Almitrine in COVID-19 Patients With ARDS Treated by HFNO

Completed

• Conditions: ARDS; Hypoxemia
• Interventions: Drug: Administration of Almitrine

• Registration Number: NCT05216575
• Lead Sponsor: Centre Hospitalier Universitaire de Nice

Brief Summary

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.

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 Timeline

• Study Start: 2021-01-01
• Study First Submitted: 2022-01-28
• Study First Submitted QC: 2022-01-28
• Primary Completion: 2022-01-31
• Study Completion: 2022-01-31
• Study First Posted: 2022-01-31
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-22
• Last Update Posted: 2025-04-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 62

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Almitrine treated patients	Administration of Almitrine	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.

Primary Outcome Measures

Name	Time	Method
Almitrine-induced increase in Pa02/FiO2 ratio.	The 30-minute duration of Almitrine bolus	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

CHU de NICE; 🇫🇷 Nice, France