Small Particle Steroids in Refractory Asthma (SPIRA)

Small Particle Inhaled Steroids in Refractory Steroid-responsive Asthma

The purpose of this study is to determine whether an inhaled steroid with a small particle size can be an additional treatment option in patients with refractory eosinophilic asthma.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Ciclesonide; Drug: Placebo

Detailed Description

We have identified a group of patients with refractory asthma who have ongoing eosinophilic airway inflammation despite high dose inhaled corticosteroids.

Traditional inhaled steroids have a relatively proximal airway distribution which may lead to inadequate treatment of the distal airways.

We aim to demonstrate that a steroid inhaler with a smaller particle size which targets the distal airways can be a useful additional treatment option in this group of patients.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE3 9QP
      • University Hospitals Of Leicester Nhs Trust
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
      • Nottingham University Hospitals NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18-80
• ACQ >1.5 or a requirement for oral steroids twice a year or more
• High dose inhaled steroid (>1000mcg BDP or equivalent)

• Treatment with or unsuccessful trial of:

  • long-acting beta agonist
  • leukotriene antagonist
• Sputum eosinophil count >3% despite high dose inhaled steroid or >2% with serum eosinophils >0.4x10exp9/l

• Clinical response to 2 weeks of oral prednisolone: (any one)

  • reduction in ACQ by 0.5 or more
  • increase in FEV1 by 200ml
  • normalisation of exhaled nitric oxide or reduction of >25ppb

Exclusion Criteria:

• Current smoker, or ex-smoker for <12 months
• Current treatment with an extrafine steroid inhaler
• Respiratory infection within the last 4 weeks
• Pregnancy or lactation
• Poor compliance with usual asthma medication
• Clinical diagnosis of significant bronchiectasis

• Use of a medication which may interact with ciclesonide:

  • ketoconazole or itraconazole
  • ritonavir, nelfinavir

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ciclesonide; Ciclesonide 320 microgrammes twice daily	Drug: Ciclesonide; Inhaled ciclesonide 320mcg twice daily; Other Names: Alvesco
Placebo Comparator: Placebo; Placebo 2 inhalations twice daily	Drug: Placebo; Matched placebo inhaler two inhalations twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in sputum eosinophil count over the trial period	Sputum will be processed for a differential cell count, with the primary outcome the difference in sputum eosinophil count between active and placebo groups at 8 weeks	0 weeks (start), 8 weeks (finish)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in alveolar nitric oxide level over the trial period	alveolar nitric oxide has been shown to correlate with eosinophil count on BAL samples. Measured by measuring exhaled nitric oxide at multiple flow rates.	0 weeks (start), 4 weeks, 8 weeks (finish)
Change in bronchial nitric oxide level	Measured by single flow exhaled nitric oxide at 50 ml/s	0 weeks (start), 4 weeks, 8 weeks (finish)
Change in prebronchodilator FEV1	Prebronchodilator FEV1 and FVC will be recorded with a Vitalograph Wedge Bellows spirometer	0 weeks (start), 4 weeks, 8 weeks (finish)
Change in Juniper Asthma Control Questionnaire (ACQ) score	UK English Version 2001	0 weeks (start), 4 weeks, 8 weeks (finish)
Change in Juniper Asthma Quality of Life Questionnaire (AQLQ) score	Self-administered United Kingdom Version 1994	0 weeks (start), 4 weeks, 8 weeks (finish)
Use of oral steroid over the trial period	Dose and duration of any additional oral corticosteroid will be documented	0-8 weeks
Number of patients with adverse events as a measure of safety and tolerability	Adverse events will be recorded throughout the trial period	0-8 weeks

Collaborators and Investigators

• Sponsor: University of Nottingham
• Collaborators: Nottingham University Hospitals NHS Trust; University Hospitals, Leicester
• Investigators: Principal Investigator: Tim Harrison, University of Nottingham; Principal Investigator: Ian Pavord, University Hospitals, Leicester

Publications and helpful links

General Publications

• Hodgson D, Anderson J, Reynolds C, Meakin G, Bailey H, Pavord I, Shaw D, Harrison T. A randomised controlled trial of small particle inhaled steroids in refractory eosinophilic asthma (SPIRA). Thorax. 2015 Jun;70(6):559-65. doi: 10.1136/thoraxjnl-2014-206481. Epub 2015 Apr 9.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: June 24, 2010
• First Submitted That Met QC Criteria: July 27, 2010
• First Posted (Estimate): July 28, 2010

Study Record Updates

• Last Update Posted (Estimate): January 31, 2014
• Last Update Submitted That Met QC Criteria: January 30, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Asthma; Respiratory Tract Diseases; Lung Diseases; Ciclesonide; Therapeutic Uses; Nitric Oxide; Pulmonary Eosinophilia
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Allergic Agents; Ciclesonide
• Other Study ID Numbers: 09115