Dexmedetomidine to Improve Outcomes of ARDS in Critical Care COVID-19 Patients (COVID-DEX)

Impact of Dexmedetomidine Infusion on the Time Course and Outcomes of Acute Respiratory Distress Syndrome (ARDS) in Patients Affected by the SARS-CoV-2 (COVID-19) Admitted to Critical Care Unit

A continuous infusion of Dexmedetomidine (DEX) will be administered to 80 patients admitted to Critical Care because of signs of Respiratory Insufficiency requiring non-invasive ventilation. Measurements of respiratory performance and quantification of cellular and molecular inflammatory mediators. The primary outcome will be the avoidance of mechanical ventilation with secondary outcomes duration of mechanical ventilation, avoidance of delirium after sedation and association of mediators of inflammation to outcomes. Outcomes will be compared to a matched historical control (no DEX) series

Study Overview

• Status: Unknown
• Conditions: Inflammation; Acute Respiratory Distress Syndrome; Dexmedetomidine; Cytokine Storm; Delirium, Emergence
• Intervention / Treatment: Drug: Dexmedetomidine Injectable Product

Detailed Description

It will be an observational study, with no randomization. To evaluate the influence of Dexmedetomidine on the time course of ARDS in patients admitted to the ICU unit because of severe respiratory disease triggered by the SARS-CoV-2 (COVID-19) infection. Patients will be informed and asked to sign an Informed Consent Form.

Dexmedetomidine will be used as a sedative which is its admitted therapeutic indication in our country. Dosing will be according to its sedative properties as recommended by the manufacturer and regulation agencies. The only change is that we will study outcomes that have nothing to do with sedation but with a possible positive effect on the hyper-inflammatory state.

The study will be conducted in accordance with the "Orden SAS/3470/2009, of December 16, 2009. Government of Spain

Recruiting and Sample Size calculation We chose mortality as an endpoint to calculate sample size although our primary outcome is to minimize the requirements of mechanical ventilation. Mortality of patients admitted to the ICU because of SARS-CoV-2 (COVID-19) induced ARDS is 48%. Assuming a p value<0.05 and a power of 80%, to demonstrate a 10% decrease in mortality due to the effects of Dexmedetomidine 156 patients should be studied so there will two groups of 80 patients (cases vs historical controls).

However, due to the specific characteristics and the unknown duration of the pandemic, these numbers might not be definitive

Inclusion and Exclusion Criteria (see section)

Drug administrations Dexmedetomidine continuous intravenous infusion will be administered at 0.15 mcg/kg/h as a start and titrating according to sedative responses up to 1.5 mcg/kg/h (max admitted infusion rate)

Other sedatives (usually propofol and remifentanil) may be administered as per ICU protocol

Monitoring

• Ventilation parameters
• Invasive /non-invasive monitoring according to protocols
• The parasympathetic component of HRV will be estimated online by means of the Anesthesia Nociception Index (ANI, MDoloris Medical Systems, Lille, France).

Patient Management Patient management will be performed according to the clinical protocols of the Critical Care Units of Hospital CLINIC de Barcelona regarding the management of patients admitted to ICU because of the consequences of SARS-CoV-2 virus infection

Data Collection Demographic data including age, weight, gender, height, medical conditions, ICU severity score, SOFA score, medications, hemodynamic support, O2 fraction.

Besides regular protocolized monitoring measures for the purposes of the study it will be required:

• Routine Acid-Base equilibrium
• Routine hemogram
• Daily Citokine levels IL1b, IL6, TNFa, IL8, IL4, IL10
• Monocyte profiling Patient data will be kept anonymous except for the IP.

Outcomes to be measured are reported in their respective section

Data Analysis Analysis of the data collected includes the comparison of "primary and secondary outcomes data" acquired to a matched "historical control" with the same severity of ARDS from another COVID-19 + ICU patient with no administration of Dexmedetomidine. A "p" value less than 0.05 will be considered significant in the comparisons with the values of the "historical cohort".

Parametric or non-parametric statistical tests will be used to compare data from the control and study groups, depending on the distribution of such data.

Analysis of the time course of the mediators of inflammation sampled in the first 25 patients will be studied as changes from baseline. Mathematical models of the probability of each one or many of them to be associated with the outcomes of the study will be generated if possible

• Study Type: Observational
• Enrollment (Anticipated): 80

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

This is an observational study, with no randomization, to evaluate the influence of Dexmedetomidine on the time course of ARDS in patients admitted to the ICU unit because of severe respiratory disease triggered by the SARS-CoV-2 (COVID-19) infection.

Description

Inclusion Criteria:

• Patients with respiratory insufficiency criteria candidates to non-invasive ventilation techniques (high flow oxygen masks, non-invasive mechanical ventilation)
• SpO2 (at FiO2: 0.21) ≤ 93% equivalent to SaO2/FiO2≤442
• PaO2/ FiO2 < 300
• Bilateral opacities consistent with pulmonary edema must be present and may be detected on CT or chest radiograph that must not be fully explained by cardiac failure or fluid overload, in the physician's best estimation using available information

Exclusion Criteria:

• Affected by autoimmune disease
• Under specific therapy with Monoclonal Antibodies targeting inflammatory mediators

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
DEXMEDETOMIDINE; Patients receiving dexmedetomidine continuous infusion since their admittance to ICU. Continuous checking of the primary and secondary outcomes	Drug: Dexmedetomidine Injectable Product; continuous intravenous infusion of dexmedetomidine; Other Names: DEX IV Sedation
No-DEXMEDETOMIDINE; Historical Control patients matched for ICU admittance diagnosis, age, and concomitant disease and medication state. No Dexmedetomidine. CONtinuous checking of primary outcomes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mechanical ventilation	(Presence/Absence) requirement of mechanical ventilation	expected within first three days (non conclusive due to lack of evidence yet)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of mechanical ventilation	Duration of mechanical ventilation if it is required (hours from the start)	expected within first seven days (non conclusive due to lack of evidence yet)
Delirium on recovery from sedation	Delirium criteria as defined in DSM-4	First 24 hours after retiring dexmedetomidine sedation

Collaborators and Investigators

• Sponsor: Hospital Clinic of Barcelona

Study record dates

Study Major Dates

• Study Start (Anticipated): April 15, 2020
• Primary Completion (Anticipated): May 30, 2020
• Study Completion (Anticipated): June 30, 2020

Study Registration Dates

• First Submitted: April 15, 2020
• First Submitted That Met QC Criteria: April 22, 2020
• First Posted (Actual): April 24, 2020

Study Record Updates

• Last Update Posted (Actual): April 24, 2020
• Last Update Submitted That Met QC Criteria: April 22, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Systemic Inflammatory Response Syndrome; Postoperative Complications; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Disease; Infant, Newborn, Diseases; Shock; Lung Injury; Infant, Premature, Diseases; Delirium; Syndrome; Inflammation; Emergence Delirium; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Cytokine Release Syndrome; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: SPEC-M; SPEC-M COVID-19 (Other Identifier: Internal)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: We will share with interested researchers under the acceptance of our Ethics Committee

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No