Covid 19Phase 3AIRVM-COVIDNCT04357457
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 Phase 3 study testing Almitrine in people with Covid 19 and Hypoxemic Respiratory Failure, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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%. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Covid 19, Hypoxemic Respiratory Failure
- What is being tested?
- Almitrine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 181 participants
- Where
- 1 siteFrance
- Study dates
- 3 Sep 2020to 17 Dec 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
- Conditions
- Covid 19, Hypoxemic Respiratory Failure
- Being tested
- Almitrine, Placebo
- Keywords
- Almitrine, HYPOXEMIC ACUTE RESPIRATORY FAILURE, COVID-19, COVID-19 pneumonia
- Medical subject headings
- COVID-19, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlmitrineDrug
Intravenous almitrine at a dose of 2 µg.kg-1.min-1 during 5 days
PlaceboDrug
Intravenous glucose 5% during 5 days
| Study group | Role | What they receive |
|---|---|---|
| Almitrine | Experimental | Not described Receives: Drug: Almitrine |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of endotracheal intubation
Endotracheal intubation within 7 days after randomization Death will be considered as a failure (endotracheal intubation).
Measured: 7 days
Secondary outcomes (6)
28-day mortality
Measured: 28 days
In-hospital mortality
Measured: 28-day
Number of ventilator-free days
Measured: 28 days
Number of days in the ICU
Measured: 28 days
Number of days in the hospital
Measured: 28 days
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.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2020
- Study start3 Sep 2020
- Primary completion1 Oct 2021
- Study completion17 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Covid 19Studies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 181 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yonathan FREUND, PU-PH, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04357457
- Sponsor's protocol ID
- APHP200461
- Other IDs
- 2020-001909-22
- Acronym
- AIRVM-COVID
- Status last verified
- Apr 2022
- First submitted
- 20 Apr 2020
- Last updated
- 3 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 36157895
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04357457
- Acronym / sponsor ID
- AIRVM-COVID / APHP200461
- Conditions
- Covid 19, Hypoxemic Respiratory Failure
- Keywords
- Almitrine, HYPOXEMIC ACUTE RESPIRATORY FAILURE, COVID-19, COVID-19 pneumonia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 181 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 3 Sep 2020 (actual)
- Primary completion
- 1 Oct 2021 (actual)
- Study completion
- 17 Dec 2021 (actual)
- First posted
- 22 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Almitrine | Experimental | Drug: Almitrine |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlmitrineIntravenous almitrine at a dose of 2 µg.kg-1.min-1 during 5 days | Drug | Almitrine |
| PlaceboIntravenous glucose 5% during 5 days | Drug | Placebo |
Primary outcome
Rate of endotracheal intubation
Time frame: 7 days
Endotracheal intubation within 7 days after randomization Death will be considered as a failure (endotracheal intubation).
6 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2022.
- Derived from this study: PubMed 36157895Kalfon 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.
- Individual participant dataSharing planned: Yes. 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yonathan FREUND, PU-PH principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Almitrine in people with Covid 19 and Hypoxemic Respiratory Failure, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of endotracheal intubation (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04357457, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2022.