Efficacy and Safety of add-on Montelukast to Inhaled Budesonide in the Treatment of Nonasthmatic Eosinophilic Bronchitis (NAEB)

Randomized Double-blind Placebo-controlled Study of add-on Montelukast to Inhaled Budesonide in the Treatment of Nonasthmatic Eosinophilic Bronchitis

Hypothesis: Add-on therapy with oral montelukast (Mon) to inhaled budesonide (BUD) may achieve better control of cough caused by nonasthmatic eosinophilic bronchitis (NAEB) with faster reduction of airway eosinophilia.

Objective: To evaluate the efficacy of add-on therapy with Mon to inhaled corticosteroids (ICS) in the treatment of adult patients with chronic/subacute cough caused by NAEB diagnosed in outpatient setting. Primary endpoint：cough severity rated as cough visual analogue score (VAS)1 and eosinophil count in induced sputum during 4-week BUD monotherapy or Mon adjunct therapy.

Study Overview

• Status: Unknown
• Conditions: Nonasthmatic Eosinophilic Bronchitis
• Intervention / Treatment: Drug: Montelukast; Other: placebo to montelukast

Detailed Description

Subjects：63 newly-diagnosed, steroid-naïve adult patients with chronic or subacute cough caused by NAEB.

Grouping：ICS monotherapy (21 patients, BUD，400mcg mcg, twice daily+ placebo, 4 wks); Mon adjunct therapy (42 patients, Mon 10mg once daily + BUD 400mcg twice daily 4wks).

Protocol Day 1: In the respiratory specialist clinic, the diagnosis of NAEB is established following the 2006 ACCP guideline (sputum eosinophilia >3%, negative chest radiography, spirometry and bronchial provocation test). After briefing, eligible subjects who have given informed written consents, are to be randomly allocated to different treatment groups. Patients' demographical data, course and nature of cough, accompanying symptoms and upper respiratory comorbidities, skin prick test to common aeroallergens1, baseline cough VAS (0-100 mm) 1, spirometry and induced sputum cell counts, will be recorded by the managing physician in case record file (CRF). Pulmicort Turbuhaler (AstraZeneca, budesonide 100 mcg/dose X 200 doses) will be prescribed to each patient.

Day 2: Before initiation of treatment, at the Office for Clinical Trials, staff members will instruct the patients on correct usage of ICS, disperse Mon tablets or placebo as well as daily record cards, and explain how to record daily use of ICS and Mon, and adverse events. Once the treatment is initiated, oral steroids, other ICS, anti-histamines, beta-2 agonists and theophyllines will not be prescribed and used throughout the study period.

Day 8、15：Revisits: Patients' nature of cough, accompanying symptoms, cough VAS, induced sputum cell count will be reevaluated and recorded in CRF. Old daily record cards will be collected. New ones as well as Mon tablets or placebo will be given. Patients' skill of using ICS, compliance, systemic or local adverse events will be monitored.

Day 29： Revisit: Patients' nature of cough, accompanying symptoms, cough VAS, spirometry, bronchial provocation test, induced sputum cell count will be reevaluated and recorded in CRF. Old daily record cards will be collected. Patients' skill of using ICS, compliance, systemic or local adverse events will be recorded.

• Study Type: Interventional
• Enrollment (Anticipated): 63
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Guangzhou Institute of Respiratory Disease

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult nonsmoking NAEB patients
• Without history of taking Mon, oral or inhaled corticosteroids, and
• Without bacterial or viral respiratory infections within 30 days prior to diagnosis of NAEB

Exclusion Criteria:

• Current smokers
• Pregnant or lactating women
• Known allergy to Mon, oral or inhaled corticosteroids
• Unable to use ICS following repeated instructions
• Complicated with unresectable malignancy or severe heart, lung, liver or kidney diseases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: combination therapy; combination therapy with inhaled budesonide and oral montelukast	Drug: Montelukast; 10mg, qn, 4 weeks; Other Names: Singulair
Placebo Comparator: monotherapy; monotherapy with inhaled budesonide and placebo of montelukast	Other: placebo to montelukast; same appearance, flavor, weight, and size to montelukast pills, 1 pill daily, for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
cough severity rated as cough visual analogue score (VAS)	4 weeks
eosinophil count in induced sputum	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse reactions	any discomforts or untoward events observed during the study period	4 weeks

Collaborators and Investigators

• Sponsor: Guangzhou Medical University

Publications and helpful links

General Publications

• Birring SS, Berry M, Brightling CE, Pavord ID. Eosinophilic bronchitis: clinical features, management and pathogenesis. Am J Respir Med. 2003;2(2):169-73. doi: 10.1007/BF03256647.
• Cai C, He MZ, Zhong SQ, Tang Y, Sun BQ, Chen QL, Zhong NS. Add-on montelukast vs double-dose budesonide in nonasthmatic eosinophilic bronchitis: a pilot study. Respir Med. 2012 Oct;106(10):1369-75. doi: 10.1016/j.rmed.2012.06.009. Epub 2012 Jul 21.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Anticipated): June 1, 2011
• Study Completion (Anticipated): June 1, 2011

Study Registration Dates

• First Submitted: May 11, 2010
• First Submitted That Met QC Criteria: May 11, 2010
• First Posted (Estimate): May 12, 2010

Study Record Updates

• Last Update Posted (Estimate): May 12, 2010
• Last Update Submitted That Met QC Criteria: May 11, 2010
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Keywords: NAEB, chronic cough, montelukast, induced sputum
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Bronchial Diseases; Lung Diseases, Obstructive; Acute Disease; Bronchitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Asthmatic Agents; Respiratory System Agents; Leukotriene Antagonists; Hormone Antagonists; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Montelukast
• Other Study ID Numbers: moneb