E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with hypoxemic acute respiratory failure due to COVID-19-related pneumonia |
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E.1.1.1 | Medical condition in easily understood language |
Patients with hypoxemic acute respiratory failure due to COVID-19-related pneumonia |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of 5-day almitrine therapy (2 µg.kg-1.min-1) in reducing the need for mechanical invasive ventilation in patients with hypoxemic respiratory failure due to COVID-19-related pneumonia at seven days |
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E.2.2 | Secondary objectives of the trial |
To assess the efficacy of intravenous almitrine in reducing:
-in-hospital mortality
-28-day all-cause mortality
-duration of mechanical ventilation
-hospitalization rate in the ICU
-length of stay in the ICU
-hospital length of stay
To assess safety and side effects of intravenous almitrine
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Adults patients aged 75 years of less
- COVID-19 diagnosis in the past 14 days defined as either positive rt-PCR for SARS-cov2 or compatible or lesion in lung in CT (consistent or typical for covid19) or positive serology
- Hypoxemic 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 6 L/min or more.
- Hospital admission within 14 days
- Patients affiliated to French social security (“AME” excepted)
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E.4 | Principal 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%)
- Known Plasma total bilirubin > 21 µmol/L during hospitalization
- Lactate level > 4 mmol/L
- Known pulmonary hypertension or right ventricular dysfunction
- Diagnosis of pulmonary embolism during the current hospitalization or on-going anticoagulant therapy at curative dose for thromboembolism when hospitalized
- PaCO2 of >45 mmHg
- Exacerbation of asthma or chronic respiratory failure
- Cardiogenic pulmonary edema
- Systolic blood pressure of 90 mmHg or less, or use of vasopressor
- 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Endotracheal intubation within 7 days after randomization. Death will be considered as a failure (endotracheal intubation). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- 28-day mortality
- In-hospital mortality
- Number of ventilator-free days between at day 28
- Number of days in the ICU
- Number of days in the hospital
- Safety assessment: discontinuation rate of the treatment for arterial lactate more than 4 mmol/L, ALT/AST levels greater then 3 times the upper limit, and diagnosis of pulmonary arterial hypertension or acute cor pulmonale documented by echocardiography |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |