Clinical trial NCT02149199: A Clinical Study to Evaluate Symbicort Turbuhaler Used 'as Needed' in Adults and Adolescents With Asthma.
Official title: A Clinical Study Comparing Symbicort® 'as Needed' With Terbutaline 'as Needed' and With Pulmicort® Twice Daily Plus Terbutaline 'as Needed' in Adult and Adolescent Patients With Asthma.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2014-05-29
Enrollment: 3850
Sex: ALL
Minimum age (years): 12
Maximum age (years): 130
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to test if Symbicort® (budesonide/formoterol) Turbuhaler® is effective in treating asthma when used 'as needed' in patients with milder asthma. The efficacy of Symbicort® 'as needed' will be compared with: 1) terbutaline Turbuhaler® 'as needed' and with 2) Pulmicort (budesonide) Turbuhaler® twice daily plus terbutaline Turbuhaler® 'as needed'.

Detailed description: A 52-week, double-blind, randomised, multi-centre, parallel-group, Phase III study in patients 12 years and older with asthma, evaluating the efficacy and safety of Symbicort® (budesonide/formoterol) Turbuhaler® 160/4.5 μg 'as needed' compared with terbutaline Turbuhaler® 0.4 mg 'as needed' and with Pulmicort® (budesonide) Turbuhaler® 200 μg twice daily plus terbutaline Turbuhaler® 0.4 mg 'as needed'

Eligibility criteria: INCLUSION CRITERIA 1. Provision of informed consent prior to any study specific procedures. For patients under-age, signed informed consent from both the patient and the patient's parent/legal guardian is required 2. Male or Female, ≥12 years of age 3. Documented diagnosis of asthma for at least 6 months prior to Visit 1 4. Patients who are in need of Step 2 treatment according to Global Initiative for Asthma guidelines 5. Patients treated with 'as needed' inhaled short-acting bronchodilator(s) only should have pre-bronchodilator Forced Expiratory Volume in one second (FEV1) ≥ 60 % of Predicted Normal (PN) and post-bronchodilator FEV1 ≥ 80 % PN 6. Patients treated with low stable dose of inhaled corticosteroid or leukotriene antagonist in addition to 'as needed' use of inhaled short-acting bronchodilator(s) should have pre-bronchodilator FEV1 ≥80 % PN 7. Patients should have reversible airway obstruction 8. To be randomized patients must have used Bricanyl Turbuhaler 'as needed' on at least 3 separate days during the last week of the run in period. EXCLUSION CRITERIA 1. Patient has a history of life-threatening asthma including intubation and intensive care unit admission 2. Patient has had an asthma worsening requiring change in treatment other than inhaled short-acting bronchodilator(s) within 30 days prior to Visit 1 or between Visits 1 and 2; or a treatment other than Bricanyl Turbuhaler from Visit 2 until randomization 3. Patient has required treatment with oral, rectal or parenteral glucocorticosteroids (GCS) within 30 days and/or depot parenteral GCS within 12 weeks prior to Visit 1 4. Smoker (current or previous) with a smoking history of ≥ 10 pack years 5. Pregnancy, breast-feeding or planned pregnancy during the study.

Primary outcomes:
measure: 'Well-controlled Asthma Week' - a Derived Binary Variable (Yes/No)
timeFrame: Weekly, up to 52 weeks
Secondary outcomes:
measure: Number of Participants Experiencing at Least One Severe Asthma Exacerbation
timeFrame: Day 1 up to 52 weeks
measure: Number of Participants Experiencing at Least One Moderate or Severe Asthma Exacerbation
timeFrame: Day 1 up to 52 weeks
measure: Average Change From Baseline in Pre-dose Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Study weeks 0,4,16,28,40,52
measure: Average Change From Baseline in Morning Peak Expiratory Flow (PEF)
timeFrame: up to 52 weeks
measure: Average Change From Baseline in Evening PEF
timeFrame: up to 52 weeks
measure: Average Change From Baseline in Number of Inhalations of 'as Needed' Medication.
timeFrame: up to 52 weeks
measure: Average Change From Baseline in Asthma Symptom Score
timeFrame: up to 52 weeks
measure: Change From Baseline in the Percentage of Nighttime Awakenings Due to Asthma
timeFrame: up to 52 weeks
measure: Change From Baseline in Percentage of Symptom-free Days
timeFrame: up to 52 weeks
measure: Change From Baseline in Percentage of 'As Needed' Free Days
timeFrame: up to 52 weeks
measure: Change From Baseline in Percentage of Asthma Control Days
timeFrame: up to 52 weeks
measure: Number of Patients With Study Specific Asthma Related Discontinuation
timeFrame: up to 52 weeks
measure: Poorly Controlled Asthma Weeks
timeFrame: Weekly for up to 52 weeks
measure: Number of Participants Experiencing at Least One Occasion With Additional Steroids for Asthma
timeFrame: Day 1 up to 52 weeks
measure: Average Change From Baseline in Asthma Control Questionnaire (ACQ-5)
timeFrame: Study weeks 0,4,16,28,40,52
measure: Average Change From Baseline in Asthma Quality of Life Questionnaire; Standard Version (AQLQ(S))
timeFrame: Study weeks 0,16,28,40,52
measure: Percentage of Controller Use Days
timeFrame: up to 52 weeks
measure: Annual Severe Asthma Exacerbation Rate
timeFrame: up to 52 weeks
measure: Annual Moderate or Severe Asthma Exacerbation Rate
timeFrame: up to 52 weeks
Other outcomes:
Locations:
city: Bedford Park
country: Australia
facility: Research Site
city: Concord
country: Australia
facility: Research Site
city: Maroubra
country: Australia
facility: Research Site
city: Murdoch
country: Australia
facility: Research Site
city: Wollongong
country: Australia
facility: Research Site
city: Alphaville
country: Brazil
facility: Research Site
city: Botucatu
country: Brazil
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city: Porto Alegre
country: Brazil
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city: Porto Alegre
country: Brazil
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city: Porto Alegre
country: Brazil
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city: Salvador
country: Brazil
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city: Santo Andre
country: Brazil
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city: Sao Paulo
country: Brazil
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city: Sao Paulo
country: Brazil
facility: Research Site
city: Sorocaba
country: Brazil
facility: Research Site
city: Dupnitsa
country: Bulgaria
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city: Gotse Delchev
country: Bulgaria
facility: Research Site
city: Kozloduy
country: Bulgaria
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city: Pazardzhik
country: Bulgaria
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city: Plovdiv
country: Bulgaria
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city: Razgrad
country: Bulgaria
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city: Roman
country: Bulgaria
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city: Ruse
country: Bulgaria
facility: Research Site
city: Sandanski
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Varna
country: Bulgaria
facility: Research Site
city: Velingrad
country: Bulgaria
facility: Research Site
city: Vratsa
country: Bulgaria
facility: Research Site
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Sherwood Park
country: Canada
facility: Research Site
state: Alberta
city: Maple Ridge
country: Canada
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state: British Columbia
city: North Vancouver
country: Canada
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state: British Columbia
city: Vancouver
country: Canada
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state: British Columbia
city: Mount Pearl
country: Canada
facility: Research Site
state: Newfoundland and Labrador
city: St. John's
country: Canada
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state: Newfoundland and Labrador
city: Ajax
country: Canada
facility: Research Site
state: Ontario
city: Burlington
country: Canada
facility: Research Site
state: Ontario
city: Cornwall
country: Canada
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state: Ontario
city: Etobicoke
country: Canada
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state: Ontario
city: Hamilton
country: Canada
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state: Ontario
city: Kanata
country: Canada
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state: Ontario
city: London
country: Canada
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state: Ontario
city: Mississauga
country: Canada
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state: Ontario
city: Newmarket
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state: Ontario
city: North York
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state: Ontario
city: Ottawa
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state: Ontario
city: Sarnia
country: Canada
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state: Ontario
city: Toronto
country: Canada
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state: Ontario
city: Toronto
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state: Ontario
city: Windsor
country: Canada
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state: Ontario
city: Levis
country: Canada
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state: Quebec
city: Montreal
country: Canada
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state: Quebec
city: Montreal
country: Canada
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state: Quebec
city: Montreal
country: Canada
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state: Quebec
city: Pointe Claire
country: Canada
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state: Quebec
city: Quebec City
country: Canada
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state: Quebec
city: St Charles Borromee
country: Canada
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state: Quebec
city: Trois Rivieres
country: Canada
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state: Quebec
city: Victoriaville
country: Canada
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state: Quebec
city: Quebec
country: Canada
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city: Quebec
country: Canada
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city: Quebec
country: Canada
facility: Research Site
city: Quillota
country: Chile
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city: Santiago
country: Chile
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city: Santiago
country: Chile
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city: Santiago
country: Chile
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city: Santiago
country: Chile
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city: Talcahuano
country: Chile
facility: Research Site
city: Beijing
country: China
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city: Beijing
country: China
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city: Changsha
country: China
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city: Chengdu
country: China
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city: Chengdu
country: China
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city: Guangzhou
country: China
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city: Guangzhou
country: China
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city: Haikou
country: China
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city: Hohhot
country: China
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city: Nanchang
country: China
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city: Shanghai
country: China
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city: Shanghai
country: China
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city: Shanghai
country: China
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city: Shanghai
country: China
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city: Shanghai
country: China
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city: Shanghai
country: China
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city: Shenyang
country: China
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city: Wenzhou
country: China
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city: Wuhan
country: China
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city: Xi'an
country: China
facility: Research Site
city: Xi'an
country: China
facility: Research Site
city: Xiamen
country: China
facility: Research Site
city: Xuzhou
country: China
facility: Research Site
city: Balassagyarmat
country: Hungary
facility: Research Site
city: Berettyóújfalu
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
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city: Budapest
country: Hungary
facility: Research Site
city: Edelény
country: Hungary
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city: Hajdúnánás
country: Hungary
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city: Miskolc
country: Hungary
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city: Monor
country: Hungary
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city: Mátészalka
country: Hungary
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city: Nyírbátor
country: Hungary
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city: Nyíregyháza
country: Hungary
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city: Pécs
country: Hungary
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city: Pécs
country: Hungary
facility: Research Site
city: Szeged
country: Hungary
facility: Research Site
city: Bucheon-si
country: Korea, Republic of
facility: Research Site
city: Cheongju-si
country: Korea, Republic of
facility: Research Site
city: Cheongju-si
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
facility: Research Site
city: D.f.
country: Mexico
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city: Durango
country: Mexico
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city: Mexico
country: Mexico
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city: Monterrey
country: Mexico
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city: Morelia
country: Mexico
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city: México
country: Mexico
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city: México
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city: Villahermosa
country: Mexico
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city: Cusco
country: Peru
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city: Lima
country: Peru
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city: Lima
country: Peru
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country: Peru
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city: Piura
country: Peru
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city: Surco
country: Peru
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city: Lipa City
country: Philippines
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city: Manila
country: Philippines
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city: Manila
country: Philippines
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city: Pasig City
country: Philippines
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city: Quezon City
country: Philippines
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city: Białystok
country: Poland
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city: Białystok
country: Poland
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city: Elbląg
country: Poland
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city: Grodzisk Mazowiecki
country: Poland
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city: Grudziądz
country: Poland
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city: Kielce
country: Poland
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city: Kraków
country: Poland
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city: Kraków
country: Poland
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city: Kraków
country: Poland
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country: Poland
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city: Poznań
country: Poland
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city: Poznań
country: Poland
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city: Rzeszów
country: Poland
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country: Poland
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city: Skierniewice
country: Poland
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city: Strzelce Opolskie
country: Poland
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city: Szczecin
country: Poland
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city: Szczecin
country: Poland
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city: Słupca
country: Poland
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city: Tarnów
country: Poland
facility: Research Site
city: Trzebnica
country: Poland
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city: Turek
country: Poland
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city: Zabrze
country: Poland
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city: Łódź
country: Poland
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city: Łódź
country: Poland
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city: Łódź
country: Poland
facility: Research Site
city: Bragadiru
country: Romania
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city: Brasov
country: Romania
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city: Brasov
country: Romania
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city: Cluj-Napoca
country: Romania
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city: Constanta
country: Romania
facility: Research Site
city: Pitesti
country: Romania
facility: Research Site
city: Timisoara
country: Romania
facility: Research Site
city: Chelyabinsk
country: Russian Federation
facility: Research Site
city: Ekaterinburg
country: Russian Federation
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city: Ekaterinburg
country: Russian Federation
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city: Ekaterinburg
country: Russian Federation
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city: Gatchina
country: Russian Federation
facility: Research Site
city: Ivanovo
country: Russian Federation
facility: Research Site
city: Kazan
country: Russian Federation
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city: Kemerovo
country: Russian Federation
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city: Kemerovo
country: Russian Federation
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city: Krasnoyarsk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
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city: Moscow
country: Russian Federation
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city: Moscow
country: Russian Federation
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city: Moscow
country: Russian Federation
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city: Moscow
country: Russian Federation
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city: Nizhny Novgorod
country: Russian Federation
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city: Novosibirsk
country: Russian Federation
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city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Penza
country: Russian Federation
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city: Perm
country: Russian Federation
facility: Research Site
city: Perm
country: Russian Federation
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city: Petrozavodsk
country: Russian Federation
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city: Pyatigorsk
country: Russian Federation
facility: Research Site
city: Ryazan
country: Russian Federation
facility: Research Site
city: Saint - Petersburg
country: Russian Federation
facility: Research Site
city: Saint - Petersburg
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Saratov
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: St.Petersburg
country: Russian Federation
facility: Research Site
city: Ulyanovsk
country: Russian Federation
facility: Research Site
city: Vladikavkaz
country: Russian Federation
facility: Research Site
city: Volgograd
country: Russian Federation
facility: Research Site
city: Volgograd
country: Russian Federation
facility: Research Site
city: Voronezh
country: Russian Federation
facility: Research Site
city: Yaroslavl
country: Russian Federation
facility: Research Site
city: Yaroslavl
country: Russian Federation
facility: Research Site
city: Boksburg North
country: South Africa
facility: Research Site
city: Durban
country: South Africa
facility: Research Site
city: Durban
country: South Africa
facility: Research Site
city: Durban
country: South Africa
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
city: Middelburg
country: South Africa
facility: Research Site
city: Queenswood
country: South Africa
facility: Research Site
city: Stanger
country: South Africa
facility: Research Site
city: Verulam
country: South Africa
facility: Research Site
city: Cherkasy
country: Ukraine
facility: Research Site
city: Dnipropetrovsk
country: Ukraine
facility: Research Site
city: Ivano-Frankivsk
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Lutsk
country: Ukraine
facility: Research Site
city: Lutsk
country: Ukraine
facility: Research Site
city: Lviv
country: Ukraine
facility: Research Site
city: Odesa
country: Ukraine
facility: Research Site
city: Vinnytsia
country: Ukraine
facility: Research Site
city: Zaporizhzhya
country: Ukraine
facility: Research Site
city: Bath
country: United Kingdom
facility: Research Site
city: Coventry
country: United Kingdom
facility: Research Site
city: Leamington Spa
country: United Kingdom
facility: Research Site
city: Mortimer Reading
country: United Kingdom
facility: Research Site
city: Trowbridge
country: United Kingdom
facility: Research Site
city: Dong Nai
country: Vietnam
facility: Research Site
city: Hai Phong
country: Vietnam
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
city: Hochiminh
country: Vietnam
facility: Research Site
Study officials:
affiliation: McMaster University, Hamilton, Canada
name: Paul M O'Byrne, MB, FRCP(C), FRSC
role: PRINCIPAL_INVESTIGATOR
References:
citation: FitzGerald JM, O'Byrne PM, Bateman ED, Barnes PJ, Zheng J, Ivanov S, Lamarca R, Larsdotter U, Emerath U, Jansen G, Puu M, Alagappan VKT, Surmont F, Reddel HK. Safety of As-Needed Budesonide-Formoterol in Mild Asthma: Data from the Two Phase III SYGMA Studies. Drug Saf. 2021 Apr;44(4):467-478. doi: 10.1007/s40264-020-01041-z. Epub 2021 Feb 6.
citation: O'Byrne PM, FitzGerald JM, Bateman ED, Barnes PJ, Zheng J, Gustafson P, Lamarca R, Puu M, Keen C, Alagappan VKT, Reddel HK. Effect of a single day of increased as-needed budesonide-formoterol use on short-term risk of severe exacerbations in patients with mild asthma: a post-hoc analysis of the SYGMA 1 study. Lancet Respir Med. 2021 Feb;9(2):149-158. doi: 10.1016/S2213-2600(20)30416-1. Epub 2020 Oct 1.
citation: O'Byrne PM, FitzGerald JM, Bateman ED, Barnes PJ, Zhong N, Keen C, Jorup C, Lamarca R, Ivanov S, Reddel HK. Inhaled Combined Budesonide-Formoterol as Needed in Mild Asthma. N Engl J Med. 2018 May 17;378(20):1865-1876. doi: 10.1056/NEJMoa1715274.
citation: O'Byrne PM, FitzGerald JM, Zhong N, Bateman E, Barnes PJ, Keen C, Almqvist G, Pemberton K, Jorup C, Ivanov S, Reddel HK. The SYGMA programme of phase 3 trials to evaluate the efficacy and safety of budesonide/formoterol given 'as needed' in mild asthma: study protocols for two randomised controlled trials. Trials. 2017 Jan 10;18(1):12. doi: 10.1186/s13063-016-1731-4.
citation: Reddel HK, Busse WW, Pedersen S, Tan WC, Chen YZ, Jorup C, Lythgoe D, O'Byrne PM. Should recommendations about starting inhaled corticosteroid treatment for mild asthma be based on symptom frequency: a post-hoc efficacy analysis of the START study. Lancet. 2017 Jan 14;389(10065):157-166. doi: 10.1016/S0140-6736(16)31399-X. Epub 2016 Nov 30.