Anti-inflammatory Effects of Macrolide Treatment in Influenza Lower Respiratory Tract Infections

Study Overview
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Brief Summary
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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
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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.

Official Title
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Anti-inflammatory Effects of Macrolide Treatment in Influenza Lower Respiratory Tract Infections

Conditions
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Influenza, Lower Respiratory Tract Infection

Intervention / Treatment
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* Drug: Macrolide treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Macrolide treatment<br>Azithromycin 500 mg daily for 5 days | Drug: Macrolide treatment<br> <br> |
| No Intervention: No macrolide treatment<br>No azithromycin | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cytokine and inflammatory responses | Serial measurements of selected cytokines/chemokines (e.g. interleukin-6, CXCL8) and proinflammatory molecules (e.g. DAMPs) | within 10 days post-intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| viral clearance | Viral RNA and culture negativity in serially collected respiratory tract specimens | within 10 days post-intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, Macrolide, Anti-inflammatory