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Flufenamic Acid for Hospitalised Influenza Infection

Primary Purpose

Influenza A

Status

Unknown status

Phase

Phase 2

Locations

Hong Kong

Study Type

Interventional

Intervention

FFA, clarithromycin, oseltamivir

Oseltamivir alone

About this trial

This is an interventional treatment trial for Influenza A focused on measuring influenza, FFA, clarithromycin, mortality, hospitalisation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Recruited subjects include all adult patients ≥18 years hospitalised for virologically confirmed influenza infection.
Auditory temperature ≥38°C with at least one of the following symptoms (cough, sputum production, sore-throat, nasal discharge, myalgia, headache or fatigue) upon admission
Symptom duration ≤72 hours
Radiological changes of pulmonary infiltrate by chest radiography or computerised tomography
All subjects give written informed consent. Subjects must be available to complete the study and comply with study procedures. Willingness to allow for serum samples to be stored beyond the study period, for potential additional future testing to better characterise immune response.

Exclusion Criteria:

Inability to comprehend and to follow all required study procedures.
Allergy or severe reactions including renal or hepatic dysfunctions to clarithromycin, FFA, oseltamivir, amoxicillin-clavulanate or esomeprazole will be excluded
Patient with moderate renal impairment (creatinine clearance <30mL/min)
Prolonged QT or ventricular cardiac arrhythmias, including torsade de pointes.
Patient with a history of cholestatic jaundice and/or liver dysfunction associated with prior clarithromycin use
Patient on cisapride, pimozide, astemizole, terfenadine, ergotamine, dihyroergotamine, or statins medications which could not be stopped
Patient on colchicine with renal or hepatic impairment.
Pregnant or lactating women
Inability to comprehend and to follow all required study procedures
Have known human immunodeficiency virus infection
Received an experimental agent (vaccine, drug, biologic, device, blood product, or medication) within 1 month prior to recruitment in this study or expect to receive an experimental agent during this study. Unwilling to refuse participation in another clinical study through the end of this study.
Have a history of alcohol or drug abuse in the last 5 years. Have any condition that the investigator believes may interfere with successful completion of the study.

Sites / Locations

Ivan HungRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

FFA, clarithromycin, oseltamivir

Oseltamivir alone

Arm Description

oseltamivir 75mg + clarithromycin 500mg + FFA 200mg all twice daily for 2 days, followed by oseltamivir 75mg twice daily for 3 days

oseltamivir 75mg + two placebo capsules (identical in appearance to clarithromycin and FFA capsules respectively) twice daily for 2 days, followed by oseltamivir 75mg twice daily for 3 days

Outcomes

Primary Outcome Measures

Mortality

30-day mortality

Secondary Outcome Measures

NPA

nasopharyngeal aspirate viral load changes post treatment

PSI

Pneumonia severity index changes post treatment

Hospitalisation

Length of hospitalisation

Adverse events during treatment

Long-term mortality

90-day mortality

Full Information

NCT ID

NCT03238612

First Posted

July 27, 2017

Last Updated

October 21, 2019

Sponsor

The University of Hong Kong

1. Study Identification

Unique Protocol Identification Number

NCT03238612

Brief Title

Flufenamic Acid for Hospitalised Influenza Infection

Official Title

A Double-blind Randomised Controlled Trial on Flufenamic Acid for Hospitalised Influenza Infection

Study Type

Interventional

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Unknown status

Study Start Date

January 8, 2018 (Actual)

Primary Completion Date

July 31, 2020 (Anticipated)

Study Completion Date

October 31, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The University of Hong Kong

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

It is well recognized that respiratory viruses cause substantial disease burden every year. Among all known respiratory viruses, influenza virus is the greatest cause of disability-adjusted life years lost, excess hospitalizations, and deaths in the elderly and patients with chronic illness. These patients are frequently hospitalized for pneumonia secondary to these respiratory viral infection. Recently, macrolide antimicrobial clarithromycin and flufenamic acid (FFA) have been shown to inhibit seasonal influenza virus infection in human airway epithelial cells with additional anti-inflammatory effect. The investigators therefore plan to conduct a 3-year prospective study among adult patients hospitalized in Queen Mary Hospital for influenza with secondary pneumonia and randomized them to receive a course of oseltamivir + FFA + clarithromycin (as treatment) vs. a course of oseltamivir (current standard treatment as control). The objective of this prospective double-blind randomized controlled trial is to evaluate the efficacy of clarithromycin and FFA antiviral therapy in patients diagnosed to have pneumonia secondary to influenza infection.

Detailed Description

This double blind randomized-controlled trial will assess the clinical efficacy, mortality reduction and viral load reduction of clarithromycin and FFA in patients hospitalized for pneumonia secondary to influenza infection. The investigators plan to enroll at least 200 adult patients. Enrolled patients will be randomized into 2 groups. Group 1: oseltamivir 75mg + clarithromycin 500mg + FFA 200mg all twice daily for 2 days, followed by oseltamivir 75mg twice daily for 3 days ; Group 2: oseltamivir 75mg + two placebo capsules (identical in appearance to clarithromycin and FFA capsules respectively) twice daily for 2 days, followed by oseltamivir 75mg twice daily for 3 days. The placebo capsules will contain inactive starch. All patients will receive a 5-day course of amoxicillin-clavulanate 1g bid for empirical coverage of community acquired pneumonia and esomeprazole 20mg daily for prevention of non-steroidal anti-inflammatory drugs related gastropathy. Randomized treatment will be double blinded. Patients will be assigned to serial number by the study-coordinator. Each serial number will be linked to a computer-generated randomization list assigning the antiviral treatment regimens. The study medications will be dispensed by the hospital pharmacy and then to the patients by the medical ward nurses who will not know the treatment regimen of any subsequent patients. Enrolled patients could not differentiate the study or the placebo medication capsule which will be identical in appearance. The placebo capsules will contain inactive starch. There will be 50% chance of random assignment into one of the treatment or control arms. Clinical data, nasopharyngeal aspirate (NPA) and blood specimens will be collected daily if possible from admission till discharge, transfer to convalescent hospitals or death. All enrolled patients will be invited to the Infectious Disease outpatient clinic in Queen Mary Hospital for follow-up at 1 and 3 months after discharge. The investigators will retrieve your clinical information from the Clinical Medical System in the Queen Mary Hospital during follow-up.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Influenza A

Keywords

influenza, FFA, clarithromycin, mortality, hospitalisation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Prospective Randomised Controlled Trial

Masking

ParticipantInvestigator

Masking Description

Double-blind

Allocation

Randomized

Enrollment

200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

FFA, clarithromycin, oseltamivir

Arm Type

Experimental

Arm Description

oseltamivir 75mg + clarithromycin 500mg + FFA 200mg all twice daily for 2 days, followed by oseltamivir 75mg twice daily for 3 days

Arm Title

Oseltamivir alone

Arm Type

Placebo Comparator

Arm Description

oseltamivir 75mg + two placebo capsules (identical in appearance to clarithromycin and FFA capsules respectively) twice daily for 2 days, followed by oseltamivir 75mg twice daily for 3 days

Intervention Type

Drug

Intervention Name(s)

FFA, clarithromycin, oseltamivir

Other Intervention Name(s)

Antiviral combo

Intervention Description

2-day course of triple combination of clarithromycin 500mg, flufenamic acid 200mg and oseltamivir 75mg twice daily followed by oseltamivir 75mg twice daily for 3 days

Intervention Type

Drug

Intervention Name(s)

Oseltamivir alone

Other Intervention Name(s)

Antiviral

Intervention Description

2-day course of oseltamivir 75mg plus placebo capsules twice daily followed by oseltamivir 75mg twice daily for 3 days as control

Primary Outcome Measure Information:

Title

Mortality

Description

30-day mortality

Time Frame

30 days from commencement of treatment intervention

Secondary Outcome Measure Information:

Title

NPA

Description

nasopharyngeal aspirate viral load changes post treatment

Time Frame

5 days post treatment

Title

PSI

Description

Pneumonia severity index changes post treatment

Time Frame

5 days post treatment

Title

Hospitalisation

Description

Length of hospitalisation

Time Frame

Days of the subject hospitalised for the current admission up to 30 days

Title

Description

Adverse events during treatment

Time Frame

2 weeks from subjects received treatment intervention

Title

Long-term mortality

Description

90-day mortality

Time Frame

90 days from commencement of treatment intervention

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Recruited subjects include all adult patients ≥18 years hospitalised for virologically confirmed influenza infection. Auditory temperature ≥38°C with at least one of the following symptoms (cough, sputum production, sore-throat, nasal discharge, myalgia, headache or fatigue) upon admission Symptom duration ≤72 hours Radiological changes of pulmonary infiltrate by chest radiography or computerised tomography All subjects give written informed consent. Subjects must be available to complete the study and comply with study procedures. Willingness to allow for serum samples to be stored beyond the study period, for potential additional future testing to better characterise immune response. Exclusion Criteria: Inability to comprehend and to follow all required study procedures. Allergy or severe reactions including renal or hepatic dysfunctions to clarithromycin, FFA, oseltamivir, amoxicillin-clavulanate or esomeprazole will be excluded Patient with moderate renal impairment (creatinine clearance <30mL/min) Prolonged QT or ventricular cardiac arrhythmias, including torsade de pointes. Patient with a history of cholestatic jaundice and/or liver dysfunction associated with prior clarithromycin use Patient on cisapride, pimozide, astemizole, terfenadine, ergotamine, dihyroergotamine, or statins medications which could not be stopped Patient on colchicine with renal or hepatic impairment. Pregnant or lactating women Inability to comprehend and to follow all required study procedures Have known human immunodeficiency virus infection Received an experimental agent (vaccine, drug, biologic, device, blood product, or medication) within 1 month prior to recruitment in this study or expect to receive an experimental agent during this study. Unwilling to refuse participation in another clinical study through the end of this study. Have a history of alcohol or drug abuse in the last 5 years. Have any condition that the investigator believes may interfere with successful completion of the study.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Deborah Ho, BSc MSc

Phone

22554049

tipyin@yahoo.com.hk

First Name & Middle Initial & Last Name or Official Title & Degree

Teresa Tong, BSc

Phone

22551674

tongsma@hkucc.hku.hk

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ivan Hung, MD FRCP

Organizational Affiliation

The University of Hong Kong

Official's Role

Principal Investigator

Facility Information:

Facility Name

Ivan Hung

City

Hong Kong

Country

Hong Kong

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ivan FN Hung, MD FRCP

Phone

852 22554049

ivanfn@gmail.com

First Name & Middle Initial & Last Name & Degree

Kelvin To, MD FRCPath

First Name & Middle Initial & Last Name & Degree

KY Yuen, MD FRCPath

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

27884765

Citation

Hung IFN, To KKW, Chan JFW, Cheng VCC, Liu KSH, Tam A, Chan TC, Zhang AJ, Li P, Wong TL, Zhang R, Cheung MKS, Leung W, Lau JYN, Fok M, Chen H, Chan KH, Yuen KY. Efficacy of Clarithromycin-Naproxen-Oseltamivir Combination in the Treatment of Patients Hospitalized for Influenza A(H3N2) Infection: An Open-label Randomized, Controlled, Phase IIb/III Trial. Chest. 2017 May;151(5):1069-1080. doi: 10.1016/j.chest.2016.11.012. Epub 2016 Nov 22.

Results Reference

background

PubMed Identifier

23450336

Citation

Hung IFN, To KKW, Lee CK, Lee KL, Yan WW, Chan K, Chan WM, Ngai CW, Law KI, Chow FL, Liu R, Lai KY, Lau CCY, Liu SH, Chan KH, Lin CK, Yuen KY. Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection. Chest. 2013 Aug;144(2):464-473. doi: 10.1378/chest.12-2907.

Results Reference

background

PubMed Identifier

20061398

Citation

Li IW, Hung IF, To KK, Chan KH, Wong SS, Chan JF, Cheng VC, Tsang OT, Lai ST, Lau YL, Yuen KY. The natural viral load profile of patients with pandemic 2009 influenza A(H1N1) and the effect of oseltamivir treatment. Chest. 2010 Apr;137(4):759-68. doi: 10.1378/chest.09-3072. Epub 2010 Jan 8.

Results Reference

background

PubMed Identifier

21248066

Citation

Hung IF, To KK, Lee CK, Lee KL, Chan K, Yan WW, Liu R, Watt CL, Chan WM, Lai KY, Koo CK, Buckley T, Chow FL, Wong KK, Chan HS, Ching CK, Tang BS, Lau CC, Li IW, Liu SH, Chan KH, Lin CK, Yuen KY. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis. 2011 Feb 15;52(4):447-56. doi: 10.1093/cid/ciq106. Epub 2011 Jan 19.

Results Reference

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Flufenamic Acid for Hospitalised Influenza Infection

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