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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2016 by Chinese University of Hong Kong
Information provided by (Responsible Party):
Nelson Lee, Chinese University of Hong Kong Identifier:
First received: January 29, 2013
Last updated: January 26, 2016
Last verified: January 2016
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.

Condition Intervention Phase
Lower Respiratory Tract Infection
Drug: Macrolide treatment
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Anti-inflammatory Effects of Macrolide Treatment in Influenza Lower Respiratory Tract Infections

Resource links provided by NLM:

Further study details as provided by Chinese University of Hong Kong:

Primary Outcome Measures:
  • cytokine and inflammatory responses [ Time Frame: within 10 days post-intervention ] [ Designated as safety issue: No ]
    Serial measurements of selected cytokines/chemokines (e.g. interleukin-6, CXCL8) and proinflammatory molecules (e.g. DAMPs)

Secondary Outcome Measures:
  • viral clearance [ Time Frame: within 10 days post-intervention ] [ Designated as safety issue: No ]
    Viral RNA and culture negativity in serially collected respiratory tract specimens

Other Outcome Measures:
  • time to recovery [ Time Frame: within 10 days post-intervention ] [ Designated as safety issue: No ]
    e.g. time to symptom resolution, time to hospital discharge, etc

Estimated Enrollment: 100
Study Start Date: February 2013
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Macrolide treatment
Azithromycin 500 mg daily for 5 days
Drug: Macrolide treatment
No Intervention: No macrolide treatment
No azithromycin

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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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.

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01779570

Contact: Nelson LS Lee, MD
Contact: David SC Hui, MD

Hong Kong
Prince of Wales Hospital Recruiting
Hong Kong, Hong Kong
Contact: Nelson LS Lee, MD   
Contact: David SC Hui, MD   
Princess Margaret Hospital Recruiting
Hong Kong, Hong Kong
Contact: Owen TY Tsang, MD   
Sponsors and Collaborators
Chinese University of Hong Kong
Principal Investigator: Nelson LS Lee, MD Chinese University of Hong Kong
  More Information

Additional Information:

Responsible Party: Nelson Lee, Professor, Chinese University of Hong Kong Identifier: NCT01779570     History of Changes
Other Study ID Numbers: RGC CUHK468112 
Study First Received: January 29, 2013
Last Updated: January 26, 2016
Health Authority: Hong Kong: Joint CUHK-NTEC Clinical Research Ethics Committee

Keywords provided by Chinese University of Hong Kong:

Additional relevant MeSH terms:
Influenza, Human
Respiratory Tract Infections
Orthomyxoviridae Infections
RNA Virus Infections
Respiratory Tract Diseases
Virus Diseases
Anti-Inflammatory Agents
Pharmacologic Actions
Therapeutic Uses processed this record on February 04, 2016