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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 : Completed
First Posted : April 22, 2020
Last Update Posted : May 3, 2022
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief 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.

Condition or disease Intervention/treatment Phase
Covid 19 Hypoxemic Respiratory Failure Drug: Almitrine Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 181 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Completion Date : December 17, 2021

Arm Intervention/treatment
Experimental: Almitrine Drug: Almitrine
Intravenous almitrine at a dose of 2 µg.kg-1.min-1 during 5 days

Placebo Comparator: Placebo Drug: Placebo
Intravenous glucose 5% during 5 days

Primary Outcome Measures :
  1. Rate of endotracheal intubation [ Time Frame: 7 days ]
    Endotracheal intubation within 7 days after randomization Death will be considered as a failure (endotracheal intubation).

Secondary Outcome Measures :
  1. 28-day mortality [ Time Frame: 28 days ]
  2. In-hospital mortality [ Time Frame: 28-day ]
  3. Number of ventilator-free days [ Time Frame: 28 days ]
  4. Number of days in the ICU [ Time Frame: 28 days ]
  5. Number of days in the hospital [ Time Frame: 28 days ]
  6. 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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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04357457

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Hospital Pitié-Salpêtrière
Paris, France
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
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Principal Investigator: Yonathan FREUND, PU-PH Assistance Publique - Hôpitaux de Paris
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT04357457    
Other Study ID Numbers: APHP200461
2020-001909-22 ( EudraCT Number )
First Posted: April 22, 2020    Key Record Dates
Last Update Posted: May 3, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Yes, upon request, after approval by the primary investigator and clinical research platform of East Paris. For the purpose of IPD meta-analysis, or secondary analysis. Unidentifying data will be shared.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
COVID-19 pneumonia
Additional relevant MeSH terms:
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Respiratory Insufficiency
Respiratory Tract Infections
Pneumonia, Viral
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Respiratory System Agents