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

Sponsor
Assistance Publique - Hôpitaux de Paris (Other)
Overall Status
Completed
CT.gov ID
NCT04357457
Collaborator
(none)
181
1
2
15.4
11.7

Study Details

Study Description

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
Phase 3

Study Design

Study Type:
Interventional
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 :
Sep 3, 2020
Actual Primary Completion Date :
Oct 1, 2021
Actual Study Completion Date :
Dec 17, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. Rate of endotracheal intubation [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 [28 days]

  2. In-hospital mortality [28-day]

  3. Number of ventilator-free days [28 days]

  4. Number of days in the ICU [28 days]

  5. Number of days in the hospital [28 days]

  6. Discontinuation rate of the treatment [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 80 Years
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Hospital Pitié-Salpêtrière Paris France

Sponsors and Collaborators

  • Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Yonathan FREUND, PU-PH, Assistance Publique - Hôpitaux de Paris

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT04357457
Other Study ID Numbers:
  • APHP200461
  • 2020-001909-22
First Posted:
Apr 22, 2020
Last Update Posted:
May 3, 2022
Last Verified:
Apr 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
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
Additional relevant MeSH terms:

Study Results

No Results Posted as of May 3, 2022