A Clinical Study to Evaluate Symbicort Turbuhaler Used 'as Needed' in Adults and Adolescents With Asthma.

NCT ID: NCT02149199

Last Updated: 2019-11-15

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

3850 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-07-07

Study Completion Date

2017-08-02

Brief Summary

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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

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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'

Conditions

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Asthma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Symbicort "as needed"+placebo Pulmicort bid

Symbicort (budesonide/formoterol) Turbuhaler 160/4.5 μg 'as needed' + Placebo Pulmicort Turbuhaler 200 μg bid

Group Type EXPERIMENTAL

budesonide/formoterol 'as needed' + budesonide placebo bid

Intervention Type DRUG

Symbicort (budesonide/ formoterol) 160/4.5 μg powder for inhalation 'as needed' plus Pulmicort placebo 200 μg powder for inhalation, 1 inhalation twice daily (morning and evening), 52-week treatment

terbutaline "as needed"+placebo Pulmicort bid

terbutaline Turbuhaler 0.4 mg 'as needed' + placebo Pulmicort 200 μg Turbuhaler bid

Group Type ACTIVE_COMPARATOR

terbutaline 'as needed' + placebo budesonide bid

Intervention Type DRUG

Terbutaline 0.4 mg powder for inhalation 'as needed' plus placebo Pulmicort (budesonide) 200 μg powder for inhalation, 1 inhalation twice daily (morning and evening), 52-week treatment

Pulmicort bid + terbutaline "as needed"

Pulmicort 200 μg Turbuhaler bid + terbutaline 0.4 mg Turbuhaler 'as needed'

Group Type ACTIVE_COMPARATOR

budesonide bid + terbutaline 'as needed'

Intervention Type DRUG

Pulmicort (budesonide) 200 μg powder for inhalation, 1 inhalation twice daily (morning and evening) plus terbutaline 0.4 mg powder for inhalation 'as needed', 52-week treatment

Interventions

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budesonide/formoterol 'as needed' + budesonide placebo bid

Symbicort (budesonide/ formoterol) 160/4.5 μg powder for inhalation 'as needed' plus Pulmicort placebo 200 μg powder for inhalation, 1 inhalation twice daily (morning and evening), 52-week treatment

Intervention Type DRUG

terbutaline 'as needed' + placebo budesonide bid

Terbutaline 0.4 mg powder for inhalation 'as needed' plus placebo Pulmicort (budesonide) 200 μg powder for inhalation, 1 inhalation twice daily (morning and evening), 52-week treatment

Intervention Type DRUG

budesonide bid + terbutaline 'as needed'

Pulmicort (budesonide) 200 μg powder for inhalation, 1 inhalation twice daily (morning and evening) plus terbutaline 0.4 mg powder for inhalation 'as needed', 52-week treatment

Intervention Type DRUG

Eligibility Criteria

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Inclusion 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

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.
Minimum Eligible Age

12 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Paul M O'Byrne, MB, FRCP(C), FRSC

Role: PRINCIPAL_INVESTIGATOR

McMaster University, Hamilton, Canada

Locations

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Bedford Park, , Australia

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Concord, , Australia

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Maroubra, , Australia

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Murdoch, , Australia

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Wollongong, , Australia

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Alphaville, , Brazil

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Botucatu, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Salvador, , Brazil

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Santo André, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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Sorocaba, , Brazil

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Dupnitsa, , Bulgaria

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Gotse Delchev, , Bulgaria

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Kozloduy, , Bulgaria

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Pazardzhik, , Bulgaria

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Plovdiv, , Bulgaria

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Razgrad, , Bulgaria

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Roman, , Bulgaria

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Rousse, , Bulgaria

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Sandanski, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Velingrad, , Bulgaria

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Vratsa, , Bulgaria

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Edmonton, Alberta, Canada

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Sherwood Park, Alberta, Canada

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Maple Ridge, British Columbia, Canada

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North Vancouver, British Columbia, Canada

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Vancouver, British Columbia, Canada

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Mount Pearl, Newfoundland and Labrador, Canada

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St. John's, Newfoundland and Labrador, Canada

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Ajax, Ontario, Canada

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Burlington, Ontario, Canada

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Cornwall, Ontario, Canada

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Etobicoke, Ontario, Canada

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Hamilton, Ontario, Canada

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Kanata, Ontario, Canada

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London, Ontario, Canada

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Mississauga, Ontario, Canada

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Newmarket, Ontario, Canada

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North York, Ontario, Canada

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Ottawa, Ontario, Canada

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Sarnia, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Windsor, Ontario, Canada

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Lévis, Quebec, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Pointe-Claire, Quebec, Canada

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Québec, Quebec, Canada

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Québec, Quebec, Canada

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Québec, Quebec, Canada

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Québec, Quebec, Canada

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Saint-Charles-Borromée, Quebec, Canada

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Trois-Rivières, Quebec, Canada

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Victoriaville, Quebec, Canada

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Quillota, , Chile

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Santiago, , Chile

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Santiago, , Chile

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Santiago, , Chile

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Santiago, , Chile

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Talcahuano, , Chile

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Beijing, , China

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Beijing, , China

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Changsha, , China

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Chengdu, , China

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Chengdu, , China

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Guangzhou, , China

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Guangzhou, , China

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Haikou, , China

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Hohhot, , China

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Nanchang, , China

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Shanghai, , China

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Shanghai, , China

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Shanghai, , China

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Shanghai, , China

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Shenyang, , China

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Wenzhou, , China

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Wuhan, , China

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Xi'an, , China

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Xi'an, , China

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Xiamen, , China

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Xuzhou, , China

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Balassagyarmat, , Hungary

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Berettyóújfalu, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Edelény, , Hungary

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Hajdúnánás, , Hungary

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Mátészalka, , Hungary

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Miskolc, , Hungary

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Monor, , Hungary

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Nyírbátor, , Hungary

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Nyíregyháza, , Hungary

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Pécs, , Hungary

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Pécs, , Hungary

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Szeged, , Hungary

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D.F., , Mexico

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Durango, , Mexico

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México, , Mexico

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México, , Mexico

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México, , Mexico

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Monterrey, , Mexico

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Morelia, , Mexico

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Villahermosa, , Mexico

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Cusco, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Piura, , Peru

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Surco, , Peru

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Lipa City, , Philippines

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Manila, , Philippines

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Manila, , Philippines

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Pasig, , Philippines

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Quezon City, , Philippines

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Bialystok, , Poland

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Bialystok, , Poland

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Elblag, , Poland

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Grodzisk Mazowiecki, , Poland

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Grudziądz, , Poland

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Kielce, , Poland

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Krakow, , Poland

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Krakow, , Poland

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Lodz, , Poland

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Lodz, , Poland

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Lodz, , Poland

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Poznan, , Poland

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Poznan, , Poland

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Rzeszów, , Poland

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Rzeszów, , Poland

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Skierniewice, , Poland

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Strzelce Opolskie, , Poland

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Szczecin, , Poland

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Szczecin, , Poland

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Słupca, , Poland

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Tarnów, , Poland

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Trzebnica, , Poland

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Turek, , Poland

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Zabrze, , Poland

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Bragadiru, , Romania

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Brasov, , Romania

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Brasov, , Romania

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Cluj-Napoca, , Romania

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Constanța, , Romania

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Piteşti, , Romania

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Timișoara, , Romania

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Chelyabinsk, , Russia

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Gatchina, , Russia

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Ivanovo, , Russia

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Kazan', , Russia

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Kemerovo, , Russia

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Kemerovo, , Russia

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Krasnoyarsk, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Nizhny Novgorod, , Russia

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Novosibirsk, , Russia

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Novosibirsk, , Russia

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Penza, , Russia

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Perm, , Russia

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Perm, , Russia

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Petrozavodsk, , Russia

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Pyatigorsk, , Russia

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Ryazan, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saratov, , Russia

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Ulyanovsk, , Russia

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Vladikavkaz, , Russia

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Volgograd, , Russia

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Volgograd, , Russia

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Voronezh, , Russia

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Yaroslavl, , Russia

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Yaroslavl, , Russia

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Yekaterinburg, , Russia

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Yekaterinburg, , Russia

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Yekaterinburg, , Russia

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Boksburg North, , South Africa

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Durban, , South Africa

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Durban, , South Africa

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Durban, , South Africa

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Johannesburg, , South Africa

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Johannesburg, , South Africa

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KwaDukuza, , South Africa

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Middelburg, , South Africa

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Queenswood, , South Africa

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Verulam, , South Africa

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Bucheon-si, , South Korea

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Cheongju-si, , South Korea

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Cheongju-si, , South Korea

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Incheon, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Cherkasy, , Ukraine

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Dnipropetrovsk, , Ukraine

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Ivano-Frankivsk, , Ukraine

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Kharkiv, , Ukraine

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Kharkiv, , Ukraine

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Kharkiv, , Ukraine

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Kharkiv, , Ukraine

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Kharkiv, , Ukraine

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Kharkiv, , Ukraine

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Kyiv, , Ukraine

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Kyiv, , Ukraine

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Kyiv, , Ukraine

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Lutsk, , Ukraine

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Lutsk, , Ukraine

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Lviv, , Ukraine

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Odesa, , Ukraine

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Vinnytsia, , Ukraine

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Zaporizhzhya, , Ukraine

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Bath, , United Kingdom

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Coventry, , United Kingdom

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Mortimer Reading, , United Kingdom

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Royal Leamington Spa, , United Kingdom

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Trowbridge, , United Kingdom

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Haiphong, , Vietnam

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Hanoi, , Vietnam

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Ho Chi Minh City, , Vietnam

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Ho Chi Minh City, , Vietnam

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Hochiminh, , Vietnam

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Đông Nãi, , Vietnam

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Countries

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Australia Brazil Bulgaria Canada Chile China Hungary Mexico Peru Philippines Poland Romania Russia South Africa South Korea Ukraine United Kingdom Vietnam

References

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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.

Reference Type DERIVED
PMID: 33548020 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33010810 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29768149 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28069068 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27912982 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Related Links

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Other Identifiers

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2013-004474-96

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D589SC00001

Identifier Type: -

Identifier Source: org_study_id

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