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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)

Primary Purpose

Covid 19, Hypoxemic Respiratory Failure

Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Almitrine
Placebo
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Covid 19 focused on measuring Almitrine, HYPOXEMIC ACUTE RESPIRATORY FAILURE, COVID-19, COVID-19 pneumonia

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hospital Pitié-Salpêtrière

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Almitrine

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Rate of endotracheal intubation
Endotracheal intubation within 7 days after randomization Death will be considered as a failure (endotracheal intubation).

Secondary Outcome Measures

28-day mortality
In-hospital mortality
Number of ventilator-free days
Number of days in the ICU
Number of days in the hospital
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.

Full Information

First Posted
April 20, 2020
Last Updated
May 2, 2022
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT04357457
Brief 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
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
September 3, 2020 (Actual)
Primary Completion Date
October 1, 2021 (Actual)
Study Completion Date
December 17, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid 19, Hypoxemic Respiratory Failure
Keywords
Almitrine, HYPOXEMIC ACUTE RESPIRATORY FAILURE, COVID-19, COVID-19 pneumonia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
181 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Almitrine
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Almitrine
Intervention Description
Intravenous almitrine at a dose of 2 µg.kg-1.min-1 during 5 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Intravenous glucose 5% during 5 days
Primary Outcome Measure Information:
Title
Rate of endotracheal intubation
Description
Endotracheal intubation within 7 days after randomization Death will be considered as a failure (endotracheal intubation).
Time Frame
7 days
Secondary Outcome Measure Information:
Title
28-day mortality
Time Frame
28 days
Title
In-hospital mortality
Time Frame
28-day
Title
Number of ventilator-free days
Time Frame
28 days
Title
Number of days in the ICU
Time Frame
28 days
Title
Number of days in the hospital
Time Frame
28 days
Title
Discontinuation rate of the treatment
Description
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.
Time Frame
28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yonathan FREUND, PU-PH
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Pitié-Salpêtrière
City
Paris
Country
France

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
Citations:
PubMed Identifier
36157895
Citation
Kalfon P, Payen JF, Rousseau A, Chousterman B, Cachanado M, Tibi A, Audibert J, Depret F, Constantin JM, Weiss E, Remerand F, Freund Y, Simon T, Riou B. Effect of intravenous almitrine on intubation or mortality in patients with COVID-19 acute hypoxemic respiratory failure: A multicentre, randomised, double-blind, placebo-controlled trial. EClinicalMedicine. 2022 Oct;52:101663. doi: 10.1016/j.eclinm.2022.101663. Epub 2022 Sep 21.
Results Reference
derived

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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

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