rate of inclusion and study affected by covid-19 epidemic

The aim of this study is to evaluate the possibility to repropose marketed drugs as antiviral ones, based on their ability to reverse the transcriptomic signature of the infected cells. This strategy has to be considered is the context of emerging viral diseases and of increase of resistance to antivirals. Concerning infection by Influenza viruses, the main drugs were identified and evaluated on in vitro and in vivo models: diltiazem. Therefore, it will be assess the efficacy of these the drug, compared to placebo, to treat severe flu.

Inclusion Criteria:

• patients hospitalized in intensive care units,
• patients with mechanical ventilation invasive or non-invasive or Optiflow® ventilation system.
• for a suspicion of severe flu,
• with a symptoms for less than 96 hours,
• and a respiratory failure defined by the necessity to resort to mechanical ventilation, invasive or Optiflow® Ventilation System The inclusion is conditioned to the detection of Influenza A viruses by PCR on nasopharyngeal swab.

Exclusion Criteria:

• No consent.
• Hypersensibility to Oseltamivir
• Negative PCR on nasopharyngeal swab
• Symptoms for more than 96 hours.
• Moribund patients at inclusion.
• Pregnant/nursing woman.
• Patients already taking diltiazem in the 48 hours before.
• Patients having taken more than 3 intakes of oseltamivir before randomization.
• Hemodynamic instability needing a dose of noradrenaline exceeding 2mg/h

Contraindication to diltiazem:

• sinusal dysfunction without device.
• auriculo-ventricular heart block without device.
• Cardiogenic pulmonary oedema.
• Left cardiac failure
• bradycardia<40/min
• Concomitant use of beta-blockers, antiarrythmic drugs, especially amiodarone.
• Concomitant use of ivabradine, pimozide, nifedipine, ergot alkaloids.