Clinical trial NCT03212716: Efficiency of Antagonist Drugs of the Cellular Transcriptomic Signature of Influenza A Virus Infection.
Official title: Validation of the Efficiency of Molecules Reproposed on the Basis of Their Cellular Transcriptomic Signature, Antagonist of the Signature Determined in Infection Due to Virus Influenza A.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Flu
Keywords: Infectiology
Biology of infectious agents
Flu
Intensive care
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
First posted: 2017-07-11
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of alive patients without detection of influenza A virus by RT-PCR in nasopharyngeal swabs,
timeFrame: 7 days after the beginning of the treatment.
Secondary outcomes:
measure: Delay needed for the negativation of influenza A detection by RT-PCR
timeFrame: up to 10days
measure: Overall mortality
timeFrame: At 28 days
measure: Length of mechanical ventilation
timeFrame: an average of 10 days
measure: Change in Oxygenation (PaO2/FiO2 Ratio)
timeFrame: once day for 10 days and at 28 days
measure: Length of hospitalization
timeFrame: an average of 10 days in ICU and of 16 days in hospital
measure: Length of extracorporeal membrane oxygenation (ECMO) if implemented.
timeFrame: an average of 10 days
measure: Transcriptomic signature determined by the DNA microarray technology and analysed by bioinformatic tools
timeFrame: Four time points : at inclusion, the first day after inclusion, the fourth day after inclusion, and the seventh day after inclusion
Other outcomes:
Locations:
city: Amiens
country: France
facility: Chu Amiens Picardie
city: Arras
country: France
facility: CH ARRAS
city: Belfort
country: France
facility: Ch Hnfc Site de Belfort
city: Bourgoin-Jallieu
country: France
facility: Ch Pierre Oudot Bourgoin Jallieu
city: Brest
country: France
facility: Chru Brest
city: Béthune
country: France
facility: Ch Bethune
city: Douai
country: France
facility: CH DOUAI
city: Garches
country: France
facility: Hôpital Raymond Poincaré
city: Lens
country: France
facility: CH LENS
city: Lille
country: France
facility: Hôpital Roger Salengro, CHRU
city: Lyon
country: France
facility: Hôpital Edouard Herriot Hospices Civils de Lyon
city: Montauban
country: France
facility: CH de Montauban
city: Orléans
country: France
facility: Ch Regional Orleans
city: Paris
country: France
facility: Gpe Hosp Cochin Saint Vincent de Paul - Paris
city: Paris
country: France
facility: Hu Paris Sud Site Kremlin Bicetre Aphp
city: Strasbourg
country: France
facility: Hopitaux Universitaires de Strasbourg
city: Tours
country: France
facility: Hôpital Bretonneau
city: Valenciennes
country: France
facility: Ch de Valenciennes
city: Versailles
country: France
facility: Centre Hospitalier de Versailles - Le Chesnay Rocquencourt
Study officials:
affiliation: University Hospital, Lille
name: Julien Poissy, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: