InfluenzaPhase 4NCT01779570
Anti-inflammatory Effects of Macrolide Treatment in Influenza Lower Respiratory Tract Infections
A Phase 4 study testing Macrolide treatment in people with Influenza and Lower Respiratory Tract Infection, run by Chinese University of Hong Kong at 2 sites in Hong Kong.
Trial summary
Influenza lower respiratory tract infection (LRTI) is a major cause of morbidity and mortality worldwide. While viral replication can be suppressed by antiviral treatment, excessive inflammatory responses, which are increasingly recognized to contribute to severe influenza complications, remain unopposed. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Influenza, Lower Respiratory Tract Infection
- What is being tested?
- Macrolide treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 2 sitesHong Kong
- Study dates
- Feb 2013to Apr 2016
- Phase
- Phase 4
- 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
- established influenza A or B infection by virologic tests
- age >/=18 years
- present within 4 days from illness onset
- clinical evidence of LRTI and require hospital care
- require antiviral (oseltamivir) treatment
- able to provide written, informed consent.
Who cannot join
- patients on immunosuppressants
- pregnant or lactating woman
- known hepatic failure, end-stage renal failure, cardiac arrhythmia (e.g. prolonged corrected QT interval >450 msec)
- known contraindications to azithromycin (e.g. allergic reaction)
- lack of consent for study.
Trial locations and contacts
2 sites in 1 country.
Hong Kong2 sites
Prince of Wales Hospital
Hong Kong
Princess Margaret Hospital
Hong Kong
About this study
Influenza lower respiratory tract infection (LRTI) is a major cause of morbidity and mortality worldwide. While viral replication can be suppressed by antiviral treatment, excessive inflammatory responses, which are increasingly recognized to contribute to severe influenza complications, remain unopposed. Macrolides have been used widely to treat community-acquired pneumonia, and shown to exert anti-inflammatory effects in other respiratory diseases, providing clinical benefits. In this randomized, open-label, multicenter study, we aim to investigate the anti-inflammatory effects of macrolide treatment in influenza LRTI. Its impacts on the cytokine response, viral clearance, symptoms and disease resolution will be studied. Such results may lead to the development of new therapeutic approaches against severe influenza infection, and provide better insights into disease pathogenesis.
Read the detailed description
Objectives: (1) We aim to investigate the anti-inflammatory effects of macrolide treatment in patients with influenza LRTI and the impact on viral clearance. (2) To investigate the impact of macrolide treatment on influenza symptom and disease resolution.
Design: A randomized, open-label, multicenter study.
Settings: Acute medical facilities in 3 general public hospitals in Hong Kong.
Subjects, Sampling and Intervention: Adult (>/=18 years) patients hospitalized for virologically confirmed influenza LRTI who fulfill the inclusion/exclusion criteria will be randomized to receive (1) azithromycin 500 mg p.o. for 5 days (in addition to antiviral, as part of usual care), or (2) no azithromycin (ie, antiviral alone, part of usual care) after informed consent. Serial blood samples will be collected for cytokine/inflammatory response assays. Serial nasopharyngeal swabs will be collected to assess for viral clearance. Symptoms, clinical progress, radiography and adverse events will be monitored.
- Conditions
- Influenza, Lower Respiratory Tract Infection
- Being tested
- Macrolide treatment
- Keywords
- Influenza, Macrolide, Anti-inflammatory
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Macrolide treatmentDrug
| Study group | Role | What they receive |
|---|---|---|
| Macrolide treatment | Experimental | Azithromycin 500 mg daily for 5 days Receives: Drug: Macrolide treatment |
| No macrolide treatment | No intervention | No azithromycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
cytokine and inflammatory responses
Serial measurements of selected cytokines/chemokines (e.g. interleukin-6, CXCL8) and proinflammatory molecules (e.g. DAMPs)
Measured: within 10 days post-intervention
Secondary outcomes (1)
viral clearance
Viral RNA and culture negativity in serially collected respiratory tract specimens
Measured: within 10 days post-intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2013 (estimated)
- Study startFeb 2013
- Primary completionApr 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- More trials run by Chinese 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nelson Lee, Chinese University of Hong Kong
- Investigators
- Nelson LS Lee, MD, Principal investigator, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01779570
- Sponsor's protocol ID
- RGC CUHK468112
- Status last verified
- Jul 2016
- First submitted
- 29 Jan 2013
- Last updated
- 27 Jul 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Chan PK, Chan MC, Cheung JL, Lee N, Leung TF, Yeung AC, Wong MC, Ngai KL, Nelson EA, Hui DS. Influenza B lineage circulation and hospitalization rates in a subtropical city, Hong Kong, 2000-2010. Clin Infect Dis. 2013 Mar;56(5):677-84. doi: 10.1093/cid/cis885. Epub 2012 Oct 16.
PubMed 23074315Chan PK, Lee N, Zaman M, Adisasmito W, Coker R, Hanshaoworakul W, Gasimov V, Oner AF, Dogan N, Tsang O, Phommasack B, Touch S, Bamgboye E, Swenson A, Toovey S, Dreyer NA. Determinants of antiviral effectiveness in influenza virus A subtype H5N1. J Infect Dis. 2012 Nov;206(9):1359-66. doi: 10.1093/infdis/jis509. Epub 2012 Aug 20.
PubMed 22927451Lee N, Ison MG. Diagnosis, management and outcomes of adults hospitalized with influenza. Antivir Ther. 2012;17(1 Pt B):143-57. doi: 10.3851/IMP2059. Epub 2012 Feb 3.
PubMed 22311561Lee N, Wong CK, Chan PK, Chan MC, Wong RY, Lun SW, Ngai KL, Lui GC, Wong BC, Lee SK, Choi KW, Hui DS. Cytokine response patterns in severe pandemic 2009 H1N1 and seasonal influenza among hospitalized adults. PLoS One. 2011;6(10):e26050. doi: 10.1371/journal.pone.0026050. Epub 2011 Oct 13.
PubMed 22022504Lee N, Chan PK, Lui GC, Wong BC, Sin WW, Choi KW, Wong RY, Lee EL, Yeung AC, Ngai KL, Chan MC, Lai RW, Yu AW, Hui DS. Complications and outcomes of pandemic 2009 Influenza A (H1N1) virus infection in hospitalized adults: how do they differ from those in seasonal influenza? J Infect Dis. 2011 Jun 15;203(12):1739-47. doi: 10.1093/infdis/jir187.
PubMed 21606532Lee N, Chan PK, Wong CK, Wong KT, Choi KW, Joynt GM, Lam P, Chan MC, Wong BC, Lui GC, Sin WW, Wong RY, Lam WY, Yeung AC, Leung TF, So HY, Yu AW, Sung JJ, Hui DS. Viral clearance and inflammatory response patterns in adults hospitalized for pandemic 2009 influenza A(H1N1) virus pneumonia. Antivir Ther. 2011;16(2):237-47. doi: 10.3851/IMP1722.
PubMed 21447873Lee N, Choi KW, Chan PK, Hui DS, Lui GC, Wong BC, Wong RY, Sin WY, Hui WM, Ngai KL, Cockram CS, Lai RW, Sung JJ. Outcomes of adults hospitalised with severe influenza. Thorax. 2010 Jun;65(6):510-5. doi: 10.1136/thx.2009.130799.
PubMed 20522848Hui DS, Lee N, Chan PK. Clinical management of pandemic 2009 influenza A(H1N1) infection. Chest. 2010 Apr;137(4):916-25. doi: 10.1378/chest.09-2344. Epub 2009 Dec 18.
PubMed 20022969Lee N, Chan PK, Hui DS, Rainer TH, Wong E, Choi KW, Lui GC, Wong BC, Wong RY, Lam WY, Chu IM, Lai RW, Cockram CS, Sung JJ. Viral loads and duration of viral shedding in adult patients hospitalized with influenza. J Infect Dis. 2009 Aug 15;200(4):492-500. doi: 10.1086/600383.
PubMed 19591575Lee N, Wong CK, Chan PK, Lun SW, Lui G, Wong B, Hui DS, Lam CW, Cockram CS, Choi KW, Yeung AC, Tang JW, Sung JJ. Hypercytokinemia and hyperactivation of phospho-p38 mitogen-activated protein kinase in severe human influenza A virus infection. Clin Infect Dis. 2007 Sep 15;45(6):723-31. doi: 10.1086/520981. Epub 2007 Aug 8.
PubMed 17712756Lee N, Chan PK, Choi KW, Lui G, Wong B, Cockram CS, Hui DS, Lai R, Tang JW, Sung JJ. Factors associated with early hospital discharge of adult influenza patients. Antivir Ther. 2007;12(4):501-8.
PubMed 17668558Lee N, Wong CK, Chan MCW, Yeung ESL, Tam WWS, Tsang OTY, Choi KW, Chan PKS, Kwok A, Lui GCY, Leung WS, Yung IMH, Wong RYK, Cheung CSK, Hui DSC. Anti-inflammatory effects of adjunctive macrolide treatment in adults hospitalized with influenza: A randomized controlled trial. Antiviral Res. 2017 Aug;144:48-56. doi: 10.1016/j.antiviral.2017.05.008. Epub 2017 May 20.
PubMed 28535933
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anti-inflammatory Effects of Macrolide Treatment in Influenza Lower Respiratory Tract Infections
- ClinicalTrials.gov ID
- NCT01779570
- Acronym / sponsor ID
- RGC CUHK468112
- Conditions
- Influenza, Lower Respiratory Tract Infection
- Keywords
- Influenza, Macrolide, Anti-inflammatory
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Study start
- Feb 2013
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 30 Jan 2013 (estimated)
- 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.
Influenza lower respiratory tract infection (LRTI) is a major cause of morbidity and mortality worldwide. While viral replication can be suppressed by antiviral treatment, excessive inflammatory responses, which are increasingly recognized to contribute to severe influenza complications, remain unopposed. Macrolides have been used widely to treat community-acquired pneumonia, and shown to exert anti-inflammatory effects in other respiratory diseases, providing clinical benefits. In this randomized, open-label, multicenter study, we aim to investigate the anti-inflammatory effects of macrolide treatment in influenza LRTI. Its impacts on the cytokine response, viral clearance, symptoms and disease resolution will be studied. Such results may lead to the development of new therapeutic approaches against severe influenza infection, and provide better insights into disease pathogenesis.
Detailed description
Objectives: (1) We aim to investigate the anti-inflammatory effects of macrolide treatment in patients with influenza LRTI and the impact on viral clearance. (2) To investigate the impact of macrolide treatment on influenza symptom and disease resolution.
Design: A randomized, open-label, multicenter study.
Settings: Acute medical facilities in 3 general public hospitals in Hong Kong.
Subjects, Sampling and Intervention: Adult (>/=18 years) patients hospitalized for virologically confirmed influenza LRTI who fulfill the inclusion/exclusion criteria will be randomized to receive (1) azithromycin 500 mg p.o. for 5 days (in addition to antiviral, as part of usual care), or (2) no azithromycin (ie, antiviral alone, part of usual care) after informed consent. Serial blood samples will be collected for cytokine/inflammatory response assays. Serial nasopharyngeal swabs will be collected to assess for viral clearance. Symptoms, clinical progress, radiography and adverse events will be monitored.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Macrolide treatment | Experimental | Drug: Macrolide treatmentAzithromycin 500 mg daily for 5 days |
| No macrolide treatment | No intervention | –No azithromycin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- established influenza A or B infection by virologic tests
- age >/=18 years
- present within 4 days from illness onset
- clinical evidence of LRTI and require hospital care
- require antiviral (oseltamivir) treatment
Key exclusion criteria (5 listed)
- patients on immunosuppressants
- pregnant or lactating woman
- known hepatic failure, end-stage renal failure, cardiac arrhythmia (e.g. prolonged corrected QT interval >450 msec)
- known contraindications to azithromycin (e.g. allergic reaction)
- lack of consent for study.
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 |
|---|---|---|
| Macrolide treatment | Drug | Macrolide treatment |
Primary outcome
cytokine and inflammatory responses
Time frame: within 10 days post-intervention
Serial measurements of selected cytokines/chemokines (e.g. interleukin-6, CXCL8) and proinflammatory molecules (e.g. DAMPs)
1 secondary outcome
viral clearance
Time frame: within 10 days post-intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2016.
- Background: PubMed 23074315Chan PK, Chan MC, Cheung JL, Lee N, Leung TF, Yeung AC, Wong MC, Ngai KL, Nelson EA, Hui DS. Influenza B lineage circulation and hospitalization rates in a subtropical city, Hong Kong, 2000-2010. Clin Infect Dis. 2013 Mar;56(5):677-84. doi: 10.1093/cid/cis885. Epub 2012 Oct 16.
- Background: PubMed 22927451Chan PK, Lee N, Zaman M, Adisasmito W, Coker R, Hanshaoworakul W, Gasimov V, Oner AF, Dogan N, Tsang O, Phommasack B, Touch S, Bamgboye E, Swenson A, Toovey S, Dreyer NA. Determinants of antiviral effectiveness in influenza virus A subtype H5N1. J Infect Dis. 2012 Nov;206(9):1359-66. doi: 10.1093/infdis/jis509. Epub 2012 Aug 20.
- Background: PubMed 22311561Lee N, Ison MG. Diagnosis, management and outcomes of adults hospitalized with influenza. Antivir Ther. 2012;17(1 Pt B):143-57. doi: 10.3851/IMP2059. Epub 2012 Feb 3.
- Background: PubMed 22022504Lee N, Wong CK, Chan PK, Chan MC, Wong RY, Lun SW, Ngai KL, Lui GC, Wong BC, Lee SK, Choi KW, Hui DS. Cytokine response patterns in severe pandemic 2009 H1N1 and seasonal influenza among hospitalized adults. PLoS One. 2011;6(10):e26050. doi: 10.1371/journal.pone.0026050. Epub 2011 Oct 13.
- Background: PubMed 21606532Lee N, Chan PK, Lui GC, Wong BC, Sin WW, Choi KW, Wong RY, Lee EL, Yeung AC, Ngai KL, Chan MC, Lai RW, Yu AW, Hui DS. Complications and outcomes of pandemic 2009 Influenza A (H1N1) virus infection in hospitalized adults: how do they differ from those in seasonal influenza? J Infect Dis. 2011 Jun 15;203(12):1739-47. doi: 10.1093/infdis/jir187.
- Background: PubMed 21447873Lee N, Chan PK, Wong CK, Wong KT, Choi KW, Joynt GM, Lam P, Chan MC, Wong BC, Lui GC, Sin WW, Wong RY, Lam WY, Yeung AC, Leung TF, So HY, Yu AW, Sung JJ, Hui DS. Viral clearance and inflammatory response patterns in adults hospitalized for pandemic 2009 influenza A(H1N1) virus pneumonia. Antivir Ther. 2011;16(2):237-47. doi: 10.3851/IMP1722.
- Background: PubMed 20522848Lee N, Choi KW, Chan PK, Hui DS, Lui GC, Wong BC, Wong RY, Sin WY, Hui WM, Ngai KL, Cockram CS, Lai RW, Sung JJ. Outcomes of adults hospitalised with severe influenza. Thorax. 2010 Jun;65(6):510-5. doi: 10.1136/thx.2009.130799.
- Background: PubMed 20022969Hui DS, Lee N, Chan PK. Clinical management of pandemic 2009 influenza A(H1N1) infection. Chest. 2010 Apr;137(4):916-25. doi: 10.1378/chest.09-2344. Epub 2009 Dec 18.
- Background: PubMed 19591575Lee N, Chan PK, Hui DS, Rainer TH, Wong E, Choi KW, Lui GC, Wong BC, Wong RY, Lam WY, Chu IM, Lai RW, Cockram CS, Sung JJ. Viral loads and duration of viral shedding in adult patients hospitalized with influenza. J Infect Dis. 2009 Aug 15;200(4):492-500. doi: 10.1086/600383.
- Background: PubMed 17712756Lee N, Wong CK, Chan PK, Lun SW, Lui G, Wong B, Hui DS, Lam CW, Cockram CS, Choi KW, Yeung AC, Tang JW, Sung JJ. Hypercytokinemia and hyperactivation of phospho-p38 mitogen-activated protein kinase in severe human influenza A virus infection. Clin Infect Dis. 2007 Sep 15;45(6):723-31. doi: 10.1086/520981. Epub 2007 Aug 8.
- Background: PubMed 17668558Lee N, Chan PK, Choi KW, Lui G, Wong B, Cockram CS, Hui DS, Lai R, Tang JW, Sung JJ. Factors associated with early hospital discharge of adult influenza patients. Antivir Ther. 2007;12(4):501-8.
- Derived from this study: PubMed 28535933Lee N, Wong CK, Chan MCW, Yeung ESL, Tam WWS, Tsang OTY, Choi KW, Chan PKS, Kwok A, Lui GCY, Leung WS, Yung IMH, Wong RYK, Cheung CSK, Hui DSC. Anti-inflammatory effects of adjunctive macrolide treatment in adults hospitalized with influenza: A randomized controlled trial. Antiviral Res. 2017 Aug;144:48-56. doi: 10.1016/j.antiviral.2017.05.008. Epub 2017 May 20.
- Division of Infectious Diseases, Department of Medicine and Therapeutics, The Chinese University of Hong KongLink provided by the sponsor.
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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.
Nelson LS Lee, MD principal investigator
Chinese University of Hong Kong
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Macrolide treatment in people with Influenza and Lower Respiratory Tract Infection, run by Chinese University of Hong Kong at 2 sites 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 6 inclusion and 5 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: finished, as of the sponsor's last update on 27 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
cytokine and inflammatory responses (time frame: within 10 days post-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 NCT01779570, which also lists 12 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 27 Jul 2016.