The Addition of Montelukast to Fluticasone in the Treatment of Perennial Allergic Rhinitis

Study Description

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Brief Summary:

Some people with nasal allergy symptoms continue to have symptoms even after treatment with a nasal steroid spray. The purpose of this study is to see if these patients are helped by adding another medication (montelukast) to their treatment compared to placebo (a substance that looks like the active medication but does not contain the drug).

Condition or disease	Intervention/treatment	Phase
Rhinitis, Allergic, Perennial	Drug: Placebo; Drug: Montelukast; Drug: Fluticasone propionate	Phase 4

Detailed Description:

Clinicians frequently prescribe an oral H1 antihistamine for allergic rhinitis patients with residual symptoms after taking an intranasal steroid. Surprisingly, the only studies investigating this combination of drugs have failed to show added efficacy of the H1 receptor over the intranasal steroids alone. Adding montelukast, a leukotriene receptor antagonist, to an intranasal steroid has not been studied in a placebo controlled fashion. Wilson and colleagues, in an open study of patients with chronic rhinosinusitis, showed a benefit of adding montelukast.

The investigators would like to recruit perennially allergic subjects and place them on fluticasone for 2 weeks. Those subjects with residual symptoms would then be randomized to receive either placebo or montelukast in addition to continuing the fluticasone for an additional 2 weeks.

A positive study would support clinical practice and would serve as a preemptive strike against managed care plans that would not allow prescriptions for both drugs.

Hypothesis:

The addition of montelukast to treatment of a perennially allergic subject with an intranasal steroid is more effective at relieving symptoms than a placebo.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	102 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	The Addition of Montelukast to Fluticasone in the Treatment of Perennial Allergic Rhinitis
Study Start Date :	July 2005
Actual Primary Completion Date :	June 2008
Actual Study Completion Date :	January 2009

Arms and Interventions

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Arm	Intervention/treatment
Placebo Comparator: Fluticasone propionate + Placebo; Fluticasone propionate nasal spray - 2 sprays in each nostril once a day for 2 weeks (200 micrograms daily) Placebo - 10 mg po daily for 2 weeks	Drug: Placebo Drug: Fluticasone propionate; Other Name: flonase
Active Comparator: Fluticasone propionate + Montelukast; Fluticasone propionate nasal spray - 2 sprays in each nostril once a day for 2 weeks (200 micrograms daily) Montelukast - 10 mg po daily for 2 weeks	Drug: Montelukast; Other Name: singulair Drug: Fluticasone propionate; Other Name: flonase

Outcome Measures

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Primary Outcome Measures :

1. Change From Baseline in Total Nasal Symptom Score (TNSS) Over 2 Week Randomized Treatment Period [ Time Frame: Baseline and 2 weeks ]

   Patients recorded the severity of sneezing, runny nose, stuffy nose, and other symptoms (itchy nose/eyes and post-nasal drip) twice a day on a scale from 0 to 3 (0 = no symptoms, 1 = mild, 2 = moderate, and 3 = severe). The TNSS was calculated as the sum of all scores for morning and evening recordings with a range of 0 to 24.

   The baseline TNSS used in the analysis was the average of the symptom scores from the last 5 days of fluticasone propionate therapy prior to randomized treatment period.

   The change from baseline for each subsequent day of treatment was then calculated for each subject. So that each subject only had one observation, the average of these changes was calculated for each subject, and this summary measure was used in the analysis comparing the two treatment groups. We report the median and full range of these average changes for each group.

   A negative value indicates an improvement in symptoms.

Secondary Outcome Measures :

1. Change From Baseline in Sneezing Symptom Score Over 2 Week Randomized Treatment Period [ Time Frame: Baseline and 2 weeks ]

   Patients recorded the severity of sneezing twice a day on a scale from 0 to 3 (0 = no symptoms, 1 = mild, 2 = moderate, and 3 = severe). The sneezing symptom score was calculated as the sum of all scores for morning and evening recordings with a range of 0 to 6.

   The baseline symptom score used in the analysis was the average of the symptom scores from the last 5 days of fluticasone propionate therapy prior to randomized treatment period.

   The change from baseline for each subsequent day of treatment was then calculated for each subject. So that each subject only had one observation, the average of these changes was calculated for each subject, and this summary measure was used in the analysis comparing the two treatment groups. We report the median and full range of these average changes for each group.

   A negative value indicates an improvement in symptoms.

2. Change From Baseline in Runny Nose Symptom Score Over 2 Week Randomized Treatment Period [ Time Frame: Baseline and 2 weeks ]

   Patients recorded the severity of runny nose twice a day on a scale from 0 to 3 (0 = no symptoms, 1 = mild, 2 = moderate, and 3 = severe). The runny nose symptom score was calculated as the sum of all scores for morning and evening recordings with a range of 0 to 6.

   The baseline symptom score used in the analysis was the average of the symptom scores from the last 5 days of fluticasone propionate therapy prior to randomized treatment period.

   The change from baseline for each subsequent day of treatment was then calculated for each subject. So that each subject only had one observation, the average of these changes was calculated for each subject, and this summary measure was used in the analysis comparing the two treatment groups. We report the median and full range of these average changes for each group.

   A negative value indicates an improvement in symptoms.

3. Change From Baseline in Stuffy Nose Symptom Score Over 2 Week Randomized Treatment Period [ Time Frame: Baseline and 2 weeks ]

   Patients recorded the severity of stuffy nose twice a day on a scale from 0 to 3 (0 = no symptoms, 1 = mild, 2 = moderate, and 3 = severe). The stuffy nose symptom score was calculated as the sum of all scores for morning and evening recordings with a range of 0 to 6.

   The baseline symptom score used in the analysis was the average of the symptom scores from the last 5 days of fluticasone propionate therapy prior to randomized treatment period.

   The change from baseline for each subsequent day of treatment was then calculated for each subject. So that each subject only had one observation, the average of these changes was calculated for each subject, and this summary measure was used in the analysis comparing the two treatment groups. We report the median and full range of these average changes for each group.

   A negative value indicates an improvement in symptoms.

4. Change From Baseline in Other Symptom Score Over 2 Week Randomized Treatment Period [ Time Frame: Baseline and 2 weeks ]

   Patients recorded the severity of other symptoms, including itchy nose/eyes and post-nasal drip, twice a day on a scale from 0 to 3 (0 = no symptoms, 1 = mild, 2 = moderate, and 3 = severe). The other symptom score was calculated as the sum of all scores for morning and evening recordings with a range of 0 to 6.

   The baseline symptom score used in the analysis was the average of the symptom scores from the last 5 days of fluticasone propionate therapy prior to randomized treatment period.

   The change from baseline for each subsequent day of treatment was then calculated for each subject. So that each subject only had one observation, the average of these changes was calculated for each subject, and this summary measure was used in the analysis comparing the two treatment groups. We report the median and full range of these average changes for each group.

   A negative value indicates an improvement in symptoms.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 55 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

• A clinical history of perennial allergic rhinitis and a positive skin prick test to dust mite, cockroach, mold, or cat or dog antigens.
• Willingness of the subject to participate in and complete the study, and the ability to understand the purpose of the trial.

Exclusion Criteria:

• Physical signs or symptoms suggestive of renal, hepatic or cardiovascular disease.
• Women of childbearing potential who are pregnant, trying to become pregnant or nursing a child.
• Subjects treated with systemic steroids during the previous 30 days.
• Subjects treated with topical (inhaled, intranasal or intraocular) steroids, Nasalcrom or Opticrom during the previous 15 days.
• Subjects treated with oral antihistamines/decongestants during the previous seven days.
• Subjects treated with topical (intranasal or intraocular) antihistamines/decongestants during the previous 3 days.
• Subjects treated with immunotherapy who are escalating their dose.
• Subjects on chronic anti-asthma medications.
• Subjects with polyps in the nose or a significantly displaced septum.
• Subjects who have incurred an upper respiratory tract infection within 14 days of the start of the study.

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Illinois
The University of Chicago
Chicago, Illinois, United States, 60637

Sponsors and Collaborators

University of Chicago

Merck Sharp & Dohme Corp.

Investigators

Principal Investigator:	Robert M Naclerio, MD	University of Chicago

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications:

Wilson AM, White PS, Gardiner Q, Nassif R, Lipworth BJ. Effects of leukotriene receptor antagonist therapy in patients with chronic rhinosinusitis in a real life rhinology clinic setting. Rhinology. 2001 Sep;39(3):142-6.

Kurowski M, Kuna P, Górski P. Montelukast plus cetirizine in the prophylactic treatment of seasonal allergic rhinitis: influence on clinical symptoms and nasal allergic inflammation. Allergy. 2004 Mar;59(3):280-8.

van Adelsberg J, Philip G, Pedinoff AJ, Meltzer EO, Ratner PH, Menten J, Reiss TF; Montelukast Fall Rhinitis Study Group. Montelukast improves symptoms of seasonal allergic rhinitis over a 4-week treatment period. Allergy. 2003 Dec;58(12):1268-76. Erratum in: Allergy. 2004 Mar;59(3):357. Allergy. 2009 Nov;64(11):1697.

Philip G, Nayak AS, Berger WE, Leynadier F, Vrijens F, Dass SB, Reiss TF. The effect of montelukast on rhinitis symptoms in patients with asthma and seasonal allergic rhinitis. Curr Med Res Opin. 2004 Oct;20(10):1549-58.

Di Lorenzo G, Pacor ML, Pellitteri ME, Morici G, Di Gregoli A, Lo Bianco C, Ditta V, Martinelli N, Candore G, Mansueto P, Rini GB, Corrocher R, Caruso C. Randomized placebo-controlled trial comparing fluticasone aqueous nasal spray in mono-therapy, fluticasone plus cetirizine, fluticasone plus montelukast and cetirizine plus montelukast for seasonal allergic rhinitis. Clin Exp Allergy. 2004 Feb;34(2):259-67. Erratum in: Clin Exp Allergy. 2004 Aug;34(8):1329.

Ciprandi G, Tosca MA, Milanese M, Schenone G, Ricca V. Antihistamines added to an antileukotriene in treating seasonal allergic rhinitis: histamine and leukotriene antagonism. Eur Ann Allergy Clin Immunol. 2004 Feb;36(2):67-70, 72.

Chervinsky P, Philip G, Malice MP, Bardelas J, Nayak A, Marchal JL, van Adelsberg J, Bousquet J, Tozzi CA, Reiss TF. Montelukast for treating fall allergic rhinitis: effect of pollen exposure in 3 studies. Ann Allergy Asthma Immunol. 2004 Mar;92(3):367-73.

Moinuddin R, deTineo M, Maleckar B, Naclerio RM, Baroody FM. Comparison of the combinations of fexofenadine-pseudoephedrine and loratadine-montelukast in the treatment of seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2004 Jan;92(1):73-9.

Topuz B, Ogmen GG. Montelukast as an adjuvant to mainstay therapies in patients with seasonal allergic rhinitis. Clin Exp Allergy. 2003 Jun;33(6):823-6.

Ratner PH, Howland WC 3rd, Arastu R, Philpot EE, Klein KC, Baidoo CA, Faris MA, Rickard KA. Fluticasone propionate aqueous nasal spray provided significantly greater improvement in daytime and nighttime nasal symptoms of seasonal allergic rhinitis compared with montelukast. Ann Allergy Asthma Immunol. 2003 May;90(5):536-42.

Saengpanich S, deTineo M, Naclerio RM, Baroody FM. Fluticasone nasal spray and the combination of loratadine and montelukast in seasonal allergic rhinitis. Arch Otolaryngol Head Neck Surg. 2003 May;129(5):557-62.

Baena-Cagnani CE, Berger WE, DuBuske LM, Gurné SE, Stryszak P, Lorber R, Danzig M. Comparative effects of desloratadine versus montelukast on asthma symptoms and use of beta 2-agonists in patients with seasonal allergic rhinitis and asthma. Int Arch Allergy Immunol. 2003 Apr;130(4):307-13.

van Adelsberg J, Philip G, LaForce CF, Weinstein SF, Menten J, Malice MP, Reiss TF; Montelukast Spring Rhinitis Investigator Group. Randomized controlled trial evaluating the clinical benefit of montelukast for treating spring seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2003 Feb;90(2):214-22.

Philip G, Malmstrom K, Hampel FC, Weinstein SF, LaForce CF, Ratner PH, Malice MP, Reiss TF; Montelukast Spring Rhinitis Study Group. Montelukast for treating seasonal allergic rhinitis: a randomized, double-blind, placebo-controlled trial performed in the spring. Clin Exp Allergy. 2002 Jul;32(7):1020-8. Erratum in: Clin Exp Allergy. 2009 Oct;39(10):1622.

Nayak AS, Philip G, Lu S, Malice MP, Reiss TF; Montelukast Fall Rhinitis Investigator Group. Efficacy and tolerability of montelukast alone or in combination with loratadine in seasonal allergic rhinitis: a multicenter, randomized, double-blind, placebo-controlled trial performed in the fall. Ann Allergy Asthma Immunol. 2002 Jun;88(6):592-600.

Pullerits T, Praks L, Ristioja V, Lötvall J. Comparison of a nasal glucocorticoid, antileukotriene, and a combination of antileukotriene and antihistamine in the treatment of seasonal allergic rhinitis. J Allergy Clin Immunol. 2002 Jun;109(6):949-55.

Wilson AM, Sims EJ, Orr LC, Coutie WJ, White PS, Gardiner Q, Lipworth BJ. Effects of topical corticosteroid and combined mediator blockade on domiciliary and laboratory measurements of nasal function in seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2001 Oct;87(4):344-9.

Wilson AM, Dempsey OJ, Sims EJ, Lipworth BJ. A comparison of topical budesonide and oral montelukast in seasonal allergic rhinitis and asthma. Clin Exp Allergy. 2001 Apr;31(4):616-24.

Wilson AM, Orr LC, Sims EJ, Lipworth BJ. Effects of monotherapy with intra-nasal corticosteroid or combined oral histamine and leukotriene receptor antagonists in seasonal allergic rhinitis. Clin Exp Allergy. 2001 Jan;31(1):61-8.

Wilson AM, Orr LC, Sims EJ, Dempsey OJ, Lipworth BJ. Antiasthmatic effects of mediator blockade versus topical corticosteroids in allergic rhinitis and asthma. Am J Respir Crit Care Med. 2000 Oct;162(4 Pt 1):1297-301.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Esteitie R, deTineo M, Naclerio RM, Baroody FM. Effect of the addition of montelukast to fluticasone propionate for the treatment of perennial allergic rhinitis. Ann Allergy Asthma Immunol. 2010 Aug;105(2):155-61. doi: 10.1016/j.anai.2010.05.017. Epub 2010 Jun 19.

Responsible Party:	University of Chicago
ClinicalTrials.gov Identifier:	NCT00119015 History of Changes
Other Study ID Numbers:	13875B; SING-US-60-04
First Posted:	July 12, 2005
Results First Posted:	May 22, 2013
Last Update Posted:	February 28, 2014
Last Verified:	January 2014

Keywords provided by University of Chicago:

perennial allergic rhinitis

Additional relevant MeSH terms:

Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Nose Diseases; Respiratory Tract Diseases; Respiratory Tract Infections; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Fluticasone; Montelukast; Anti-Inflammatory Agents

Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Dermatologic Agents; Anti-Allergic Agents; Leukotriene Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Molecular Mechanisms of Pharmacological Action