Flu
Conditions
Keywords
Infectiology, Biology of infectious agents, Flu, Intensive care
Brief summary
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.
Interventions
DRUGOseltamivir
150 mg twice a day during 10 days (ANSM guidelines for severe flu).
DRUGDiltiazem
60 mgx3 per day during 10 days.
DRUGPlacebos
Placebo of diltiazem
Sponsors
Ministry of Health, France
University Hospital, Lille
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of alive patients without detection of influenza A virus by RT-PCR in nasopharyngeal swabs, | 7 days after the beginning of the treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall mortality | At 28 days | — |
| Length of mechanical ventilation | an average of 10 days | — |
| Change in Oxygenation (PaO2/FiO2 Ratio) | once day for 10 days and at 28 days | Arterial blood samples for blood gas analysis are collected during the treatment period. The differences in the mean values of PaO2/FiO2 ratio are registered and analysed. |
| Delay needed for the negativation of influenza A detection by RT-PCR | up to 10days | — |
| Length of extracorporeal membrane oxygenation (ECMO) if implemented. | an average of 10 days | — |
| Transcriptomic signature determined by the DNA microarray technology and analysed by bioinformatic tools | Four time points : at inclusion, the first day after inclusion, the fourth day after inclusion, and the seventh day after inclusion | evaluation of the capacity of tested molecules to reverse the transcriptomic signature linked to the viral infection |
| Length of hospitalization | an average of 10 days in ICU and of 16 days in hospital | — |
Countries
France
Outcome results
None listed