Clinical trial NCT03824847: Immunomodulatory Effect of Macrolides in Naturally Occurring Influenza Virus Infections in the Community
Official title: Immunomodulatory Effect of Macrolides in Naturally Occurring Influenza Virus Infections in the Community
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE4
Conditions: Influenza, Human
Keywords: Macrolides
Immunomodulation
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
First posted: 2019-01-31
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators propose a double-blind randomised placebo-controlled study in naturally occurring influenza virus infections in the community setting to compare the impact of a short course of clarithromycin versus placebo, on the clinical course, viral shedding, immunomodulation, and the antimicrobial resistance pattern of respiratory bacterial carriage of the patients.

Detailed description: Background: Influenza continues to pose an imminent threat to public health through seasonal epidemics and occasion pandemics with significant impact on morbidity and mortality. Increasing attention has also been paid in recent years to the potential benefit of immunomodulatory effect of macrolide antibiotics in the management of influenza virus infection.

Aims: To study the immunomodulatory effects of a short course of clarithromycin in naturally occurring influenza virus infection.

Design and subjects: The study is a double-blind, randomised controlled trial. One hundred adults aged 18-60 years will be recruited when they present with symptoms of acute respiratory infection within 48 hours of symptoms onset to university health clinics, and being tested positive with a QuickVue/Sofia (Quidel Corp., San Diego, CA) rapid influenza test. Consented patients tested positive with the rapid test will receive their clinical consultation and prescriptions as indicated as usual, and being randomised to receive either clarithromycin (250mg) or placebo (in a ratio of 1:1) taken twice daily orally for three days. Blood specimen, nasal and throat swabs will be collected on the same day (day 1). They will be followed-up on day 4, day 7 and day 10 for further collection of nasal and throat swabs, and serum samples. A symptom diary will be kept by each participant for 10 days for monitoring the clinical course of the infection.

Study instruments: QuickVue/Sofia (Quidel Corp., San Diego, CA) rapid influenza test, symptom diary, blood specimen, nasal and throat swabs.

Interventions: Intervention group: clarithromycin; placebo group: placebo in identical packaging.

Main outcome measures: The primary outcomes of the study will compare the duration of illness, viral shedding, patterns of plasma cytokine/chemokine and antimicrobial resistance pattern of respiratory bacterial carriage between patients who were randomised to clarithromycin or placebo.

Analysis: Intention to treat.

Potential significance: This will be the first placebo-controlled RCT to investigate the immunomodulatory effect of macrolide antibiotics in the management of influenza virus infection, in terms of its impact on the duration of illness, viral shedding, patterns of plasma cytokine/chemokine and antimicrobial resistance pattern of respiratory bacterial carriage. Findings from this study will have important contribution to our understanding on the potential immunomodulatory effect of macrolides, and help to inform the appropriate clinical management approach, and the potential

Eligibility criteria: Inclusion Criteria:

* Adults aged between 18-60
* Presenting with symptoms of acute URTI (at least two among the following symptoms: body temperature ≥37.8°C, cough, rhinorrhea, sore throat, headache, myalgia/arthralgia) to university health clinics within 48 hours of illness onset.

Exclusion Criteria:

* Allergy to clarithromycin or any other macrolides or the ingredients in the tablets, which include microcrystalline cellulose, croscarmelose sodium, magnesium stearate and povidon will be excluded.
* Patients with a history of chronic liver disease, or any active lung, heart or renal diseases requiring regular medication, or any underlying immunocompromised condition or receiving immunosuppressive agents will also be excluded.

Primary outcomes:
measure: Time from recruitment to cessation of clinical illness
timeFrame: 10 days
measure: Time from recruitment to cessation of viral shedding
timeFrame: 10 days
Secondary outcomes:
measure: Duration and severity of individual symptoms
timeFrame: 10 days
measure: Incidence of secondary complications
timeFrame: 28 days
measure: Health-related quality of life
timeFrame: 28 days
measure: Geometric mean rise in antibody titre against the infecting type or subtype of influenza virus
timeFrame: 28 days
measure: Changes in blood immunity (Cytokine/chemokine and pro-inflammatory mediators)
timeFrame: 7 days
measure: Change in the carriage rate of common respiratory bacterial pathogen
timeFrame: 7 days
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: School of Public Health, The University of Hong Kong
Study officials:
affiliation: School of Public Health, The University of Hong Kong
name: Dennis KM Ip, MD
role: PRINCIPAL_INVESTIGATOR
References: