Impact of Intravenous Lidocaine on Clinical Outcomes of Patients With ARDS During COVID-19 Pandemia

Study Overview
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Brief Summary
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The purpose of our prospective monocentric, randomized, controlled trial is to evaluate the effects of intravenous lidocaine on gas exchange and inflammation in acute respiratory distress syndrome (ARDS) due or not to Covid-19 pneumonia. Half of the patients will receive intravenous lidocaine and the other half will receive intravenous NaCl 0,9 % as placebo.

Official Title
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Impact of Intravenous Lidocaine on Clinical Outcomes of Patients With ARDS During COVID-19 Pandemia

Conditions
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Acute Respiratory Distress Syndrome (ARDS), COVID-19, Corona Virus Infection

Intervention / Treatment
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* Drug: Lidocaine 2%
* Drug: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Hospitalized in ICU Presence of all of the following conditions, within one week of a clinical insult or new or worsening respiratory symptoms: PaO2/FiO2 <300 mmHg with positive end-expiratory pressure (PEEP) ≥5 cmH2O Bilateral opacities not fully explained by cardiac failure or fluid overload Intubated and sedated for mechanical protective ventilation Affiliation to the French Sociale security Beta HCG negative for women For Covid-19 subgroup: - Covid-19 infection (RT-PCR < 7 days and/or another approved diagnostic technique and/or typical CT appearance of COVID-19 pneumonia Exclusion Criteria: Allergy to amide local anesthetics Acute porphyria Disorders of atrioventricular conduction requiring a non-done permanent electrosystolic pacing Uncontrolled epilepsy Fluvoxamine treatment Class III antiarrythmic agent treatments (amiodarone, dronedarone) Class I antiarythmic agent (quinidine, disopyramide, hydroquinidine, flecainid, propafenone) Hepatocellular insufficiency defined by PT<15% in the absence of anti-vitamin K Patient under a tutelage measure or placed under judicial protection Known pregnancy Breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lidocaine 2%<br>The lidocaine infusion protocol is a bolus of 1 mg/kg (ideal weight), followed by 3mg/kg/h for the first hour, 1.5 mg/kg/h for the second hour, 0.72 mg/kg/h for the next 22 hours,and then 0.6mg/kg/h for 14 days or until extubation. | Drug: Lidocaine 2%<br>* the lidocaine infusion protocol is a bolus of 1 mg/kg (ideal weight), followed by 3mg/kg/h for the first hour, 1.5 mg/kg/h for the second hour, 0.72 mg/kg/h for the next 22 hours, and then 0.6mg/kg/h for 14 days or until extubation.<br>|
| Placebo Comparator: Control<br>The NaCl 0,9% infusion protocol is a bolus of 0.05 ml/kg (ideal weight), followed by 0.15 ml/kg/h for the first hour, 0.075 ml/kg/h for the second hour, 0.36 ml/kg/h for the next 22 hours, and then 0.03 ml/kg/h for 14 days or until extubation. | Drug: Control<br>* The NaCl 0,9% infusion protocol is a bolus of 0.05 ml/kg (ideal weight), followed by 0.15 ml/kg/h for the first hour, 0.075 ml/kg/h for the second hour, 0.36 ml/kg/h for the next 22 hours, and then 0.03 ml/kg/h for 14 days or until extubation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| alveolar-capillary gas exchange after two days of treatment | PaO2/FiO2 ratio | At 48 hours after the first treatment administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| alveolar-capillary gas exchange From day 0 to day 21 or until coming out of intensive care | PaO2/FiO2 ratio : a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. | From day 0 to day 21 or until coming out of intensive care | 
| Ventilator-free days | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. | At day 28 and at day 90 | 
| Measure the effects of Intravenous Lidocaine on Biomarkers : Ferritin | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. | At Day 0, day 2, day 7, day 14 and at day 21 | 
| Measure the effects of Intravenous Lidocaine on Biomarkers : bicarbonates | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. | At Day 0, day 2, day 7, day 14 and at day 21 | 
| Measure the effects of Intravenous Lidocaine on Biomarkers : CRP | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. | At Day 0, day 2, day 7, day 14 and at day 21 | 
| Measure the effects of Intravenous Lidocaine on Biomarkers : LDH | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. | At Day 0, day 2, day 7, day 14 and at day 21 | 
| Measure the effects of Intravenous Lidocaine on Biomarkers : IL-6 | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. | At Day 0, day 2, day 7, day 14 and at day 21 | 
| Measure the effects of Intravenous Lidocaine on Biomarkers : Tropo HS | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. | At Day 0, day 2, day 7, day 14 and at day 21 | 
| Measure the effects of Intravenous Lidocaine on Biomarkers : Triglycerides | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. | At Day 0, day 2, day 7, day 14 and at day 21 | 
| Measure the effects of Intravenous Lidocaine on Biomarkers : CBC with lymphocytes count | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. | At Day 0, day 2, day 7, day 14 and at day 21 | 
| Antithrombotic activity of Intravenous Lidocaine on platelets | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. | At Day 0, day 2, day 7, day 14 and at day 21 | 
| Antithrombotic activity of Intravenous Lidocaine on ACT ratio | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. | At Day 0, day 2, day 7, day 14 and at day 21 | 
| Antithrombotic activity of Intravenous Lidocaine on fibrinogen | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. | At Day 0, day 2, day 7, day 14 and at day 21 | 
| Antithrombotic activity of Intravenous Lidocaine on D-Dimers | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. | At Day 0, day 2, day 7, day 14 and at day 21 | 
| Antithrombotic activity of Intravenous Lidocaine on TEG | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. | At Day 0, day 2, day 7, day 14 and at day 21 | 
| Antithrombotic activity of Intravenous Lidocaine on thromboembolic events | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. | At Day 0, day 2, day 7, day 14 and at day 21 | 
| Plasma concentration of albumin and Lidocaine | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. | 4 hours after first administration, at day 2, day 7, day 14 and at day 21 | 
| Search for hemodynamic dysfynction: Blood pressure measurement in mmHg | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. Blood pressure in mmHg will be measured | daily from day one to day 14 | 
| Search for hemodynamic dysfynction: Cardiac frequency in beats per minute will be assessed | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. Cardiac frequency in beats per minute will be assessed | daily from day one to day 14 | 
| Search for hemodynamic dysfynction: Sinus rythm will be assessed | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. Sinus rythm will be assessed | daily from day one to day 14 | 
| Search for hemodynamic dysfynction: Vasopressors and inotropes drugs use will be reported | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. Vasopressors and inotropes drugs use will be reported | daily from day one to day 14 | 
| Search for hemodynamic dysfynction: EKG : PR, QRS, QTc intervals in ms will be measured | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. EKG : PR, QRS, QTc intervals in ms will be measured | daily from day one to day 14 | 
| ICU ileus: laxation response | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. | daily from Day 0 to Day 28 | 
| Opioids, sedative and curare sparing effect (drugs dosage) | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. | daily from Day 0 to Day 28 | 
| Evaluate the impact of Lidocaine IV on ICU outcomes : re-intubation | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. | From Day0 to Day28 and at Day90 | 
| Evaluate the impact of Lidocaine IV on ICU outcomes : ICU length of stay | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. | From Day0 to Day28 and at Day90 | 
| Evaluate the impact of Lidocaine IV on ICU outcomes : ICU complications | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. | From Day0 to Day28 and at Day90 | 
| Cough at extubation time or in the 24 hours after extubation or weaning from respiratory support (in case of tracheostomy) | a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. | extubation day |