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

Inflammation Clinical Trial

— COVID-DEX  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04358627
• Other study ID #: SPEC-M
• Secondary ID: SPEC-M COVID-19
• Status: Not yet recruiting
• Start date: April 15, 2020
• Est. completion date: June 30, 2020

Study information

• Verified date: April 2020
• Source: Hospital Clinic of Barcelona
• Contact: Pedro L Gambus, PhD MD
• Phone: +34687075332
• Email: plgambus[@]clinic.cat
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: June 30, 2020
• Est. primary completion date: May 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Cytokine Storm
• Delirium
• Delirium, Emergence
• Dexmedetomidine
• Emergence Delirium
• Inflammation
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

Drug:
• Dexmedetomidine Injectable Product
continuous intravenous infusion of dexmedetomidine

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Clinic of Barcelona

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mechanical ventilation	(Presence/Absence) requirement of mechanical ventilation	expected within first three days (non conclusive due to lack of evidence yet)
Secondary	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)
Secondary	Delirium on recovery from sedation	Delirium criteria as defined in DSM-4	First 24 hours after retiring dexmedetomidine sedation