Azelastine Fluticasone Combination vs. Fluticasone

Condition(s) targeted: Allergic Rhinitis

Intervention: Azelastine , fluticasone (Drug); Fluticasone propionate (Drug)

Phase: Phase 4

Status: Not yet recruiting

Sponsored by: University of Dundee

Official(s) and/or principal investigator(s):
Sriram Vaidyanathan, MBBS, Principal Investigator, Affiliation: University of Dundee
Brian Lipworth, MD, FRCP, Study Director, Affiliation: University of Dundee

Overall contact:
Sriram Vaidyanathan, MBBS, Phone: +44 1382496355, Email: s.vaidyanathan@dundee.ac.uk

The purpose of this study is to see how a combination spray of azelastine and fluticasone (antihistamine and steroid) compares with a steroid nasal spray (fluticasone) alone in allergic rhinitis i. e. does azelastine permit the use of lesser steroid dose (steroid sparing effect) to achieve the same benefit.

Official title: A Proof of Concept Study to Evaluate Comparative Efficacy of an Azelastine/Fluticasone Combination Nasal Spray vs. Twice the Dose of Fluticasone in Persistent Allergic Rhinitis

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Maximum percentage fall in PNIF after 400mg/ml of AMP nasal challenge between both groups.

Secondary outcome:

60 minute recovery to AMP challenge

Mini RQLQ

Global visual analogue scale

Nasal lavage for cytokines

Overnight urinary cortisol creatinine ratio

Domiciliary diary cards

Detailed description: Allergic rhinitis (AR) is a major chronic respiratory disease with a prevalence approaching nearly 25% in the worldwide population. Allergic Rhinitis is a common and relatively undiagnosed public health problem and has been reported as being one of the ten most common causes for outpatient attendances to the general practitioner. Long term untreated allergic rhinitis may lead on to asthma. When exposed to allergens (pollen, house dust mite etc) in the atmosphere, the mast cells in the nose burst and an inflammatory response is triggered and patients experience sneezing, itching, blocked nose and running. These allergens may be used as provocation agents to recreate the disease symptoms to confirm the diagnosis of which allergens one is allergic to. However, there is a risk of allergic reactions in doing so. Adenosine monophosphate (AMP)achieves the same goal by stimulating the mast cells and causing them to burst without actually the risks of allergen provocation tests. Such tests are now commonplace in research and clinical medicine. Nasal steroids are considered to be the most potent medications for allergic rhinitis, particularly nasal blockage. Nasal antihistamines are also available but they act mainly to limit nasal running, itching and sneezing and have lesser effect on blockage. The other advantage is that they act very quickly while steroids take at least 72 hours to begin acting and weeks to achieve maximal benefit. Finally, they are free of significant short and long term side effects. Having said that nasal steroids are very safe and unlike inhaled or oral steroids have not been shown to cause systemic side effects in adults. Therefore, it is interesting to see if a combination of an antihistamine and nasal steroid would add their good qualities mentioned above and by the act of reducing the dose of steroid reduce their side effects. To do this we will use nasal AMP challenge as an outcome measure as we have done research studies for over a decade with. We will look at noninvasive nasal airflow parameters, nasal nitric oxide levels, and for safety we will look at the overnight urinary cortisol and creatinine ratio which is the most sensitive and noninvasive test of urine to quantify how much steroid has been absorbed in the blood stream.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Male of Female aged 18‐65 years.

- Persistent allergic rhinitis with or without asthma.

- Atopy to at least one allergen on SPT.

- Ability to give a written informed consent.

- Ability and willingness to comply with the requirements of the protocol.

Exclusion Criteria:

- Recent respiratory tract/sinus infection within the last 2 months. .

- Pregnancy, planned pregnancy or lactation.

- Known or suspected hypersensitivity to any of the IMP's.

- Concomitant use of medicines (prescribed, OTC or herbal) like alpha blockers that may

interfere with the trial.

- Nasal Polyposis grade 2+, Deviated nasal septum ≥ 50%

- The use of oral corticosteroids within the last 3 months.

Sriram Vaidyanathan, MBBS, Phone: +44 1382496355, Email: s.vaidyanathan@dundee.ac.uk

Ninewells Hospital and Medical School, Dundee DD1 9SY, United Kingdom

Perth Royal Infirmary, Perth PH1 1NX, United Kingdom

Related publications:

Bousquet J, Van Cauwenberge P, Khaltaev N; Aria Workshop Group; World Health Organization. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol. 2001 Nov;108(5 Suppl):S147-334. Review. No abstract available.

Nassef M, Shapiro G, Casale TB; Respiratory and Allergic Disease Foundation. Identifying and managing rhinitis and its subtypes: allergic and nonallergic components--a consensus report and materials from the Respiratory and Allergic Disease Foundation. Curr Med Res Opin. 2006 Dec;22(12):2541-8.

Nolte H, Nepper-Christensen S, Backer V. Unawareness and undertreatment of asthma and allergic rhinitis in a general population. Respir Med. 2006 Feb;100(2):354-62. Epub 2005 Jul 11.

Gupta R, Sheikh A, Strachan DP, Anderson HR. Burden of allergic disease in the UK: secondary analyses of national databases. Clin Exp Allergy. 2004 Apr;34(4):520-6.

Weiner JM, Abramson MJ, Puy RM. Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis: systematic review of randomised controlled trials. BMJ. 1998 Dec 12;317(7173):1624-9.

Meltzer EO, Weiler JM, Dockhorn RJ, Widlitz MD, Freitag JJ. Azelastine nasal spray in the management of seasonal allergic rhinitis. Ann Allergy. 1994 Apr;72(4):354-9.

Newson-Smith G, Powell M, Baehre M, Garnham SP, MacMahon MT. A placebo controlled study comparing the efficacy of intranasal azelastine and beclomethasone in the treatment of seasonal allergic rhinitis. Eur Arch Otorhinolaryngol. 1997;254(5):236-41.

Berger WE, Fineman SM, Lieberman P, Miles RM. Double-blind trials of azelastine nasal spray monotherapy versus combination therapy with loratadine tablets and beclomethasone nasal spray in patients with seasonal allergic rhinitis. Rhinitis Study Groups. Ann Allergy Asthma Immunol. 1999 Jun;82(6):535-41.

Starting date: August 2010
Last updated: January 11, 2010