Efficiency of Antagonist Drugs of the Cellular Transcriptomic Signature of Influenza A Virus Infection.

Flu Clinical Trial

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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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03212716
• Other study ID #: 2015_65
• Secondary ID: 2016-004222-42PH
• Status: Terminated
• Phase: Phase 2
• Start date: December 23, 2017
• Est. completion date: May 4, 2022

Study information

• Verified date: January 2023
• Source: University Hospital, Lille
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 85
• Est. completion date: May 4, 2022
• Est. primary completion date: May 4, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Flu
• Infections

Intervention

Drug:
• Oseltamivir
150 mg twice a day during 10 days (ANSM guidelines for severe flu).
• Diltiazem
60 mgx3 per day during 10 days.
• Placebos
Placebo of diltiazem

Locations

Country	Name	City	State
France	Chu Amiens Picardie	Amiens
France	CH ARRAS	Arras
France	Ch Hnfc Site de Belfort	Belfort
France	Ch Bethune	Béthune
France	Ch Pierre Oudot Bourgoin Jallieu	Bourgoin-Jallieu
France	Chru Brest	Brest
France	CH DOUAI	Douai
France	Hôpital Raymond Poincaré	Garches
France	CH LENS	Lens
France	Hôpital Roger Salengro, CHRU	Lille
France	Hôpital Edouard Herriot Hospices Civils de Lyon	Lyon
France	CH de Montauban	Montauban
France	Ch Regional Orleans	Orléans
France	Gpe Hosp Cochin Saint Vincent de Paul - Paris	Paris
France	Hu Paris Sud Site Kremlin Bicetre Aphp	Paris
France	Hopitaux Universitaires de Strasbourg	Strasbourg
France	Hôpital Bretonneau	Tours
France	Ch de Valenciennes	Valenciennes
France	Centre Hospitalier de Versailles - Le Chesnay Rocquencourt	Versailles

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Lille	Ministry of Health, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Delay needed for the negativation of influenza A detection by RT-PCR		up to 10days
Secondary	Overall mortality		At 28 days
Secondary	Length of mechanical ventilation		an average of 10 days
Secondary	Change in Oxygenation (PaO2/FiO2 Ratio)	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.	once day for 10 days and at 28 days
Secondary	Length of hospitalization		an average of 10 days in ICU and of 16 days in hospital
Secondary	Length of extracorporeal membrane oxygenation (ECMO) if implemented.		an average of 10 days
Secondary	Transcriptomic signature determined by the DNA microarray technology and analysed by bioinformatic tools	evaluation of the capacity of tested molecules to reverse the transcriptomic signature linked to the viral infection	Four time points : at inclusion, the first day after inclusion, the fourth day after inclusion, and the seventh day after inclusion