Study to Investigate the Efficacy of Symbicort® SMART.

A Comparison of Symbicort® SMART (160/4.5μg) and Symbicort® Turbuhaler 160/4.5 μg, Plus Terbutaline Turbuhaler 0.4 mg as Needed, for Treatment of Asthma - a 12-month, Randomized, Double-blind, Parallel Group, Active-controlled, Multinational Phase III Study in Asthmatic Patients From 16 Years

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00839800

Acronym

SAKURA

Enrollment

2091

Registered

2009-02-10

Start date

2009-02-28

Completion date

2011-02-28

Last updated

2012-11-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Asthma

Keywords

Asthma, Symbicort Turbuhaler

Brief summary

The primary objective of this study is to compare the efficacy of Symbicort SMART (Symbicort Turbuhaler 160/4.5μg, one inhalation twice daily plus as needed) with Symbicort Turbuhaler 160/4.5μg, one inhalation twice daily plus terbutaline Turbuhaler 0.4 mg as needed, as asthma therapy

Interventions

DRUGSymbicort Turbuhaler

160/4.5 µg

DRUGTerbutaline Turbuhaler

0.4 mg

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

16 Years to No maximum

Healthy volunteers

Inclusion criteria

* Diagnosis of asthma according to the Global Initiative for Asthma guidelines (GINA) 2007 with a documented history of at least 6 months duration. * Reversible airway obstruction, defined as an increase in FEV1 ≥12% relative to baseline for all patients 15-30 minutes after inhalation of in total 2 x 0.4 mg terbutaline Turbuhaler * Prescribed use of inhaled glucocorticoid steroid (GCS) (any brand) for at least 12 weeks.

Exclusion criteria

* Respiratory infection affecting the asthma, as judged by the investigator, within 4 weeks. * Intake of oral, rectal or parenteral GCS within 4 weeks and/or depot parenteral GCS within 12 weeks.

Design outcomes

Primary

Measure	Time frame	Description
The Percentage of Participants Who Had Experienced Asthma Exacerbation(s) at the End of the Study	week 52	Asthma exacerbation was defined as deterioration in asthma leading to oral glucocorticosteroid \[GCS\] treatment, hospitalization, or emergency room \[ER\] treatment.

Secondary

Measure	Time frame	Description
Morning Peak Expiratory Flow (PEF)	52-week treatment period	The mean value from a 52-week treatment period.
Evening PEF	2-week run-in period (14 - 18 days before randomization - week 0) and a 52-week treatment period	The mean value from a 52-week treatment period.
Forced Expiratory Volume in One Second (FEV1)	4, 12, 24, 36 and 52 weeks after randomization	The mean value for Weeks 4, 12, 24, 36 and 52 was analysed.
Use of As-needed Medication	52-week treatment period	The mean value of total daily number of inhalations from the treatment period for use of as-needed medication (daytime, night-time).
Asthma Symptom Score	52-week treatment period	The mean value from the treatment period for Total Asthma Symptom Score (total score: 0 is best - no asthma symptoms; 6 is worst).
Number of Asthma Exacerbations	up to 52 weeks	Asthma exacerbation was defined as deterioration in asthma leading to oral GCS treatment, hospitalization, or ER treatment. Number of asthma exacerbations during 52 weeks treatment was presented here.
The Percentage of Participants Who Had Experienced First Mild Asthma Exacerbations	up to 52 weeks	Mild asthma exacerbation was defined as morning PEF ≥20% below baseline, daily as-needed medication use ≥2 inhalations above baseline, or a night with awakening due to asthma symptoms. The percentage of participants who had experienced mild asthma exacerbation(s) at the end of the study was presented here.
Symptom-free Days (no Symptoms and no Awakenings)	52-week treatment period	A symptom-free day was defined as a day without daytime or night-time symptoms and without night-time awakenings due to asthma symptoms. The mean value was presented here.
Percentage of As-needed-free Days	52-week treatment period	An as-needed-free day is defined as a night and day with no use of as-needed medication. The mean value from the treatment period was presented here.
Percentage of Asthma-control Days (no Asthma Symptoms, no Awakenings, and no As-needed Use)	52-week treatment period	An asthma-control day was defined as a a night and day with no asthma symptoms, no awakenings due to asthma symptoms, and no as-needed medication use. The mean value from the treatment period was presented here.
Asthma Control Questionnaire (ACQ)	4, 12, 24, 36 and 52 weeks after randomization	The ACQ developed by Juniper and colleagues (Juniper et al 1999) was used without the FEV1 and Beta 2-agonist questions. The Asthma Control Questionnaire has 5 questions that are assessed on a 7-point scale from 0 to 6 where 0 represents good control and 6 represents poor control. The overall score is the mean of the five responses. At least 4 out of the 5 questions must have been answered to provide a value. The mean of the overall score for Weeks 4 to 52 was presented here.
Nights With Awakening(s) Due to Asthma Symptoms	52-week treatment period	The mean value from the treatment period was presented here.

Countries

Argentina, Brazil, China, Costa Rica, Hungary, India, Japan, Malaysia, Peru, Philippines, South Korea, Thailand

Participant flow

Recruitment details

The first participant entered the study on 16 February 2009, and the last participant completed the study on 23 February 2011. A total of 3209 participants were enrolled at 148 centres in 13 countries in Asia, America and Europe, and 2091 participants who fulfilled the randomisation criteria were randomised.

Pre-assignment details

The study started with an enrolment visit, Visit 1, 1-7 days prior to Visit 2 (run-in). At Visit 2 patients had to have a reversibility of ≥12% relative to baseline and their pre-bronchodilatory Forced expiratory volume in one second (FEV1) had to be ≥50% of the predicted normal value.

Participants by arm

Arm	Count
Symbicort SMART Symbicort Turbuhaler 160/4.5 microgram (mcg) one inhalation twice daily (bid) + Symbicort Turbuhaler 160/4.5 mcg as needed	1,049
Symbicort+Terbutaline As Needed Symbicort Turbuhaler 160/4.5 mcg one inhalation twice daily + terbutaline Turbuhaler 0.4 mg as needed	1,042
Total	2,091

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	8	12
Overall Study	Incorrect Enrolment	3	3
Overall Study	Lost to Follow-up	31	26
Overall Study	Other	8	14
Overall Study	Safety Reasons	2	1
Overall Study	Severe Non-Compliance to Protocol	7	7
Overall Study	Study-Specific Discontinuation Criteria	6	13
Overall Study	Withdrawal by Subject	28	34

Baseline characteristics

Characteristic	Symbicort SMART	Symbicort+Terbutaline As Needed	Total
Age Continuous	45.7 years	45.6 years	45.7 years
Sex: Female, Male Female	722 Participants	692 Participants	1414 Participants
Sex: Female, Male Male	327 Participants	350 Participants	677 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	279 / 1,049	293 / 1,042
serious Total, serious adverse events	41 / 1,049	74 / 1,042

Outcome results

Primary

The Percentage of Participants Who Had Experienced Asthma Exacerbation(s) at the End of the Study

Asthma exacerbation was defined as deterioration in asthma leading to oral glucocorticosteroid \[GCS\] treatment, hospitalization, or emergency room \[ER\] treatment.

Time frame: week 52