Treatment of Severe Influenza A Infection

Sponsor

The University of Hong Kong (Other)

Overall Status

Completed

CT.gov ID

NCT02108366

Collaborator

(none)

107

Enrollment

Location

Arms

Actual Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

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 Design

Study Type:

Interventional

Actual Enrollment :

107 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

Actual Study Start Date :

Mar 1, 2014

Actual Primary Completion Date :

Mar 1, 2018

Actual Study Completion Date :

Jun 1, 2018

Arms and Interventions

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

Arm

Intervention/Treatment

Placebo Comparator: Placebo

Placebo + oseltamivir 75mg bid for 5 days

Drug: Oseltamivir

Oseltamivir 75mg bid

Other Names:

Tamiflu

Drug: Placebo

Placebo capsule identical in appearance to celecoxib capsule, containing corn starch

Other Names:

Corn starch

Experimental: Celecoxib

Celecoxib 200mg daily + oseltamivir 75mg bid for 5 days

Drug: Celecoxib

Celecoxib 200mg daily

Other Names:

COX II inhibitor

Drug: Oseltamivir

Oseltamivir 75mg bid

Other Names:

Tamiflu

Outcome Measures

Primary Outcome Measures

Mortality rate [28 days]
28 days mortality from hospitalization

Secondary Outcome Measures

Viral load [7 days]
1 day before treatment for 1 week
Cytokine [7 days]
1 day before treatment for 7 days
Intensive care stay [An expected average of 2 weeks]
Period under intensive care
Ventilatory support period [An expected average of 2 weeks]
Duration of patient on ventilatory support
Systemic adverse events [1 week]
from commencement of treatment for 1 week
Hospitalization [An expected average of 4 weeks]
from hospital admission to discharge

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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:

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