Efficacy of Intravenous Almitrine in Reducing the Need for Mechanical Ventilation in Patients With Hypoxemic Acute Respiratory Failure Due to Covid-19-related Pneumonia

Covid 19 Clinical Trial

— AIRVM-COVID  

Official title:

Efficacy of Intravenous Almitrine in Reducing the Need for Mechanical Ventilation in Patients With Hypoxemic Acute Respiratory Failure Due to Covid-19-related Pneumonia: a Randomized Controlled Double-blind Study From the Skip-icu Consortium

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04357457
• Other study ID #: APHP200461
• Secondary ID: 2020-001909-22
• Status: Completed
• Phase: Phase 3
• Start date: September 3, 2020
• Est. completion date: December 17, 2021

Study information

• Verified date: April 2022
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The COVID-19 outbreak is associated with a surge in ICU bed requirement and substantial mortality (estimated between 0.5% and 1%). Admission in the intensive care unit (ICU) and need for mechanical ventilation is reportedly associated with an estimated hospital mortality of more than 30%. Furthermore, the surge in ICU bed requirement is a worldwide-shared issue, leading to sub-optimal ICU management.

In acute respiratory failure due to COVID-19-related pneumonia, vasoplegia with vascular enlargement inside the lung lesions and dilation of small vessels seen on chest CT scan largely account for severe hypoxemia whose physiological response is hyperventilation leading to hypocapnia. Almitrine, initially described to reduce intrapulmonary shunt by enhancement of hypoxic pulmonary vasoconstriction in combination with inhaled nitric oxide (iNO), redistributes pulmonary blood flow from shunt areas to lung units with normal ventilation/perfusion (VA/Q) ratio. Low dose of intravenous almitrine (2 µg.kg-1.min-1) alone also improves oxygenation (without combination with iNO) by selective pulmonary vasoconstriction of precapillary pulmonary arteries perfusing lung areas exposed to a hypoxic challenge with a slight increase in mean arterial pulmonary. Therefore, our hypothesis is that 5 days of low dose of almitrine therapy may improve the ventilation-perfusion (VA/Q) ratio at a relatively early stage of this specific lung disease and limit respiratory worsening and subsequent need for mechanical ventilation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 181
• Est. completion date: December 17, 2021
• Est. primary completion date: October 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Adults patients aged 80 years or less

• COVID-19 diagnosis defined as either positive RT-PCR for SARS-CoV-2 or COVID-19 compatible or typical chest CT pattern or positive serology for COVID-19 antibodies

• Hypoxemic acute respiratory failure with the following criteria: oxygen saturation level of 92% or less, as measured by pulsed oximetry (SpO2) under oxygen therapy with an oxygen rate of 6L/min or more.

• Hospital admission for COVID-19 within 14 days

• Patients affiliated

Exclusion Criteria:

• Hypersensitivity to the active substance or to any of the excipients

• Pregnancy or breastfeeding woman

• Known Hepatic failure (PT <50%, Factor V < 50%)

• Last known Plasma total bilirubin > 21 µmol/L

• Lactate level > 4 mmol/L

• ALT and AST levels greater than 3 times the upper limit

• Pulmonary hypertension (PAPs =37 mmHG and/or VmaxIT = 2,9 m/s) or right ventricular dysfunction

• History of pulmonary embolism

• Diagnosis of pulmonary embolism during the current hospitalization or on-going anticoagulant therapy at curative dose for thromboembolism when hospitalized

• PaCO2 > 45 mmHg

• Exacerbation of asthma or chronic respiratory failure

• Cardiogenic pulmonary oedema

• Systolic blood pressure of 90 mmHg or less, or use of vasopressors

• Urgent need for endotracheal intubation at the discretion of the treating physician

• Do-not-intubate order or estimated life expectancy less than 6 months

• Participation in another interventional research

Related Conditions & MeSH terms

• Covid 19
• COVID-19
• Hypoxemic Respiratory Failure
• Pneumonia
• Respiratory Insufficiency

Intervention

Drug:
• Almitrine
Intravenous almitrine at a dose of 2 µg.kg-1.min-1 during 5 days
• Placebo
Intravenous glucose 5% during 5 days

Locations

Country	Name	City	State
France	Hospital Pitié-Salpêtrière	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of endotracheal intubation	Endotracheal intubation within 7 days after randomization Death will be considered as a failure (endotracheal intubation).	7 days
Secondary	28-day mortality		28 days
Secondary	In-hospital mortality		28-day
Secondary	Number of ventilator-free days		28 days
Secondary	Number of days in the ICU		28 days
Secondary	Number of days in the hospital		28 days
Secondary	Discontinuation rate of the treatment	safety assessment: discontinuation rate of the treatment for arterial lactate more than 4 mmol/L, ALT/AST levels greater than 3 times the upper limit, and diagnosis of pulmonary arterial hypertension or acute cor pulmonale documented by echocardiography.	28 days