Influenza APhase 2NCT03238612
Flufenamic Acid for Hospitalised Influenza Infection
A Phase 2 study testing FFA, clarithromycin, oseltamivir and Oseltamivir alone in people with Influenza A, run by The University of Hong Kong at 1 site in Hong Kong.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Influenza A
- What is being tested?
- FFA, clarithromycin, oseltamivir and Oseltamivir alone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteHong Kong
- Study dates
- 8 Jan 2018to 31 Oct 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Hong Kong1 site, 1 recruiting
- Recruiting
Ivan Hung
Hong Kong
Ivan FN Hung, MD FRCP, 852 22554049, ivanfn@gmail.com
Kelvin To, MD FRCPath
About this study
Official title: A Double-blind Randomised Controlled Trial on Flufenamic Acid for Hospitalised Influenza Infection
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.
Read the 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.
- Conditions
- Influenza A
- Being tested
- FFA, clarithromycin, oseltamivir, Oseltamivir alone
- Keywords
- influenza, FFA, clarithromycin, mortality, hospitalisation
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FFA, clarithromycin, oseltamivirDrug
Also called Antiviral combo
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
Oseltamivir aloneDrug
Also called Antiviral
2-day course of oseltamivir 75mg plus placebo capsules twice daily followed by oseltamivir 75mg twice daily for 3 days as control
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Oseltamivir alone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality
30-day mortality
Measured: 30 days from commencement of treatment intervention
Secondary outcomes (5)
NPA
nasopharyngeal aspirate viral load changes post treatment
Measured: 5 days post treatment
PSI
Pneumonia severity index changes post treatment
Measured: 5 days post treatment
Hospitalisation
Length of hospitalisation
Measured: Days of the subject hospitalised for the current admission up to 30 days
AE
Adverse events during treatment
Measured: 2 weeks from subjects received treatment intervention
Long-term mortality
90-day mortality
Measured: 90 days from commencement of treatment intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2017
- Study start8 Jan 2018
- Primary completion31 Jul 2020 (estimated)
- Study completion31 Oct 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Influenza AStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective Randomised Controlled Trial
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ivan Hung, MD FRCP, Principal investigator, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03238612
- Sponsor's protocol ID
- UW 16-418
- Status last verified
- Oct 2019
- First submitted
- 27 Jul 2017
- Last updated
- 22 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 27884765Hung 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.
PubMed 23450336Li 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.
PubMed 20061398Hung 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.
PubMed 21248066
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind Randomised Controlled Trial on Flufenamic Acid for Hospitalised Influenza Infection
- ClinicalTrials.gov ID
- NCT03238612
- Acronym / sponsor ID
- UW 16-418
- Conditions
- Influenza A
- Keywords
- influenza, FFA, clarithromycin, mortality, hospitalisation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Study start
- 8 Jan 2018 (actual)
- Primary completion
- 31 Jul 2020 (estimated)
- Study completion
- 31 Oct 2020 (estimated)
- First posted
- 3 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Prospective Randomised Controlled Trial
| Arm | Type | Receives |
|---|---|---|
| FFA, clarithromycin, oseltamivir | Experimental | Drug: FFA, clarithromycin, oseltamiviroseltamivir 75mg + clarithromycin 500mg + FFA 200mg all twice daily for 2 days, followed by oseltamivir 75mg twice daily for 3 days |
| Oseltamivir alone | Placebo comparator | Drug: Oseltamivir aloneoseltamivir 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FFA, clarithromycin, oseltamivirAlso: Antiviral combo2-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 | Drug | FFA, clarithromycin, oseltamivir |
| Oseltamivir aloneAlso: Antiviral2-day course of oseltamivir 75mg plus placebo capsules twice daily followed by oseltamivir 75mg twice daily for 3 days as control | Drug | Oseltamivir alone |
Primary outcome
Mortality
Time frame: 30 days from commencement of treatment intervention
30-day mortality
5 secondary outcomes
NPA
Time frame: 5 days post treatment
PSI
Time frame: 5 days post treatment
Hospitalisation
Time frame: Days of the subject hospitalised for the current admission up to 30 days
AE
Time frame: 2 weeks from subjects received treatment intervention
Long-term mortality
Time frame: 90 days from commencement of treatment intervention
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2019.
- Background: PubMed 27884765Hung 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.
- Background: PubMed 23450336Hung 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.
- Background: PubMed 20061398Li 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.
- Background: PubMed 21248066Hung 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.
- Individual participant dataSharing planned: Undecided
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Healthy Participants
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ivan Hung, MD FRCP principal investigator
The University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing FFA, clarithromycin, oseltamivir and Oseltamivir alone in people with Influenza A, run by The University of Hong Kong at 1 site in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Deborah Ho, BSc MSc (22554049, tipyin@yahoo.com.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mortality (time frame: 30 days from commencement of treatment intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03238612, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2019.