Efficiency of Antagonist Drugs of the Cellular Transcriptomic Signature of Influenza A Virus Infection.
- Registration Number
- NCT03212716
- Lead Sponsor
- University Hospital, Lille
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 85
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description oseltamivir + placebo Placebos oseltamivir + placebo of diltiazem diltiazem Oseltamivir oseltamivir + diltiazem diltiazem Diltiazem oseltamivir + diltiazem oseltamivir + placebo Oseltamivir oseltamivir + placebo of diltiazem
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Delay needed for the negativation of influenza A detection by RT-PCR up to 10days 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.
Length of hospitalization an average of 10 days in ICU and of 16 days in hospital 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
Trial Locations
- Locations (19)
Chu Amiens Picardie
🇫🇷Amiens, France
CH ARRAS
🇫🇷Arras, France
Ch Pierre Oudot Bourgoin Jallieu
🇫🇷Bourgoin-Jallieu, France
Hôpital Raymond Poincaré
🇫🇷Garches, France
Chru Brest
🇫🇷Brest, France
Hôpital Roger Salengro, CHRU
🇫🇷Lille, France
CH LENS
🇫🇷Lens, France
Hôpital Bretonneau
🇫🇷Tours, France
CH DOUAI
🇫🇷Douai, France
CH de Montauban
🇫🇷Montauban, France
Ch Hnfc Site de Belfort
🇫🇷Belfort, France
Ch Bethune
🇫🇷Béthune, France
Hôpital Edouard Herriot Hospices Civils de Lyon
🇫🇷Lyon, France
Ch de Valenciennes
🇫🇷Valenciennes, France
Centre Hospitalier de Versailles - Le Chesnay Rocquencourt
🇫🇷Versailles, France
Gpe Hosp Cochin Saint Vincent de Paul - Paris
🇫🇷Paris, France
Ch Regional Orleans
🇫🇷Orléans, France
Hopitaux Universitaires de Strasbourg
🇫🇷Strasbourg, France
Hu Paris Sud Site Kremlin Bicetre Aphp
🇫🇷Paris, France