NCT03238612

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
200

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jan 2018

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 27, 2017

Completed
7 days until next milestone

First Posted

Study publicly available on registry

August 3, 2017

Completed
5 months until next milestone

Study Start

First participant enrolled

January 8, 2018

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 31, 2020

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 31, 2020

Completed
Last Updated

October 22, 2019

Status Verified

October 1, 2019

Enrollment Period

2.6 years

First QC Date

July 27, 2017

Last Update Submit

October 21, 2019

Conditions

Keywords

influenzaFFAclarithromycinmortalityhospitalisation

Outcome Measures

Primary Outcomes (1)

  • Mortality

    30-day mortality

    30 days from commencement of treatment intervention

Secondary Outcomes (5)

  • NPA

    5 days post treatment

  • PSI

    5 days post treatment

  • Hospitalisation

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

  • AE

    2 weeks from subjects received treatment intervention

  • Long-term mortality

    90 days from commencement of treatment intervention

Study Arms (2)

FFA, clarithromycin, oseltamivir

EXPERIMENTAL

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

Drug: FFA, clarithromycin, oseltamivir

Oseltamivir alone

PLACEBO COMPARATOR

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

Drug: Oseltamivir alone

Interventions

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

Also known as: Antiviral combo
FFA, clarithromycin, oseltamivir

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

Also known as: Antiviral
Oseltamivir alone

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Ivan Hung

Hong Kong, Hong Kong

RECRUITING

Related Publications (4)

  • 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.

    PMID: 27884765BACKGROUND
  • 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.

    PMID: 23450336BACKGROUND
  • 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.

    PMID: 20061398BACKGROUND
  • 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.

    PMID: 21248066BACKGROUND

MeSH Terms

Conditions

Influenza, Human

Interventions

Fatty Acids, NonesterifiedClarithromycinOseltamivirAntiviral Agents

Condition Hierarchy (Ancestors)

Respiratory Tract InfectionsInfectionsOrthomyxoviridae InfectionsRNA Virus InfectionsVirus DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Fatty AcidsLipidsErythromycinMacrolidesPolyketidesLactonesOrganic ChemicalsAcetamidesAmidesCyclohexenesCyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsAnti-Infective AgentsTherapeutic UsesPharmacologic ActionsChemical Actions and Uses

Study Officials

  • Ivan Hung, MD FRCP

    The University of Hong Kong

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Deborah Ho, BSc MSc

CONTACT

Teresa Tong, BSc

CONTACT

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Masking Details
Double-blind
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Prospective Randomised Controlled Trial
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 27, 2017

First Posted

August 3, 2017

Study Start

January 8, 2018

Primary Completion

July 31, 2020

Study Completion

October 31, 2020

Last Updated

October 22, 2019

Record last verified: 2019-10

Locations