Should Non-eosinophilic Asthmatic Subjects be Treated With Inhaled Corticosteroids?

• Sponsor: Université de Montréal (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00509197
• Collaborator: University of Ottawa (Other), Laval University (Other), University of British Columbia (Other), McGill University (Other), University of Calgary (Other)
• Enrollment: 12
• Locations: 7
• Arms: 2
• Duration (Months): 35
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Placebo (sham inhaler); Drug: Fluticasone	N/A

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

1. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Should Non-eosinophilic Asthmatic Subjects be Treated With Inhaled Corticosteroids?
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Active treatment group (A) Intervention : treatment with inhaled corticosteroids (Fluticasone) will be administered to this group	Drug: Fluticasone; Fluticasone 250mcg bid for one month; Other Names: Flovent
Placebo Comparator: Control group treated with placebo (B) treatment with placebo	Drug: Placebo (sham inhaler); Other Names: Sham inhaler

Outcome Measures

Primary Outcome Measures

1. Asthma Control Questionnaire (ACQ) Score After 4 Weeks of Treatment With Inhaled Corticosteroids (ICS) or Placebo [Four weeks]

   Validated questionnaire assessing asthma control after 4 weeks of treatment with ICS or placebo. The ACQ has 7 questions (the top scoring 5 symptoms, FEV1% pred. and daily rescue bronchodilator use). Patients are asked to recall how their asthma has been during the previous week and to respond to the symptom and bronchodilator use questions on a 7-point scale (0=no impairment, 6= maximum impairment). The ACQ score is the mean of 7 items and thus ranges between 0 (well controlled) and 6 (extremely poorly controlled) to yield a mean score out of 6. The higher the score, the worst asthma control is.

Secondary Outcome Measures

1. Asthma Quality of Life Questionnaire (AQLQ) Score After 4 Weeks of Treatment [Four weeks]

   Validated questionnaire assessing quality of life related to asthma after 4 weeks of treatment. The AQLQ is composed of 32 questions in 4 domains (symptoms, activity limitation, emotional function and environmental stimuli). The activity domain contains 5 'patient-specific' questions. This allows patients to select 5 activities in which they are most limited and these activities will be assessed at each follow-up. Patients are asked to think about how they have been during the previous two weeks and to respond to each of the 32 questions on a 7-point scale (7 = not impaired at all - 1 = severely impaired). The AQLQ score is rated on a 7-point scale (1=maximal impairment, 7=no impairment) to yield a mean score out of 7. The worse the quality of life is , the lower the score is.

2. Change in Forced Expiratory Volume in One Second (FEV1) [Four weeks]

   Change in forced expiratory volume in one second (FEV1) after fluticasone or placebo treatment.

3. Change in Provocative Concentration of Methacholine Inducing a 20% Fall in FEV1 (PC20) [Four weeks]

   Change in provocative concentration of methacholine inducing a 20% fall in FEV1 (PC20) after fluticasone or placebo treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Are between 18 and 70 years of age at the time of signing the informed consent.

• Have a diagnosis of asthma according to the Guidelines for the Diagnosis and Management of Asthma and have not been treated with ICS in the previous two months.

• Have a PC20 methacholine less than 8 mg/ml.

• Have a baseline FEV1 greater or equal to 65% of predicted value (at least 6 hours after bronchodilator).

• Are not optimally controlled with short-acting 2 agonists as shown by awakenings due to asthmatic symptoms at least once a week, or regular use of salbutamol on 4 or more occasions per week (excluding exercise prophylaxis) due to asthma symptoms.

• ACQ score equal or greater than 2

• Have sputum eosinophils less than 2%

• Are non smokers or ex-smokers who smoked a maximum of 10 pack/year.

Exclusion Criteria:

• Hospitalized patients within the last 3 months

• Current or recent (within the last month) symptoms of a cold or flu

• Patients with a history of near fatal asthma

• Subjects on inhaled corticosteroids, prednisone, long-acting beta 2 agonists, montelukast or theophylline, within 2 months prior to entry into the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Calgary University	Calgary	Alberta	Canada
2	Vancouver General Hospital	Vancouver	British Columbia	Canada	V5Z 1M9
3	Firestone Institute for Respiratory Health	Hamilton	Ontario	Canada
4	The Ottawa Hospital	Ottawa	Ontario	Canada	K1H 8L6
5	The Meakins-Christie Laboratories	Montreal	Quebec	Canada	H2X 2P2
6	Hôpital du Sacré-Coeur de Montréal	Montréal	Quebec	Canada	H4J 1C5
7	Hôpital Laval	Quebec		Canada	G1V 4G5

Sponsors and Collaborators

• Université de Montréal
• University of Ottawa
• Laval University
• University of British Columbia
• McGill University
• University of Calgary

Investigators

• Principal Investigator: Catherine Lemiere, MD,MSc, Hopital du Sacre-Coeur de Montreal

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Catherine Lemiere, MD,MSc, Université de Montréal
• ClinicalTrials.gov Identifier: NCT00509197
• Other Study ID Numbers: SFA110717
• First Posted: Jul 31, 2007
• Last Update Posted: Aug 15, 2016
• Last Verified: Jul 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Catherine Lemiere, MD,MSc, Université de Montréal: Asthma; Non-eosinophilic Asthma; sputum eosinophils; Inhaled Corticosteroids
• Additional relevant MeSH terms: Asthma; Fluticasone

Study Results

Participant Flow

Arm/Group Title	Fluticasone 500 mcg Bid	Placebo
Arm/Group Description	Treatment with Inhaled Corticosteroids	treatment with placebo
Period Title: Overall Study
STARTED	6	6
COMPLETED	6	6
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Fluticasone 500 mcg Bid	Placebo	Total
Arm/Group Description	Treatment with inhaled corticosteroids	Treatment with placebo	Total of all reporting groups
Overall Participants	6	6	12
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	6 100%	6 100%	12 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38 (15.3)	43 (11.7)	40.5 (13.2)
Sex: Female, Male (Count of Participants)
Female	5 83.3%	2 33.3%	7 58.3%
Male	1 16.7%	4 66.7%	5 41.7%
Region of Enrollment (participants) [Number]
Canada	6 100%	6 100%	12 100%

Outcome Measures

1. Primary Outcome

Title	Asthma Control Questionnaire (ACQ) Score After 4 Weeks of Treatment With Inhaled Corticosteroids (ICS) or Placebo
Description	Validated questionnaire assessing asthma control after 4 weeks of treatment with ICS or placebo. The ACQ has 7 questions (the top scoring 5 symptoms, FEV1% pred. and daily rescue bronchodilator use). Patients are asked to recall how their asthma has been during the previous week and to respond to the symptom and bronchodilator use questions on a 7-point scale (0=no impairment, 6= maximum impairment). The ACQ score is the mean of 7 items and thus ranges between 0 (well controlled) and 6 (extremely poorly controlled) to yield a mean score out of 6. The higher the score, the worst asthma control is.
Time Frame	Four weeks

Outcome Measure Data

Analysis Population Description

Intention to treat

Arm/Group Title	Fluticasone	Placebo
Arm/Group Description	Treatment with inhaled corticosteroids	Use of placebo inhaler (sham fluticasone)
Measure Participants	6	6
Mean (Standard Deviation) [units on a scale]	1.4 (0.5)	2.2 (0.7)

2. Secondary Outcome

Title	Asthma Quality of Life Questionnaire (AQLQ) Score After 4 Weeks of Treatment
Description	Validated questionnaire assessing quality of life related to asthma after 4 weeks of treatment. The AQLQ is composed of 32 questions in 4 domains (symptoms, activity limitation, emotional function and environmental stimuli). The activity domain contains 5 'patient-specific' questions. This allows patients to select 5 activities in which they are most limited and these activities will be assessed at each follow-up. Patients are asked to think about how they have been during the previous two weeks and to respond to each of the 32 questions on a 7-point scale (7 = not impaired at all - 1 = severely impaired). The AQLQ score is rated on a 7-point scale (1=maximal impairment, 7=no impairment) to yield a mean score out of 7. The worse the quality of life is , the lower the score is.
Time Frame	Four weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fluticasone	Placebo
Arm/Group Description	Treatment with inhaled corticosteroids	Use of placebo inhaler (sham fluticasone)
Measure Participants	6	6
Mean (Standard Deviation) [units on a scale]	5.5 (1.2)	4.8 (1.1)

3. Secondary Outcome

Title	Change in Forced Expiratory Volume in One Second (FEV1)
Description	Change in forced expiratory volume in one second (FEV1) after fluticasone or placebo treatment.
Time Frame	Four weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fluticasone	Placebo
Arm/Group Description	Treatment with Fluticasone	Treatment with placebo
Measure Participants	6	6
Mean (Standard Deviation) [L]	0.04 (0.1)	-0.2 (0.2)

4. Secondary Outcome

Title	Change in Provocative Concentration of Methacholine Inducing a 20% Fall in FEV1 (PC20)
Description	Change in provocative concentration of methacholine inducing a 20% fall in FEV1 (PC20) after fluticasone or placebo treatment
Time Frame	Four weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fluticasone	Placebo
Arm/Group Description	Treatment with inhaled corticosteroids	Use of placebo inhaler (sham fluticasone)
Measure Participants	6	6
Mean (Standard Deviation) [mg/ml]	3.4 (0.6)	2.1 (2.6)

Adverse Events

Arm/Group Title	Fluticasone 500 mcg Bid		Placebo
Arm/Group Description	Treatment with inhaled Corticosteroids		Treatment with placebo
All Cause Mortality
	Fluticasone 500 mcg Bid		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Fluticasone 500 mcg Bid		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Fluticasone 500 mcg Bid		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)

Limitations/Caveats

Very small sample size. Impossible to recruit the anticipated number of subjects.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.