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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05955885




Registration number
NCT05955885
Ethics application status
Date submitted
11/07/2023
Date registered
21/07/2023
Date last updated
25/07/2023

Titles & IDs
Public title
Effect of Over-the-counter NSAIDS on Cough Reflex Sensitivity in Patients With Upper Respiratory Tract Infections
Scientific title
Effect of Over-the-counter Non-steroidal Anti-inflammatory Treatments on Cough Reflex Sensitivity in Subjects With Upper Respiratory Tract Infection
Secondary ID [1] 0 0
25925
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cough 0 0
Upper Respiratory Tract Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Sexually transmitted infections
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 0 0 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Flurbiprofen Oral Lozenge
Treatment: Drugs - Difflam
Treatment: Drugs - Flurbiprofen 8.75 MG

Experimental: Flurbiprofen Oral Lozenge - 30 participants will be asked to suck one (1) flurbiprofen 8.75 mg honey and lemon lozenge (tradename: Strepfen) until dissolved.

Placebo comparator: Placebo lozenge - 30 participants will be asked to suck one (1) non-medicated Difflam Soothing Drops + Immune Support Honey \& Lemon flavour lozenge until dissolved.

Experimental: Flurbiprofen 8.75 MG - 30 participants will be asked to perform three (3) oral actuations (2.91 mg per actuation) of flurbiprofen 8.75mg spray.

Other: Low dose flurbiprofen spray - 30 participants will be asked to perform one (1) oral actuation of flurbiprofen 8.75 mg spray, equivalent to a 2.91mg dosage. This will serve a a low dose control as there is no placebo spray available.


Treatment: Drugs: Flurbiprofen Oral Lozenge
This commercially available, over-the-counter lozenge manufactured by Reckitt Benckiser contains flurbiprofen as the active ingredient and is registered for the short-term treatment of sore throat associated with upper respiratory tract infections in people over the age of 12 years.

Treatment: Drugs: Difflam
This is a non-medicated, control lozenge that is the same flavour as the experimental lozenge that is marketed to help soothe dry, tickly throats while supporting the body's immune health.

Treatment: Drugs: Flurbiprofen 8.75 MG
This commercially available, over-the-counter spray manufactured by Reckitt Benckiser contains flurbiprofen as the active ingredient and is registered for the short-term treatment of sore throat associated with upper respiratory tract infections in people over the age of 12 years. It requires 3 actuations of the spray to deliver the full 8.75 dose. Here, a low dose control can be delivered by only performing 1 actuation of the spray.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in objective measures of cough sensitivity
Timepoint [1] 0 0
Cough challenge testing will be performed at baseline and 3 hours after intervention.
Secondary outcome [1] 0 0
Change in Cold Symptoms Questionnaire (CSQ) score
Timepoint [1] 0 0
Participant self-reports using the Cold Symptoms Questionnaire at baseline and every 30 min after invention until 3 hours has elapsed.
Secondary outcome [2] 0 0
Change in levels of inflammatory markers in nasal fluid samples
Timepoint [2] 0 0
Nasal fluid samples will be taken at baseline and at 3 hours post-intervention.
Secondary outcome [3] 0 0
Change in levels of inflammatory markers in saliva samples
Timepoint [3] 0 0
Saliva samples will be taken at baseline and at 3 hours post-intervention.
Secondary outcome [4] 0 0
Change in levels of inflammatory markers in pharyngeal lavage samples
Timepoint [4] 0 0
Pharyngeal lavage samples will be taken at baseline and at 3 hours post-intervention.
Secondary outcome [5] 0 0
Patients' Global Impression of Change score
Timepoint [5] 0 0
Participants self-report using the Patients' Global Impression of Change score at 3 hours post-intervention.

Eligibility
Key inclusion criteria
* An onset of any 2 URTI symptoms in past 3-5 days, such as a sore throat, fever, coughing, coughing up phlegm, sneezing, and runny nose;
* A current cough or urge-to-cough rated at least 5 in severity and/or ranking cough as subject's most bothersome symptom on Cold Symptoms Questionnaire (CSQ);
* A feeling of sickness interfering with their daily life, rated as at least mildly;
* A cough consistent with acute cough - i.e., cough onset with URTI and not ongoing, chronic cough;
* Written informed consent and a willingness and ability to comply with the study protocol.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
* A pre-existing chronic lung disease (asthma, COPD, chronic bronchitis etc), to exclude these as causes for cough;
* The use of inhaled or systemic steroids / broncho-active medication, ACE inhibitors, oral or inhaled antihistamines, opiates, gabapentin, tricyclic antidepressants (current or within the past 3 months), as these will alter airway inflammatory profiles and/ or cough sensitivity;
* A current cigarette or marijuana smoker/vaper, recreational drug user, or have given up smoking/vaping within the last 12 months, or a former smoker with greater than 20 pack-years, alter airway inflammatory profiles and/ or cough sensitivity;
* Pre-existing chronic cough (cough persisting for more than 8 weeks): unexplained chronic cough (UCC) or refractory chronic cough (RCC) associated with or without a pre-existing condition (GERD, rhinitis, etc), as we are studying acute cough;
* Prior experience of an allergic or bad reaction to capsaicin or chilli (which is rare);
* Prior experience an allergic or bad reaction to a non-steroidal anti-inflammatory drug (NSAID) such as ibuprofen;
* Ongoing or history of stomach ulcer, impaired kidney or liver function, or heart failure;
* Pregnancy, lactation or actively trying to become pregnant;
* Currently taking other products with flurbiprofen, aspirin or other anti-inflammatory medicines;
* Evidence of COVID-19 positivity, either during the COVID Rapid Antigen Test administered on the day of assessment or have informed us that they have become positive in the 24-48 hours after the testing session (i.e., participants who were likely positive during assessment but under the detection threshold);
* Participants who cannot provide informed voluntary consent.

Study design
Purpose of the study
Other
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Phase 0
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2024
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
University of Melbourne - Carlton
Recruitment postcode(s) [1] 0 0
3010 - Carlton

Funding & Sponsors
Primary sponsor type
Other
Name
University of Melbourne
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Reckitt Benckiser LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The goal of this mechanism of disease study is to investigate the effect of flurbiprofen, a non-steroidal anti-inflammatory drug (NSAID), on the cough hypersensitivity associated with upper respiratory tract infections (URTI).

The main questions it aims to answer are:

* Q1: Does a single treatment with an approved therapeutic dose of flurbiprofen, an NSAID that prevents the production of prostaglandins, acutely reduce objective measures of cough hypersensitivity in participants with URTI?
* Q2: Is the effect of flurbiprofen on cough hypersensitivity in URTI related to participant subjective ratings of acute cough severity?
* Q3: Is the effect of flurbiprofen on cough hypersensitivity in URTI related to the levels of prostaglandins or other inflammatory markers measurable in upper airway secretions?

Participants will be asked to undergo cough challenge testing, complete quality of life questionnaires, and have their nasal fluid, saliva and pharyngeal secretions sampled before and after a single treatment with flurbiprofen in the form of a lozenge or spray. Participants in the comparator arms of the study will instead receive a placebo lozenge or low dose flurbiprofen spray.
Trial website
https://clinicaltrials.gov/study/NCT05955885
Trial related presentations / publications
Mazzone SB, Farrell MJ. Heterogeneity of cough neurobiology: Clinical implications. Pulm Pharmacol Ther. 2019 Apr;55:62-66. doi: 10.1016/j.pupt.2019.02.002. Epub 2019 Feb 11.
Farrell MJ, Mazzone SB. Are neural pathways processing airway inputs sensitized in patients with cough hypersensitivity? Pulm Pharmacol Ther. 2019 Aug;57:101806. doi: 10.1016/j.pupt.2019.101806. Epub 2019 May 15.
Dicpinigaitis PV. Effect of viral upper respiratory tract infection on cough reflex sensitivity. J Thorac Dis. 2014 Oct;6(Suppl 7):S708-11. doi: 10.3978/j.issn.2072-1439.2013.12.02.
Driessen AK, McGovern AE, Narula M, Yang SK, Keller JA, Farrell MJ, Mazzone SB. Central mechanisms of airway sensation and cough hypersensitivity. Pulm Pharmacol Ther. 2017 Dec;47:9-15. doi: 10.1016/j.pupt.2017.01.010. Epub 2017 Jan 27.
Renner B, Mueller CA, Shephard A. Environmental and non-infectious factors in the aetiology of pharyngitis (sore throat). Inflamm Res. 2012 Oct;61(10):1041-52. doi: 10.1007/s00011-012-0540-9. Epub 2012 Aug 14.
Lambkin-Williams R, Mann A, Shephard A. Inhibition of viral and bacterial trigger-stimulated prostaglandin E2 by a throat lozenge containing flurbiprofen: An in vitro study using a human respiratory epithelial cell line. SAGE Open Med. 2020 Sep 24;8:2050312120960568. doi: 10.1177/2050312120960568. eCollection 2020.
Schachtel BP, Homan HD, Gibb IA, Christian J. Demonstration of dose response of flurbiprofen lozenges with the sore throat pain model. Clin Pharmacol Ther. 2002 May;71(5):375-80. doi: 10.1067/mcp.2002.124079.
Schachtel B, Aspley S, Shephard A, Shea T, Smith G, Sanner K, Savino L, Rezuke J, Schachtel E. Onset of action of a lozenge containing flurbiprofen 8.75 mg: a randomized, double-blind, placebo-controlled trial with a new method for measuring onset of analgesic activity. Pain. 2014 Feb;155(2):422-428. doi: 10.1016/j.pain.2013.11.001. Epub 2013 Nov 12.
Public notes

Contacts
Principal investigator
Name 0 0
Stuart Mazzone, PhD
Address 0 0
University of Melbourne
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Stuart Mazzone, PhD
Address 0 0
Country 0 0
Phone 0 0
+61383446457
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05955885