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

NCT01779570 | Completed Phase 4

• 1 other identifier: RGC CUHK468112
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 2

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.

Conditions

Influenza; Lower Respiratory Tract Infection

Keywords

Influenza; Macrolide; Anti-inflammatory

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• viral clearance

  within 10 days post-intervention

Other Outcomes (1)

• time to recovery

  within 10 days post-intervention

Study Arms (2)

Macrolide treatment

EXPERIMENTAL

Azithromycin 500 mg daily for 5 days

Drug: Macrolide treatment

No macrolide treatment

NO INTERVENTION

No azithromycin

Interventions

Macrolide treatment DRUG

Macrolide treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (2)

Prince of Wales Hospital

Hong Kong, Hong Kong

Location

Princess Margaret Hospital

Hong Kong, Hong Kong

Location

Related Publications (12)

• 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.

  PMID: 23074315 BACKGROUND

• Chan 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.

  PMID: 22927451 BACKGROUND

• Lee 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.

  PMID: 22311561 BACKGROUND

• Lee 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.

  PMID: 22022504 BACKGROUND

• Lee 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.

  PMID: 21606532 BACKGROUND

• Lee 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.

  PMID: 21447873 BACKGROUND

• Lee 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.

  PMID: 20522848 BACKGROUND

• Hui 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.

  PMID: 20022969 BACKGROUND

• Lee 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.

  PMID: 19591575 BACKGROUND

• Lee 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.

  PMID: 17712756 BACKGROUND

• Lee 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.

  PMID: 17668558 BACKGROUND

• Lee 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.

  PMID: 28535933 DERIVED

Related Links

• Division of Infectious Diseases, Department of Medicine and Therapeutics, The Chinese University of Hong Kong

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Study Officials

• Nelson LS Lee, MD

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 29, 2013
• First Posted: January 30, 2013
• Study Start: February 1, 2013
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: July 27, 2016

Record last verified: 2016-07

Locations

HK (2)