Clinical trial NCT01546506: Confirmation of the Antiviral Effects of Midodrine Identified With a Gene Expression Signature-based Screening of Inluenza A Virus Infected Cells
Official title: Confirmation of the Antiviral Effects of Midodrine Identified With a Gene Expression Signature-based Screening of Inluenza A Virus Infected Cells
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza A Virus Infection
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2012-03-07
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Rationale:

Classical antiviral therapies target viral proteins and are consequently subject to resistance. To counteract this limitation, alternative strategies have been developed that target cellular factors. We hypothesized that such an approach could also be useful to identify broad-spectrum antivirals. The influenza A virus was used as a model for its viral diversity and because of the need to develop therapies against unpredictable viruses as recently underlined by the H1N1 pandemic. Gene-expression signature-based screening identified broadly effective influenza A antivirals. Midodrine showed great results in inhibiting viral growth and was the most suited to confirm its efficacy in vivo.

The main objective of the study is to assess the efficacy of midodrine taken at usual recommended dose (7.5mg/day) versus no treatment on viral replication kinetics of virus Influenza A.

Secondary objectives: evaluation of the number of patients with a normalized viral load 2, 3 5 and 7 days post-treatment; description of the anti-viral efficacy of midodrine defined as the delay to obtain a prolonged negativity of viral RNA; description of the tolerance of midodrine, evaluation of the clinical response to study treatment; evaluation of the dynamic of viral replication; analysis of the frequency of emergence of mutants and associated resistance.

Methods:

This is a multicenter, randomized, open-label study comparing patients aged 18 to 65 years infected by influenza A virus. Nasopharyngeal washing will be performed at day 0 (randomization), 2, 3, 5 to show the viral replication evolution.

161 patients will be randomized as follows :

* Arm 1 : Midodrine, 2.5 mg, 3 times a day
* Arm 2 : No treatment The recruitment is performed by general practitioners in the Lyon area.


Eligibility criteria: Inclusion Criteria:

* men and women aged 18 to 65 years,
* with no long-term illness,
* presenting flu-like symptoms for less than 42 hours (nasal congestion, sore throat, muscle soreness, asthenia, headache, chills/sweating, fever...),
* infection with influenza A virus confirmed with a quick diagnostic test,
* outpatient care,
* must provide signed and informed consent,
* beneficiary of a health insurance.

Exclusion Criteria:

* severe form of flu,
* pregnant women or positive pregnancy test,
* breastfeeding women,
* women of childbearing-potential with no efficient contraceptive,
* history of chronic respiratory disease : asthma or chronic obstructive pulmonary disease,
* renal failure,
* Raynaud's disease,
* history of epilepsy, confusion, hallucinations or of psychoneurotic state,
* patients with an increased cardiovascular risk (\> 20% according to the Framingham scale) or with a cardiovascular history,
* patients having a congestive heart failure, swollen legs or a posture hypotension,
* patients who received a influenza vaccine for seasons 2011-2012 or 2012-2013,
* known hypersensitivity to any component of the treatment,
* topical use of nasal decongestant (except physiological serum),
* use of steroids, immunosuppressive or antipsychotics drugs (including treatments for nausea),
* use of indirect sympathomimetics drugs (ephedrine, methylphenidate, phenylephrine, pseudoephedrine),
* use of dopaminergic ergot alkaloids (bromocriptine, cabergoline, lisuride, pergolide) or vasoconstrictor ergot alkaloids (dihydroergotamine, ergotamine, methylergométrine, methylsergide),
* known hypertension treated or not,
* history of bradycardia,
* history of urinary retention,
* severe cardiopathy,
* acute angle-closure glaucoma,
* severe obliterative vasculopathy,
* vasospasm,
* thyrotoxicosis,
* pheochromocytoma,
* history of angina pectoris,
* use of guanethidine and related, iproniazide (non selective MAOIs), alpha-blockers and digitalis drugs
* use of neuraminidase inhibitors: oseltamivir, zanamivir; and M2 proton-selective ion channel inhibitors: amantadine and rimantadine

Primary outcomes:
measure: Comparison of viral replication kinetics between the 2 arms
timeFrame: 7 days
Secondary outcomes:
measure: Percentage of patients with a normalized viral load
timeFrame: 7 days
measure: Duration and severity of flu symptoms
timeFrame: 7 days
measure: Frequency, duration and level of replication of the virus in nose samples
timeFrame: 7 days
measure: Viral resistance and decrease of sensitivity of collected strains
timeFrame: 7 days
measure: Tolerance of midodrine : incidence of adverse effects
timeFrame: 7 days
Other outcomes:
Locations:
city: Bron
country: France
facility: Cabinet Médical du Dr ALIBERT
city: Bron
country: France
facility: Cabinet Médical du Dr CURE
city: Bron
country: France
facility: Centre d'Investigation Clinique de Lyon
city: Decine Charpieu
country: France
facility: Cabinet du Dr DAHAN
city: Décine Charpieu
country: France
facility: Cabinet du Dr MADELON
city: Lyon
country: France
facility: Cabinet Médical du Dr HILLION
city: Lyon
country: France
facility: Cabient Médical du Dr PIOS
city: Lyon
country: France
facility: Cabinet du Dr ATTALI
city: Lyon
country: France
facility: Cabinet du Dr COUTY
city: Lyon
country: France
facility: Hôpital D'Instruction des Armées Desgenettes
city: Lyon
country: France
facility: Cabinet Médical du Dr FORGEOIS
city: Lyon
country: France
facility: Cabinet Médical du Dr TERRASSE
city: Lyon
country: France
facility: Cabinet du Dr THIBAUT
city: Lyon
country: France
facility: Cabinet Médical du Dr BUGEL
city: Lyon
country: France
facility: Cabinet Médical du Dr CHAPDANIEL
city: Lyon
country: France
facility: Cabinet du Dr AKIKI
city: Lyon
country: France
facility: Cabinet du Dr BOURAS
city: Lyon
country: France
facility: Cabinet du Dr GREVE
city: Lyon
country: France
facility: Cabinet du Dr MANOELIAN
city: Lyon
country: France
facility: Cabinet du Dr ROCHE
city: Lyon
country: France
facility: Cabinet du Dr AZULAY TEBOUL
city: Lyon
country: France
facility: Cabinet du Dr DRUT
city: Lyon
country: France
facility: Cabinet Médical du Dr SAINT-OLIVE
city: Meyzieu
country: France
facility: Cabinet du Dr JACQUET
city: Saint Priest
country: France
facility: Cabinet du Dr CHAMPETIER
city: Saint Priest
country: France
facility: Cbinet Médical du Dr CEZANNE-BERT
city: Saint-priest
country: France
facility: Cabinet Médical du Dr SMIT
city: Saint-Symphorien d'Ozon
country: France
facility: Cabinet Médical du Dr DUBOIS
city: St Pierre de Chandieu
country: France
facility: Cabinet du Dr FARHAT
city: Venissieux
country: France
facility: Cabinet du Dr CHAIZE
city: Venissieux
country: France
facility: Cabinet Médical du Dr MARTIN
city: Venissieux
country: France
facility: Cabinet Médical du Dr THEOULE
city: Villefontaine
country: France
facility: Cabinet Médical du Dr MOREAU
city: Villeurbanne
country: France
facility: Cabinet Médical du Dr BUFFLER
city: Villeurbanne
country: France
facility: Cabinet Médical du Dr KESSOUS
city: Villeurbanne
country: France
facility: Cabinet Médical du Dr MONLOUBOU
city: Villeurbanne
country: France
facility: Cabinet Médical du Dr PERDRIX
city: Villeurbanne
country: France
facility: Cabinet Médical du Dr PILLARS
city: Villeurbanne
country: France
facility: Cabinet Médical du Dr WEBER
Study officials:
affiliation: Laboratoire de virologie, Institut de microbiologie, Centre de Biologie et de Pathologie EST, Groupement Hospitalier Est, Hospices Civils de Lyon
name: Bruno LINA, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: