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

Primary Purpose

Flu

Status
Terminated
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Oseltamivir
Diltiazem
Placebos
Sponsored by
University Hospital, Lille
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Flu focused on measuring Infectiology, Biology of infectious agents, Flu, Intensive care

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

diltiazem

oseltamivir + placebo

Arm Description

oseltamivir + diltiazem

oseltamivir + placebo of diltiazem

Outcomes

Primary Outcome Measures

Percentage of alive patients without detection of influenza A virus by RT-PCR in nasopharyngeal swabs,

Secondary Outcome Measures

Delay needed for the negativation of influenza A detection by RT-PCR
Overall mortality
Length of mechanical ventilation
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.
Length of hospitalization
Length of extracorporeal membrane oxygenation (ECMO) if implemented.
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

Full Information

First Posted
July 4, 2017
Last Updated
February 2, 2023
Sponsor
University Hospital, Lille
Collaborators
Ministry of Health, France
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1. Study Identification

Unique Protocol Identification Number
NCT03212716
Brief Title
Efficiency of Antagonist Drugs of the Cellular Transcriptomic Signature of Influenza A Virus Infection.
Acronym
FLUNEXT
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

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Terminated
Why Stopped
rate of inclusion and study affected by covid-19 epidemic
Study Start Date
December 23, 2017 (Actual)
Primary Completion Date
May 4, 2022 (Actual)
Study Completion Date
May 4, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Lille
Collaborators
Ministry of Health, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Flu
Keywords
Infectiology, Biology of infectious agents, Flu, Intensive care

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Care ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
85 (Actual)

8. Arms, Groups, and Interventions

Arm Title
diltiazem
Arm Type
Experimental
Arm Description
oseltamivir + diltiazem
Arm Title
oseltamivir + placebo
Arm Type
Placebo Comparator
Arm Description
oseltamivir + placebo of diltiazem
Intervention Type
Drug
Intervention Name(s)
Oseltamivir
Intervention Description
150 mg twice a day during 10 days (ANSM guidelines for severe flu).
Intervention Type
Drug
Intervention Name(s)
Diltiazem
Intervention Description
60 mgx3 per day during 10 days.
Intervention Type
Drug
Intervention Name(s)
Placebos
Intervention Description
Placebo of diltiazem
Primary Outcome Measure Information:
Title
Percentage of alive patients without detection of influenza A virus by RT-PCR in nasopharyngeal swabs,
Time Frame
7 days after the beginning of the treatment.
Secondary Outcome Measure Information:
Title
Delay needed for the negativation of influenza A detection by RT-PCR
Time Frame
up to 10days
Title
Overall mortality
Time Frame
At 28 days
Title
Length of mechanical ventilation
Time Frame
an average of 10 days
Title
Change in Oxygenation (PaO2/FiO2 Ratio)
Description
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.
Time Frame
once day for 10 days and at 28 days
Title
Length of hospitalization
Time Frame
an average of 10 days in ICU and of 16 days in hospital
Title
Length of extracorporeal membrane oxygenation (ECMO) if implemented.
Time Frame
an average of 10 days
Title
Transcriptomic signature determined by the DNA microarray technology and analysed by bioinformatic tools
Description
evaluation of the capacity of tested molecules to reverse the transcriptomic signature linked to the viral infection
Time Frame
Four time points : at inclusion, the first day after inclusion, the fourth day after inclusion, and the seventh day after inclusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julien Poissy, MD, PhD
Organizational Affiliation
University Hospital, Lille
Official's Role
Principal Investigator
Facility Information:
Facility Name
Chu Amiens Picardie
City
Amiens
Country
France
Facility Name
CH ARRAS
City
Arras
Country
France
Facility Name
Ch Hnfc Site de Belfort
City
Belfort
Country
France
Facility Name
Ch Pierre Oudot Bourgoin Jallieu
City
Bourgoin-Jallieu
Country
France
Facility Name
Chru Brest
City
Brest
Country
France
Facility Name
Ch Bethune
City
Béthune
Country
France
Facility Name
CH DOUAI
City
Douai
Country
France
Facility Name
Hôpital Raymond Poincaré
City
Garches
Country
France
Facility Name
CH LENS
City
Lens
Country
France
Facility Name
Hôpital Roger Salengro, CHRU
City
Lille
Country
France
Facility Name
Hôpital Edouard Herriot Hospices Civils de Lyon
City
Lyon
Country
France
Facility Name
CH de Montauban
City
Montauban
Country
France
Facility Name
Ch Regional Orleans
City
Orléans
Country
France
Facility Name
Gpe Hosp Cochin Saint Vincent de Paul - Paris
City
Paris
Country
France
Facility Name
Hu Paris Sud Site Kremlin Bicetre Aphp
City
Paris
Country
France
Facility Name
Hopitaux Universitaires de Strasbourg
City
Strasbourg
Country
France
Facility Name
Hôpital Bretonneau
City
Tours
Country
France
Facility Name
Ch de Valenciennes
City
Valenciennes
Country
France
Facility Name
Centre Hospitalier de Versailles - Le Chesnay Rocquencourt
City
Versailles
Country
France

12. IPD Sharing Statement

Learn more about this trial

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

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