Almitrine in COVID-19 Patients With ARDS Treated by HFNO

Use of Almitrine in COVID-19 Patients With Acute Respiratory Distress Syndrome Treated by High-flow Nasal Canula Oxygen Therapy

The purpose of this study is to determine the effects of Almitrine administration on oxygenation in COVID-19 patients with acute respiratory distress syndrome treated by high-flow nasal canula oxygen therapy as first-line ventilatory support.

Study Overview

• Status: Recruiting
• Conditions: ARDS; Hypoxemia
• Intervention / Treatment: Drug: Administration of Almitrine

Detailed Description

From December 2019, the emergent coronavirus SARSCoV-2 is responsible for the worldwide pandemic of coronavirus disease (COVID-19). Although SARSCoV-2 infection is mainly responsible for mild respiratory symptoms, up to 70% of hospitalized patients with COVID-19-related pneumoniae may develop severe respiratory disease, progressing to acute respiratory distress syndrome (ARDS). These patients may experience severe but well-tolerated hypoxemia, so-called "happy hypoxemia" which may be related to blunted hypoxic vasoconstriction. Almitrine is a selective pulmonary vasoconstrictor that has been reported to improve the oxygenation in ARDS patients by increasing hypoxic pulmonary vasoconstriction. Some small case series reported that the use of Almitrine in mechanically ventilated COVID-19 patients with ARDS improved oxygenation. Given the "happy hypoxemia" phenomenon, it has been suggested to use high-flow nasal canula therapy (HFNO) as first-line ventilatory support in COVID-19 patients with ARDS, since the risk of aerosolization with HFNO was similar to that with standard oxygen therapy and lower to that with non-invasive ventilation. However, the effects of Almitrine in spontaneously breathing patients with ARDS has not been reported so far. Thus, the main goal of this study is to investigate the effects of Almitrine on oxygenation of COVID-19 patients with ARDS treated by HFNO as first-line ventilatory support. The second goal of this study is to determine the effects of Almitrine on respiratory mechanics and hymodynamics.

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

• Study Contact: Name: Jean DELLAMONICA, MD, PhD; Phone Number: +33492035510; Email: dellamonica.j@chu-nice.fr
• Study Contact Backup: Name: Clément SACCHERI, MD; Phone Number: +33492035510; Email: saccheri.c@chu-nice.fr

Study Locations

• France
  • Nice, France, 06200
    • Recruiting
    • CHU de Nice
    • Contact: Clément JOZWIAK; Phone Number: +33492035510; Email: saccheri.c@chu-nice.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

• Sampling Method: Non-Probability Sample

Study Population

Eligible patients are spontaneously breathing COVID-19 patients with moderate to severe ARDS treated by high-flow nasal canula oxygen therapy as first-line ventilatory support with persitent severe hypoxemia after awake prone positioning.

Description

Inclusion Criteria:

1. Patients treated by high-flow nasal canula oxygen
2. Positive COVID-19 real-time reverse transcriptase-polymerase chain reaction assay in nasal swabs

3. Persistent severe hypoxemia after awake prone positioning defined by one or more of the following criteria:

   1. SpO2 < 96% with FiO2 > 80%
   2. PaO2/FiO2 ratio < 100 with FiO2 > 80%
4. Patients treated by Almitrine

Exclusion Criteria:

1. Age <18 years old and pregnant women
2. Patients under legal protection
3. Patients with a do not intubate or do not resuscitate decision
4. Patients requiring immediate invasive mechanical ventilation
5. Contraindication to Almitrine
6. Poor echogenicity

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Almitrine treated patients; Administration of Almitrine in spontaneoulsy breathing COVID-19 patients with moderate to severe ARDS treated by high-flow nasal canula oxygen therapy as first-line ventilatory support with persitent severe hypoxemia after awake prone positioning.	Drug: Administration of Almitrine; Administration of Almitrine (intravenous bolus of 0.5 mg/kg over 30 minutes followed by a continuous perfusion of 16 mg/kg/min in responders)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Almitrine-induced increase in Pa02/FiO2 ratio.	The PaO2/FiO2 ratio will be calculated before and after the bolus of Almitrine. Patients with increase in PaO2/FiO2 ratio > 20% will be considered as responders.	The 30-minute duration of Almitrine bolus

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients requiring intubation	To assess the proportion of patients who will require to be intubated during their ICU stay.	ICU stay
Proportion of patients exhibiting right ventricular failure and/or right ventricular dilation and/or acute core pulmonale after administration of Almitrine.	To assess the proportion of patients who will experience right ventricular failure and/or right ventricular dilation and/or acute core pulmonale after administration of Almitrine.	The 30-minute duration of Almitrine bolus
Clinical prediction of Almitrine effects	To test the ability of different respiratory variables and radiological patterns to predict the response to Almitrine in terms of oxygenation	The 30-minute duration of Almitrine bolus
Radiological prediction of Almitrine effects	To test the ability of different radiological patterns to predict the response to Almitrine in terms of oxygenation	The 30-minute duration of Almitrine bolus

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): January 31, 2022
• Study Completion (Anticipated): March 31, 2022

Study Registration Dates

• First Submitted: January 28, 2022
• First Submitted That Met QC Criteria: January 28, 2022
• First Posted (Actual): January 31, 2022

Study Record Updates

• Last Update Posted (Actual): February 25, 2022
• Last Update Submitted That Met QC Criteria: February 22, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Respiratory; Hypoxia; Respiratory System Agents; Almitrine
• Other Study ID Numbers: 22reamedcovid01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No data sharing plan is scheduled

Drug and device information, study documents

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