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

Sponsor

University Hospital, Lille (Other)

Overall Status

Recruiting

CT.gov ID

NCT03212716

Collaborator

Ministry of Health, France (Other)

300

Enrollment

Locations

Arms

71.3

Anticipated Duration (Months)

15.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Flu	Drug: Oseltamivir Drug: Diltiazem Drug: Placebos	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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.

Actual Study Start Date :

Dec 23, 2017

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: diltiazem oseltamivir + diltiazem	Drug: Oseltamivir 150 mg twice a day during 10 days (ANSM guidelines for severe flu). Drug: Diltiazem 60 mgx3 per day during 10 days.
Placebo Comparator: oseltamivir + placebo oseltamivir + placebo of diltiazem	Drug: Oseltamivir 150 mg twice a day during 10 days (ANSM guidelines for severe flu). Drug: Placebos Placebo of diltiazem

Arm

Intervention/Treatment

Experimental: diltiazem

oseltamivir + diltiazem

Drug: Oseltamivir

150 mg twice a day during 10 days (ANSM guidelines for severe flu).

Drug: Diltiazem

60 mgx3 per day during 10 days.

Placebo Comparator: oseltamivir + placebo

oseltamivir + placebo of diltiazem

Drug: Oseltamivir

150 mg twice a day during 10 days (ANSM guidelines for severe flu).

Drug: Placebos

Placebo of diltiazem

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country
1	Chu Amiens Picardie	Amiens	France
2	CH ARRAS	Arras	France
3	Ch Hnfc Site de Belfort	Belfort	France
4	Ch Pierre Oudot Bourgoin Jallieu	Bourgoin-Jallieu	France
5	Chru Brest	Brest	France
6	Ch Bethune	Béthune	France
7	CH DOUAI	Douai	France
8	Hôpital Raymond Poincaré	Garches	France
9	CH LENS	Lens	France
10	Hôpital Roger Salengro, CHRU	Lille	France
11	Hôpital Edouard Herriot Hospices Civils de Lyon	Lyon	France
12	CH de Montauban	Montauban	France
13	Ch Regional Orleans	Orléans	France
14	Gpe Hosp Cochin Saint Vincent de Paul - Paris	Paris	France
15	Hu Paris Sud Site Kremlin Bicetre Aphp	Paris	France
16	Hopitaux Universitaires de Strasbourg	Strasbourg	France
17	Hôpital Bretonneau	Tours	France
18	Ch de Valenciennes	Valenciennes	France
19	Centre Hospitalier de Versailles - Le Chesnay Rocquencourt	Versailles	France