Efficacy of Intravenous Almitrine in Reducing the Need for Mechanical Ventilation in Patients With Hypoxemic Acute Respiratory Failure Due to Covid-19-related Pneumonia (AIRVM-COVID)
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|ClinicalTrials.gov Identifier: NCT04357457|
Recruitment Status : Active, not recruiting
First Posted : April 22, 2020
Last Update Posted : October 18, 2021
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.
|Condition or disease||Intervention/treatment||Phase|
|Covid 19 Hypoxemic Respiratory Failure||Drug: Almitrine Drug: Placebo||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||181 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
|Actual Study Start Date :||September 3, 2020|
|Actual Primary Completion Date :||October 1, 2021|
|Estimated Study Completion Date :||October 2021|
Intravenous almitrine at a dose of 2 µg.kg-1.min-1 during 5 days
|Placebo Comparator: Placebo||
Intravenous glucose 5% during 5 days
- Rate of endotracheal intubation [ Time Frame: 7 days ]Endotracheal intubation within 7 days after randomization Death will be considered as a failure (endotracheal intubation).
- 28-day mortality [ Time Frame: 28 days ]
- In-hospital mortality [ Time Frame: 28-day ]
- Number of ventilator-free days [ Time Frame: 28 days ]
- Number of days in the ICU [ Time Frame: 28 days ]
- Number of days in the hospital [ Time Frame: 28 days ]
- Discontinuation rate of the treatment [ Time Frame: 28 days ]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.
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04357457
|Principal Investigator:||Yonathan FREUND, PU-PH||Assistance Publique - Hôpitaux de Paris|