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

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.

Study Overview

• Status: Recruiting
• Conditions: COVID-19; Corona Virus Infection; Acute Respiratory Distress Syndrome (ARDS)
• Intervention / Treatment: Drug: Lidocaine 2%; Drug: Control

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Thiên-Nga CHAMARAUX-TRAN, MD; Phone Number: 0033 3 88 12 70 81; Email: thiennga.chamaraux-tran@chru-strasbourg.fr

Study Locations

• France
  • Bas-Rhin
    • Strasbourg, Bas-Rhin, France, 67000
      • Recruiting
      • University Hospital of Hautepierre
      • Contact: Thiên-Nga CHAMARAUX-TRAN, MD; Phone Number: 0033 3 88 12 70 81; Email: thiennga.chamaraux-tran@chru-strasbourg.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lidocaine 2%; 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%; 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.
Placebo Comparator: Control; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Strasbourg, France

Publications and helpful links

General Publications

• Muller M, Lefebvre F, Harlay ML, Glady L, Becker G, Muller C, Aberkane O, Tawk M, Julians M, Romoli A, Hecketsweiler S, Schneider F, Pottecher J, Chamaraux-Tran TN. Impact of intravenous lidocaine on clinical outcomes of patients with ARDS during COVID-19 pandemia (LidoCovid): A structured summary of a study protocol for a randomised controlled trial. Trials. 2021 Feb 11;22(1):131. doi: 10.1186/s13063-021-05095-x.

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2020
• Primary Completion (Anticipated): February 1, 2024
• Study Completion (Anticipated): February 1, 2024

Study Registration Dates

• First Submitted: October 23, 2020
• First Submitted That Met QC Criteria: October 29, 2020
• First Posted (Actual): October 30, 2020

Study Record Updates

• Last Update Posted (Actual): August 18, 2022
• Last Update Submitted That Met QC Criteria: August 17, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; COVID-19; Coronavirus Infections; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lidocaine
• Other Study ID Numbers: 7820

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No