortality		Day of hospital discharge (expected maximum of 28 days)
Secondary	Mortality		Day 28
Secondary	Club cell secrectory protein polymorphism A38G		Between day 0 and day 28