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Completed

NCT Number: NCT04357457

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

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.

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Key information

Conditions

COVID 19 COVID-19 Coronaviridae Infections Coronavirus Infections Hypoxemic Respiratory Failure Infections Lung Diseases Nidovirales Infections Pneumonia Pneumonia, Viral RNA Virus Infections Respiration Disorders Respiratory Insufficiency Respiratory Tract Diseases Respiratory Tract Infections Virus Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Hospital Pitié-Salpêtrière

Paris, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Almitrine

Drug

Intravenous almitrine at a dose of 2 µg.kg-1.min-1 during 5 days

Placebo

Drug

Intravenous glucose 5% during 5 days

Primary outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Official study 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

Acronym: AIRVM-COVID

Important dates

Study start
2020
Primary completion
2021
Study completion
2021
First posted
Apr 22, 2020
Registry last updated
May 3, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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