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

Phase 4

Completed

• Conditions: Lower Respiratory Tract Infection; Influenza
• Interventions: Drug: Macrolide treatment

• Registration Number: NCT01779570
• Lead Sponsor: Chinese University of Hong Kong

Brief 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. 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 Timeline

• Study First Submitted: 2013-01-29
• Study First Submitted QC: 2013-01-29
• Study First Posted: 2013-01-30
• Study Start: 2013-02
• Primary Completion: 2016-04
• Study Completion: 2016-04
• Status Verified: 2016-07
• Last Update Submitted: 2016-07-25
• Last Update Posted: 2016-07-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 68

Inclusion Criteria

1. established influenza A or B infection by virologic tests
2. age >/=18 years
3. present within 4 days from illness onset
4. clinical evidence of LRTI and require hospital care
5. require antiviral (oseltamivir) treatment
6. able to provide written, informed consent.

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Exclusion Criteria

1. patients on immunosuppressants
2. pregnant or lactating woman
3. known hepatic failure, end-stage renal failure, cardiac arrhythmia (e.g. prolonged corrected QT interval >450 msec)
4. known contraindications to azithromycin (e.g. allergic reaction)
5. lack of consent for study.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Macrolide treatment	Macrolide treatment	Azithromycin 500 mg daily for 5 days

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
viral clearance	within 10 days post-intervention	Viral RNA and culture negativity in serially collected respiratory tract specimens

Trial Locations

Locations (2)

Princess Margaret Hospital; 🇭🇰 Hong Kong, Hong Kong

Prince of Wales Hospital; 🇭🇰 Hong Kong, Hong Kong