Treatment of Severe Influenza A Infection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02108366
Recruitment Status : Recruiting
First Posted : April 9, 2014
Last Update Posted : July 25, 2017
Information provided by (Responsible Party):
Dr Ivan FN Hung, The University of Hong Kong

Brief Summary:
Each year, influenza A infection caused great mortality and morbidity, especially among the elderly and individuals with chronic illness. Many of these patients are 'late presenters' who are admitted to hospital a few days after symptoms onset and have developed complications secondary to immunodysregulation. Antiviral treatment with the neuraminidase inhibitor is of limited usage for patients who presented to the hospital 48 hours after symptom onset. Apart from ventilatory and extracorporeal membrane oxygenation support, treatment options for these patients are limited. Recent animal study has demonstrated that combinations of an antiviral agent with a COX-II inhibitor can reduce mortality in mice infected with influenza virus. The investigators therefore propose to enrol patients with severe influenza A infection requiring hospitalization and oxygen support on a randomized controlled trial with celecoxib.

Condition or disease Intervention/treatment Phase
Influenza, Human Drug: Celecoxib Drug: Oseltamivir Drug: Placebo Phase 3

Detailed Description:
The aim of this double blind randomized controlled trial is to compare the clinical efficacy and safety of celecoxib combined with neuraminidase inhibitors in patients with severe influenza A infection. The hypothesis of this study is that treatment of severe influenza A infection with celecoxib will reduce mortality. The primary outcome to be assessed will be the 28-days mortality rate from hospitalization. The secondary outcomes to be assessed will be safety of the treatment, duration of intensive care, duration of ventilatory and oxygen support, the viral load and cytokine change.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Controlled Trial on the Treatment of Severe Influenza A Infection
Study Start Date : March 2014
Estimated Primary Completion Date : March 2018
Estimated Study Completion Date : June 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot
U.S. FDA Resources

Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo + oseltamivir 75mg bid for 5 days
Drug: Oseltamivir
Oseltamivir 75mg bid
Other Name: Tamiflu
Drug: Placebo
Placebo capsule identical in appearance to celecoxib capsule, containing corn starch
Other Name: Corn starch
Experimental: Celecoxib
Celecoxib 200mg daily + oseltamivir 75mg bid for 5 days
Drug: Celecoxib
Celecoxib 200mg daily
Other Name: COX II inhibitor
Drug: Oseltamivir
Oseltamivir 75mg bid
Other Name: Tamiflu

Primary Outcome Measures :
  1. Mortality rate [ Time Frame: 28 days ]
    28 days mortality from hospitalization

Secondary Outcome Measures :
  1. Viral load [ Time Frame: 7 days ]
    1 day before treatment for 1 week

  2. Cytokine [ Time Frame: 7 days ]
    1 day before treatment for 7 days

  3. Intensive care stay [ Time Frame: An expected average of 2 weeks ]
    Period under intensive care

  4. Ventilatory support period [ Time Frame: An expected average of 2 weeks ]
    Duration of patient on ventilatory support

  5. Systemic adverse events [ Time Frame: 1 week ]
    from commencement of treatment for 1 week

  6. Hospitalization [ Time Frame: An expected average of 4 weeks ]
    from hospital admission to discharge

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

Inclusion Criteria:

1) Male or female patients ≥18 years 2) Written informed consent by patient or next-of kin (if patient is too ill to consent) 3) Presumptive diagnosis of influenza A satisfying both clinical and laboratory criteria. The laboratory criteria are defined as at least one RT-PCR positive for influenza A (H1N1, H3N2, H5N1 and H7N9) from respiratory clinical specimens including nasopharyngeal samples and endotracheal aspirates. The clinical criteria are defined as hospitalization with fever or one of the symptoms suggestive of influenza infection including sore throat, rhinorrhea, cough or shortness of breath 2) Desaturation to <90% in room air by pulse oximetry and required oxygen supplement 3) Within 7 days of onset of symptoms. Patients have to fulfil all the aforementioned criteria.

Exclusion Criteria:

1) Age <18 years. 2) A known hypersensitivity to celecoxib, oseltamivir or zanamivir 3) Unable to obtain informed consents 4) Influenza A infection diagnosed beyond 7 days from symptom onset 5) Patients receiving other antiviral treatment (apart from oseltamivir or zanamivir), N-acetylcystiene, statins and tradition Chinese medicine during the current admission 6) Patients with renal impairment of creatinine clearance < 30mL/min

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 identifier (NCT number): NCT02108366

Contact: Ivan FN Hung, MD FRCP 852-22554049

Hong Kong
Ivan Hung Recruiting
Hong Kong, Hong Kong
Contact: Ivan FN Hung, MD FRCP    852 22554049   
Sub-Investigator: Kelvin To, MD FRCPath         
Sub-Investigator: KY Yuen, MD FRCPath         
Sponsors and Collaborators
The University of Hong Kong
Principal Investigator: Ivan FN HUNG, MD FRCP The University of Hong Kong

Responsible Party: Dr Ivan FN Hung, Clinical Associate Professor, The University of Hong Kong Identifier: NCT02108366     History of Changes
Other Study ID Numbers: UW 13-009
First Posted: April 9, 2014    Key Record Dates
Last Update Posted: July 25, 2017
Last Verified: July 2017

Keywords provided by Dr Ivan FN Hung, The University of Hong Kong:
influenza A

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Antiviral Agents
Anti-Infective Agents