Clinical trial NCT00509197
Conditions: Asthma
Keywords: Asthma Non-eosinophilic Asthma sputum eosinophils Inhaled Corticosteroids
Sponsor: Université de Montréal
Start date: 2007-10-01; Completion date: 2010-09-01
Enrollment: 12 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The efficacy of inhaled corticosteroids (ICS) in asthmatic subjects showing no sputum eosinophils is controversial. The broad aim of this study is to assess whether ICS alone or in combination with long-acting beta-2 agonists are an effective treatment in non-eosinophilic asthmatic subjects. Methods: The investigators will perform a randomized double-blind, placebo-controlled, multicenter study comparing the efficacy of ICS and placebo for 4 weeks followed by a 4-week open treatment period with ICS/salmeterol in steroid-naïve asthmatic subjects without sputum eosinophilia. The primary outcome will be the the Asthma Control Questionnaire (ACQ) score after four weeks of treatment by ICS or placebo.

This study will determine whether or not non-eosinophilic asthmatic subjects respond to ICS and if they further benefit from the addition of a long-acting beta-2 agonists. This study will also determine whether or not the assessment of airway inflammation should be performed in every asthmatic patient in order to give the most appropriate treatment.

Detailed description:
General objective: To assess whether inhaled corticosteroids alone or in combination with long-acting beta-2 agonists are an effective treatment in non-eosinophilic asthmatic subjects.

Specific objective 1. To compare the change in clinical and functional outcomes after treatment with fluticasone or placebo in non-eosinophilic asthmatic subjects.

Specific objective 2. To assess whether the combination of inhaled corticosteroids (ICS) and with long-acting beta-2 agonists provides an improvement of asthma control compared to the treatment with ICS or placebo in non-eosinophilic asthmatics.

Hypothesis: Treatment with ICS induces a significant clinical and physiologic improvement of non-eosinophilic asthmatic subjects. ICS/Salmeterol also provides a clinical and physiologic benefit compared to placebo.

Primary end point: Asthma Control Questionnaire (ACQ) score after 4 weeks of treatment with ICS or placebo.

The Asthma Control Questionnaire has been chosen as a primary outcome since it is the most relevant clinical measure to assess asthma control over a short period of time. In patients whose asthma is stable between clinic visits, reliability of the ACQ is high (intraclass correlation coefficient (ICC)=0.90). Furthermore, the questionnaire is also very responsive to changes in asthma control(7). Therefore, this is the ideal tool to assess and compare the changes in asthma control over a short period of time. This instrument has the advantage of including both asthma symptoms as well as forced expiratory flow in one second (FEV1). A change of ACQ of 0.5 has been shown to be clinically significant. Therefore, we will be able to assess whether or not a treatment with ICS has the ability to significantly improve asthma control in non-eosinophilic asthmatic subjects. The questionnaire is provided in appendix III. Other functional and clinical outcomes such as quality of life, FEV1, provocative concentration of methacholine inducing a 20% fall in FEV1 (PC20), number of rescue medication and number of asthma exacerbations will also be assessed as secondary outcomes.

The study has two steps: The first step will be a randomized double-blind, placebo-controlled, multicenter study comparing the efficacy of ICS and placebo for 4 weeks in asthmatic subjects without sputum eosinophilia followed by an open ICS/salmeterol 4-week treatment for all subjects. (See study design in appendix III).

Inclusion criteria One hundred subjects will be enrolled.

Arms: arm 1: Intervention : treatment with inhaled corticosteroids (Fluticasone) will be administered to this group arm 2: treatment with placebo
Interventions: intervention 1: Placebo (sham inhaler) intervention 2: Fluticasone
Intervention descriptions: intervention 1: None intervention 2: Fluticasone 250mcg bid for one month

Protocol documents: