Azelastine Fluticasone Combination vs. Fluticasone

Allergic Rhinitis Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00845598
• Other study ID #: VAI04
• Status: Withdrawn
• Phase: Phase 4
• First received: February 17, 2009
• Last updated: June 11, 2012
• Start date: August 2010
• Est. completion date: August 2011

Study information

• Verified date: June 2012
• Source: University of Dundee
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Allergic Rhinitis
• Rhinitis

Intervention

Drug:
• Azelastine , fluticasone
Azelastine Hydrochloride BP 0.10% w/v AND Fluticasone propionate BP 0.0357% w/v as combination 1 squirt in each nostril twice daily
• Fluticasone propionate
Fluticasone propionate 0.05% w/w 2 squirts in each nostril (50 µg per squirt)

Locations

Country	Name	City	State
United Kingdom	Ninewells Hospital and Medical School	Dundee
United Kingdom	Perth Royal Infirmary	Perth

Sponsors (1)

Lead Sponsor	Collaborator
University of Dundee

Country where clinical trial is conducted

United Kingdom, 

References & Publications (8)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum percentage fall in PNIF after 400mg/ml of AMP nasal challenge between both groups.		0, 2 weeks, 4 weeks, 6 weeks, 8 weeks	No
Secondary	60 minute recovery to AMP challenge		0, 2 weeks, 4 weeks, 6 weeks, 8 weeks	No
Secondary	Mini RQLQ		0, 2 weeks, 4 weeks, 6 weeks, 8 weeks	No
Secondary	Global visual analogue scale		0, 2 weeks, 4 weeks, 6 weeks, 8 weeks	No
Secondary	Nasal lavage for cytokines		0, 2 weeks, 4 weeks, 6 weeks, 8 weeks	No
Secondary	Overnight urinary cortisol creatinine ratio		0, 2 weeks, 4 weeks, 6 weeks, 8 weeks	Yes
Secondary	Domiciliary diary cards		2 week treatment periods	No