Treatment of Severe Influenza A Infection

A Randomized Controlled Trial on the Treatment of Severe Influenza A Infection

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.

Study Overview

• Status: Completed
• Conditions: Influenza, Human
• Intervention / Treatment: Drug: Oseltamivir; Drug: Placebo; Drug: Celecoxib

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
• Enrollment (Actual): 107
• Phase: Phase 3

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Ivan Hung

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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: Oseltamivir; Oseltamivir 75mg bid; Other Names: Tamiflu; Drug: Celecoxib; Celecoxib 200mg daily; Other Names: COX II inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality rate	28 days mortality from hospitalization	28 days

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: The University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2014
• Primary Completion (Actual): March 1, 2018
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: March 31, 2014
• First Submitted That Met QC Criteria: April 6, 2014
• First Posted (Estimate): April 9, 2014

Study Record Updates

• Last Update Posted (Actual): October 21, 2019
• Last Update Submitted That Met QC Criteria: October 18, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: severe; celecoxib; influenza A
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Celecoxib; Oseltamivir
• Other Study ID Numbers: UW 13-009