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

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ClinicalTrials.gov Identifier: NCT03212716
Recruitment Status : Recruiting
First Posted : July 11, 2017
Last Update Posted : January 30, 2018
Sponsor:
Collaborator:
Ministry of Health, France
Information provided by (Responsible Party):
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, two main drugs were identified and evaluated on in vitro and in vivo models: etilefrine and diltiazem. Therefore, it will be assess the efficacy of these two drugs, compared to placebo, to treat severe flu.

Condition or disease Intervention/treatment Phase
Flu Drug: Oseltamivir Drug: Etilefrine Drug: Diltiazem Drug: Placebos Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated 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 : December 23, 2017
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot

Arm Intervention/treatment
Experimental: etilefrine
oseltamivir + etilefrine + placebo of diltiazem
Drug: Oseltamivir
150 mg twice a day during 10 days (ANSM guidelines for severe flu).

Drug: Etilefrine
10 mg x3 per day during 10 days.

Drug: Placebos
Placebo of diltiazem or placebo of etilefrine

Experimental: diltiazem
oseltamivir + diltiazem + placebo of etilefrine
Drug: Oseltamivir
150 mg twice a day during 10 days (ANSM guidelines for severe flu).

Drug: Diltiazem
60 mgx3 per day during 10 days.

Drug: Placebos
Placebo of diltiazem or placebo of etilefrine

Placebo Comparator: oseltamivir + double placebo
oseltamivir + placebo of etilefrine and placebo of diltiazem
Drug: Oseltamivir
150 mg twice a day during 10 days (ANSM guidelines for severe flu).

Drug: Placebos
Placebo of diltiazem or placebo of etilefrine




Primary Outcome Measures :
  1. 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 Measures :
  1. Delay needed for the negativation of influenza A detection by RT-PCR [ Time Frame: up to 10days ]
  2. Overall mortality [ Time Frame: At 28 days ]
  3. Length of mechanical ventilation [ Time Frame: an average of 10 days ]
  4. Change in Oxygenation (PaO2/FiO2 Ratio) [ Time Frame: 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.

  5. Length of hospitalization [ Time Frame: an average of 10 days in ICU and of 16 days in hospital ]
  6. Length of extracorporeal membrane oxygenation (ECMO) if implemented. [ Time Frame: an average of 10 days ]
  7. Transcriptomic signature determined by the DNA microarray technology and analysed by bioinformatic tools [ Time Frame: 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • patients hospitalized in intensive care units,
  • for a suspicion of severe flu,
  • with a pneumonia for less than 96 hours,
  • and a respiratory failure defined by the necessity to resort to mechanical ventilation, invasive or not, or to deliver oxygen with a PaO2/FiO2<200 mmHg.

The inclusion is conditioned to the detection of Influenza A viruses rapid detection kit on nasopharyngeal swab.

- Written informed consent

Exclusion Criteria:

  • No consent.
  • Hypersensibility to Oseltamivir
  • Negative rapid detection kit on nasopharyngeal swab.
  • Symptoms for more than 96 hours.
  • Moribund patients at inclusion.
  • Pregnant/nursing woman.
  • Patients already taking etilefrine or diltiazem in their personal home treatment.
  • Patients having taken more than 3 intakes of oseltamivir before randomization.

Contraindication to etilefrine or diltiazem:

  • sinusal dysfunction without device.
  • auriculo-ventricular heart block without device.
  • Cardiogenic pulmonary oedema.
  • bradycardia<40/min.
  • Non treated coronary insufficiency.
  • Ventricular arrythmia.
  • Hyperthyroidism.
  • Uncontrolled Hypertension.
  • Obstructive cardiomyopathy.
  • Heart valve stenosis.
  • Pheochromocytoma.
  • Concomitant use of beta-blockers, antiarrythmic drugs, especially amiodarone.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03212716


Contacts
Contact: Julien Poissy, MD, PhD 03 20 44 44 95 ext +33 julien_poissy@hotmail.fr

Locations
France
Hôpital Raymond Poincaré Recruiting
Garches, France
Principal Investigator: Djillali Annane, MD         
Hôpital Roger Salengro, CHRU Recruiting
Lille, France
Principal Investigator: Julien Poissy, MD         
Hôpital Edouard Herriot Hospices Civils de Lyon Recruiting
Lyon, France
Principal Investigator: Thomas Rimmelé, MD         
CH de Montauban Recruiting
Montauban, France
Principal Investigator: Sylvie Vimeux, MD         
Hôpital Bretonneau Recruiting
Tours, France
Principal Investigator: Denis Garot, MD         
Sponsors and Collaborators
University Hospital, Lille
Ministry of Health, France
Investigators
Principal Investigator: Julien Poissy, MD, PhD University Hospital, Lille

Responsible Party: University Hospital, Lille
ClinicalTrials.gov Identifier: NCT03212716     History of Changes
Other Study ID Numbers: 2015_65
2016-004222-42 ( EudraCT Number )
PHRC_N -15-0442 ( Other Identifier: PHRC number )
First Posted: July 11, 2017    Key Record Dates
Last Update Posted: January 30, 2018
Last Verified: January 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Lille:
Infectiology
Biology of infectious agents
Flu
Intensive care

Additional relevant MeSH terms:
Oseltamivir
Diltiazem
Etilefrine
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Calcium Channel Blockers
Membrane Transport Modulators
Vasodilator Agents
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Cardiotonic Agents
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Vasoconstrictor Agents
Adrenergic beta-1 Receptor Agonists
Adrenergic beta-Agonists
Protective Agents