Symbicort Single Inhaler Therapy vs conventional best practice for the treatment of persistent asthma in adults

Study identifier:D5890L00010

ClinicalTrials.gov identifier:N/A

EudraCT identifier:2005-005974-64

CTIS identifier:N/A

Terminated/Withdrawn

Official Title

A comparison of Symbicort Single Inhaler Therapy (Symbicort Turbuhaler 160/4.5 micrograms, 1 inhalation b.i.d. plus as needed) and conventional best practice for the treatment of persistent asthma in adults - a 26-week, randomised, open-label, parallel-group, multicentre study. Study SPAIN

Medical condition

ASTHMA, BRONCHIAL

Phase

Phase 3

Healthy volunteers

Study drug

Symbicort (budesonide/formoterol) Turbuhaler, Conventional treatment

Sex

All

Actual Enrollment

654

Study type

Interventional

Age

18 Years +

Date

Study Start Date: 01 Sept 2006

Primary Completion Date: -

Study Completion Date: 01 Oct 2008

Study design

Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Nov 2010 by AstraZeneca Pharmaceuticals

Collaborators

Inclusion and exclusion criteria

Location

Research Site

A Coruna, Spain

Location

Research Site

Alagon, Spain

Location

Research Site

Alicante, Spain

Location

Research Site

Almoradi, Spain

Location

Research Site

Barcelona, Spain

Location

Research Site

Burgos, Spain

Location

Research Site

Cadiz, Spain

Location

Research Site

Caravaca, Spain

Arms	Assigned Interventions

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
654

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
SMART	Symbicort Turbuhaler 160/4.5μg, 1 inhalation b.i.d. + as needed (in response to symptoms)
Conv. Best Practice	Conventional best practice, active stepwise individualized treatment according to international asthma treatment guidelines (GINA guidelines)); stepwise treatment according to the investigator’s clinical judgement.

Participant Flow: Overall Study

	SMART	Conv. Best Practice
STARTED	328	326
COMPLETED	270	289
NOT COMPLETED	58	37
Adverse Event	3	2
Withdrawal by Subject	17	7
Lost to Follow-up	12	8
Protocol Violation	7	4
Several reasons	17	15
Incorrect inclusion	2	0
Incorrect randomization	0	1

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
SMART	Symbicort Turbuhaler 160/4.5μg, 1 inhalation b.i.d. + as needed (in response to symptoms)
Conv. Best Practice	Conventional best practice, active stepwise individualized treatment according to international asthma treatment guidelines (GINA guidelines)); stepwise treatment according to the investigator’s clinical judgement.

Baseline Measures

	SMART	Conv. Best Practice	Total
Number of Participants [units: Participants]	328	326	654
Age Continuous [units: Years] Mean ± Standard Deviation	43.7 ± 16.4	44.3 ± 16.5	44.0 ± 16.5
Gender, Male/Female [units: Participants]
Female	218	202	420
Male	110	124	234

Outcome Measures

1. Primary Outcome Measure: Time to first severe asthma exacerbation [ Time Frame: Baseline up to 6 months ]

Measure Type	Primary
Measure Name	Time to first severe asthma exacerbation
Measure Description	Severe asthma exacerbation is defined as deterioration in asthma leading to at least one of Hospitalization/Emergency room (or equivalent) treatment due to asthma or Oral Glucocorticosteroids (GCS) treatment for at least 3 days.
Time Frame	Baseline up to 6 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
SMART	Symbicort Turbuhaler 160/4.5μg, 1 inhalation b.i.d. + as needed (in response to symptoms)
Conv. Best Practice	Conventional best practice, active stepwise individualized treatment according to international asthma treatment guidelines (GINA guidelines)); stepwise treatment according to the investigator’s clinical judgement.

Measured Values

	SMART	Conv. Best Practice
Number of Participants Analyzed [units:participants]	328	326
Time to first severe asthma exacerbation [units: Days] Mean (Standard Deviation)	174.39 (1.76)	178.97 (1.86)

No statistical analysis provided for Time to first severe asthma exacerbation

2. Secondary Outcome Measure: Total number of severe exacerbations [ Time Frame: Baseline up to 6 months ]

Measure Type	Secondary
Measure Name	Total number of severe exacerbations
Measure Description	Severe asthma exacerbation is defined as deterioration in asthma leading to at least one of Hospitalization/Emergency room (or equivalent) treatment due to asthma or Oral (GCS) treatment for at least 3 days.
Time Frame	Baseline up to 6 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
SMART	Symbicort Turbuhaler 160/4.5μg, 1 inhalation b.i.d. + as needed (in response to symptoms)
Conv. Best Practice	Conventional best practice, active stepwise individualized treatment according to international asthma treatment guidelines (GINA guidelines)); stepwise treatment according to the investigator’s clinical judgement.

Measured Values

	SMART	Conv. Best Practice
Number of Participants Analyzed [units:participants]	328	326
Total number of severe exacerbations [units: Exacerbations]	24	34

No statistical analysis provided for Total number of severe exacerbations

3. Secondary Outcome Measure: Mean use of as needed medication [ Time Frame: Baseline up to 6 months ]

Measure Type	Secondary
Measure Name	Mean use of as needed medication
Measure Description	Mean use of as needed medication during the treatment period
Time Frame	Baseline up to 6 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
SMART	Symbicort Turbuhaler 160/4.5μg, 1 inhalation b.i.d. + as needed (in response to symptoms)
Conv. Best Practice	Conventional best practice, active stepwise individualized treatment according to international asthma treatment guidelines (GINA guidelines)); stepwise treatment according to the investigator’s clinical judgement.

Measured Values

	SMART	Conv. Best Practice
Number of Participants Analyzed [units:participants]	308	320
Mean use of as needed medication [units: Inhalations] Mean (Full Range)	1.03 (0 to 6)	1.02 (0 to 9)

No statistical analysis provided for Mean use of as needed medication

4. Secondary Outcome Measure: Use of inhaled steroids [ Time Frame: Baseline up to 6 months ]

Measure Type	Secondary
Measure Name	Use of inhaled steroids
Measure Description	Mean micrograms/day of inhaled steroids (beclomethasone dipropionate equivalents)
Time Frame	Baseline up to 6 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
SMART	Symbicort Turbuhaler 160/4.5μg, 1 inhalation b.i.d. + as needed (in response to symptoms)
Conv. Best Practice	Conventional best practice, active stepwise individualized treatment according to international asthma treatment guidelines (GINA guidelines)); stepwise treatment according to the investigator’s clinical judgement.

Measured Values

	SMART	Conv. Best Practice
Number of Participants Analyzed [units:participants]	328	326
Use of inhaled steroids [units: micrograms] Mean (Full Range)	799 (250 to 2000)	1184 (200 to 4000)

No statistical analysis provided for Use of inhaled steroids

5. Secondary Outcome Measure: Change in the Asthma Control Questionnaire(ACQ) score [ Time Frame: Daily 14 days prior to each of visit 2-4 ]

Measure Type	Secondary
Measure Name	Change in the Asthma Control Questionnaire(ACQ) score
Measure Description	The ACQ is a 7-point scale with scores ranging from 0 (very well controlled) to 6 (very badly controlled)
Time Frame	Daily 14 days prior to each of visit 2-4
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
SMART	Symbicort Turbuhaler 160/4.5μg, 1 inhalation b.i.d. + as needed (in response to symptoms)
Conv. Best Practice	Conventional best practice, active stepwise individualized treatment according to international asthma treatment guidelines (GINA guidelines)); stepwise treatment according to the investigator’s clinical judgement.

Measured Values

	SMART	Conv. Best Practice
Number of Participants Analyzed [units:participants]	301	306
Change in the Asthma Control Questionnaire(ACQ) score [units: Scores on a scale] Mean (Full Range)	0.99 (0 to 4)	1.08 (0 to 3.4)

No statistical analysis provided for Change in the Asthma Control Questionnaire(ACQ) score

6. Secondary Outcome Measure: Peak Expiratory Flow (PEF) [ Time Frame: 6 months (end of the study) ]

Measure Type	Secondary
Measure Name	Peak Expiratory Flow (PEF)
Measure Description	Peak expiratory flow (PEF)
Time Frame	6 months (end of the study)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
SMART	Symbicort Turbuhaler 160/4.5μg, 1 inhalation b.i.d. + as needed (in response to symptoms)
Conv. Best Practice	Conventional best practice, active stepwise individualized treatment according to international asthma treatment guidelines (GINA guidelines)); stepwise treatment according to the investigator’s clinical judgement.

Measured Values

	SMART	Conv. Best Practice
Number of Participants Analyzed [units:participants]	285	299
Peak Expiratory Flow (PEF) [units: L/min] Mean (Full Range)	405.9 (110 to 900)	400.6 (140 to 900)

No statistical analysis provided for Peak Expiratory Flow (PEF)

Serious Adverse Events

Time Frame	No text entered.
Additional Description	The safety analysis set included 652 patients, because two patients in the Symbicort SMART arm were excluded from the safety analysis because they didn’t take any dose of medication

Reporting Groups

	Description
SMART	Symbicort Turbuhaler 160/4.5μg, 1 inhalation b.i.d. + as needed (in response to symptoms)
Conv. Best Practice	Conventional best practice, active stepwise individualized treatment according to international asthma treatment guidelines (GINA guidelines)); stepwise treatment according to the investigator’s clinical judgement.