Clinical trial NCT02224157: 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 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: 2014-08-25
Enrollment: 4215
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 Pulmicort (budesonide) Turbuhaler twice daily plus terbutaline Turbuhaler 'as needed'

Detailed description: A 52-week, double-blind, randomised, multi-centre, phase III, parallel-group 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 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 GINA step 2 treatment
5. Patients treated with a short acting inhaled bronchodilator(s) only should have pre-bronchodilator FEV1 ≥ 60 % of predicted normal (PN) and post-bronchodilator FEV1 ≥ 80 % PN
6. Patients treated with low stable dose of ICS or leukotriene antagonists in addition to short acting inhaled 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 short acting inhaled bronchodilator(s) within 30 days prior to Visit 1 and from Visit 1 until randomization
3. Patient has required treatment with oral, rectal or parenteral GCS within 30 days and/or depot parenteral GCS within 12 weeks prior to Visit 1
4. Current or previous smoker with a smoking history of ≥ 10 pack years
5. Pregnancy, breast-feeding or planned pregnancy during the study

Primary outcomes:
measure: Annual Severe Asthma Exacerbation Rate - Non-inferiority Analysis
timeFrame: up to 52 weeks
measure: Annual Severe Asthma Exacerbation Rate - Superiority Analysis
timeFrame: 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: Average Change From Baseline in Pre-bronchodilator FEV1
timeFrame: Study weeks 0,17, 34, 52
measure: Number of Participants With Study Specific Asthma Related Discontinuation
timeFrame: Day 1 up to 52 weeks
measure: Average Change From Baseline in 'as Needed' Use
timeFrame: Week 0 up to 52 weeks
measure: Change From Baseline in Percent of 'as Needed' Free Days
timeFrame: Week 0 up to 52 weeks
measure: Percentage of Controller Use Days
timeFrame: Week 0 up to 52 weeks
measure: Average Change From Baseline in Asthma Control Questionnaire (5-item Version) - ACQ-5 Score
timeFrame: Study weeks 0, 17, 34, 52
measure: Average Change From Baseline in Asthma Quality of Life Questionnaire Standardised Version - AQLQ(S) Score
timeFrame: Study weeks 0,17, 34, 52
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Research Site
city: Botucatu
country: Brazil
facility: Research Site
city: Florianopolis
country: Brazil
facility: Research Site
city: Goiania
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Salvador
country: Brazil
facility: Research Site
city: Santo Andre
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Sorocaba
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Blagoevgrad
country: Bulgaria
facility: Research Site
city: Pernik
country: Bulgaria
facility: Research Site
city: Petrich
country: Bulgaria
facility: Research Site
city: Pleven
country: Bulgaria
facility: Research Site
city: Razlog
country: Bulgaria
facility: Research Site
city: Sliven
country: Bulgaria
facility: Research Site
city: Smolyan
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: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Stara Zagora
country: Bulgaria
facility: Research Site
city: Varna
country: Bulgaria
facility: Research Site
city: Veliko Tarnovo
country: Bulgaria
facility: Research Site
city: Vidin
country: Bulgaria
facility: Research Site
city: Yambol
country: Bulgaria
facility: Research Site
city: Curico
country: Chile
facility: Research Site
city: Quillota
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Talca
country: Chile
facility: Research Site
city: Viña del Mar
country: Chile
facility: Research Site
city: Barranquilla
country: Colombia
facility: Research Site
city: Bogota
country: Colombia
facility: Research Site
city: Bogotá
country: Colombia
facility: Research Site
city: Bogotá
country: Colombia
facility: Research Site
city: Medellin
country: Colombia
facility: Research Site
city: Ceska Lipa
country: Czechia
facility: Research Site
city: Kladno
country: Czechia
facility: Research Site
city: Kralupy nad Vltavou
country: Czechia
facility: Research Site
city: Kutna Hora
country: Czechia
facility: Research Site
city: Liberec 1
country: Czechia
facility: Research Site
city: Neratovice
country: Czechia
facility: Research Site
city: Ostrava
country: Czechia
facility: Research Site
city: Ostrava
country: Czechia
facility: Research Site
city: Pardubice
country: Czechia
facility: Research Site
city: Plzen
country: Czechia
facility: Research Site
city: Plzen
country: Czechia
facility: Research Site
city: Praha 4
country: Czechia
facility: Research Site
city: Praha 5
country: Czechia
facility: Research Site
city: Praha
country: Czechia
facility: Research Site
city: Rokycany
country: Czechia
facility: Research Site
city: Rudna U Prahy
country: Czechia
facility: Research Site
city: Tabor
country: Czechia
facility: Research Site
city: Teplice
country: Czechia
facility: Research Site
city: Zatec
country: Czechia
facility: Research Site
city: Brii-sous-forges
country: France
facility: Research Site
city: Colmar
country: France
facility: Research Site
city: Joue-les-Tours
country: France
facility: Research Site
city: Nantes Cedex 2
country: France
facility: Research Site
city: Nimes
country: France
facility: Research Site
city: Reze
country: France
facility: Research Site
city: Bad Lippspringe
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Cottbus
country: Germany
facility: Research Site
city: Frankfurt/Main
country: Germany
facility: Research Site
city: Geesthacht
country: Germany
facility: Research Site
city: Großhansdorf
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Lübeck
country: Germany
facility: Research Site
city: Neu-Isenburg
country: Germany
facility: Research Site
city: Oldenburg
country: Germany
facility: Research Site
city: Reinfeld
country: Germany
facility: Research Site
city: Rüdersdorf
country: Germany
facility: Research Site
city: Schleswig
country: Germany
facility: Research Site
city: Warendorf
country: Germany
facility: Research Site
city: Aszód
country: Hungary
facility: Research Site
city: Balassagyarmat
country: Hungary
facility: Research Site
city: Berettyóújfalu
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Cegléd
country: Hungary
facility: Research Site
city: Gyula
country: Hungary
facility: Research Site
city: Gyula
country: Hungary
facility: Research Site
city: Gödöllő
country: Hungary
facility: Research Site
city: Hajdúnánás
country: Hungary
facility: Research Site
city: Létavértes
country: Hungary
facility: Research Site
city: Makó
country: Hungary
facility: Research Site
city: Miskolc
country: Hungary
facility: Research Site
city: Mórahalom
country: Hungary
facility: Research Site
city: Pécs
country: Hungary
facility: Research Site
city: Siófok
country: Hungary
facility: Research Site
city: Szeged
country: Hungary
facility: Research Site
city: Szombathely
country: Hungary
facility: Research Site
city: Vásárosnamény
country: Hungary
facility: Research Site
city: Érd
country: Hungary
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Cheongju-si
country: Korea, Republic of
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Seongnam-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon-si
country: Korea, Republic of
facility: Research Site
city: Uijeongbu-si
country: Korea, Republic of
facility: Research Site
city: Wonju-si
country: Korea, Republic of
facility: Research Site
city: Chihuahua
country: Mexico
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Mexico City
country: Mexico
facility: Research Site
city: Mérida
country: Mexico
facility: Research Site
city: México
country: Mexico
facility: Research Site
city: San Juan del Rio
country: Mexico
facility: Research Site
city: Tlanepantla
country: Mexico
facility: Research Site
city: Villahermosa
country: Mexico
facility: Research Site
city: Zapopan
country: Mexico
facility: Research Site
city: Auckland
country: New Zealand
facility: Research Site
city: Christchurch Central
country: New Zealand
facility: Research Site
city: Christchurch
country: New Zealand
facility: Research Site
city: Christchurch
country: New Zealand
facility: Research Site
city: Grafton
country: New Zealand
facility: Research Site
city: Hamilton West
country: New Zealand
facility: Research Site
city: Maroubra
country: New Zealand
facility: Research Site
city: New Lambton
country: New Zealand
facility: Research Site
city: Newtown
country: New Zealand
facility: Research Site
city: Rotorua
country: New Zealand
facility: Research Site
city: South Brisbane
country: New Zealand
facility: Research Site
city: Tauranga
country: New Zealand
facility: Research Site
city: Wellington
country: New Zealand
facility: Research Site
city: Cercado De Lima
country: Peru
facility: Research Site
city: Chancay
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Miraflores
country: Peru
facility: Research Site
city: Santa Beatriz
country: Peru
facility: Research Site
city: Lipa City
country: Philippines
facility: Research Site
city: Manila
country: Philippines
facility: Research Site
city: Pasig City
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: Białystok
country: Poland
facility: Research Site
city: Białystok
country: Poland
facility: Research Site
city: Giżycko
country: Poland
facility: Research Site
city: Kościan
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Mrągowo
country: Poland
facility: Research Site
city: Ostrowiec Świętokrzyski
country: Poland
facility: Research Site
city: Ostrów Wielkopolski
country: Poland
facility: Research Site
city: Pabianice
country: Poland
facility: Research Site
city: Pila
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Proszowice
country: Poland
facility: Research Site
city: Rzeszów
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Zabrze
country: Poland
facility: Research Site
city: Bragadiru
country: Romania
facility: Research Site
city: Brasov
country: Romania
facility: Research Site
city: Brasov
country: Romania
facility: Research Site
city: Bucharest
country: Romania
facility: Research Site
city: Constanta
country: Romania
facility: Research Site
city: Constanta
country: Romania
facility: Research Site
city: Deva
country: Romania
facility: Research Site
city: Iasi
country: Romania
facility: Research Site
city: Pitesti
country: Romania
facility: Research Site
city: Chelyabinsk
country: Russian Federation
facility: Research Site
city: Ekaterinburg
country: Russian Federation
facility: Research Site
city: Gatchina
country: Russian Federation
facility: Research Site
city: Ivanovo
country: Russian Federation
facility: Research Site
city: Izhevsk
country: Russian Federation
facility: Research Site
city: Kazan
country: Russian Federation
facility: Research Site
city: Kemerovo
country: Russian Federation
facility: Research Site
city: Kemerovo
country: Russian Federation
facility: Research Site
city: Kemerovo
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
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Omsk
country: Russian Federation
facility: Research Site
city: Penza
country: Russian Federation
facility: Research Site
city: Perm
country: Russian Federation
facility: Research Site
city: Pskov
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: 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: 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: St. Petersburg
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: Tomsk
country: Russian Federation
facility: Research Site
city: Tver
country: Russian Federation
facility: Research Site
city: Ufa
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: Vsevolozhsk
country: Russian Federation
facility: Research Site
city: Yaroslavl
country: Russian Federation
facility: Research Site
city: Dhahran
country: Saudi Arabia
facility: Research Site
city: Jeddah
country: Saudi Arabia
facility: Research Site
city: Jeddah
country: Saudi Arabia
facility: Research Site
city: Riyadh
country: Saudi Arabia
facility: Research Site
city: Riyadh
country: Saudi Arabia
facility: Research Site
city: Kezmarok
country: Slovakia
facility: Research Site
city: Komarno
country: Slovakia
facility: Research Site
city: Kosice
country: Slovakia
facility: Research Site
city: Kosice
country: Slovakia
facility: Research Site
city: Levice
country: Slovakia
facility: Research Site
city: Liptovsky Mikulas
country: Slovakia
facility: Research Site
city: Lucenec
country: Slovakia
facility: Research Site
city: Nitra
country: Slovakia
facility: Research Site
city: Nove Zamky
country: Slovakia
facility: Research Site
city: Poprad
country: Slovakia
facility: Research Site
city: Poprad
country: Slovakia
facility: Research Site
city: Rimavska Sobota
country: Slovakia
facility: Research Site
city: Ruzomberok
country: Slovakia
facility: Research Site
city: Skalica
country: Slovakia
facility: Research Site
city: Surany
country: Slovakia
facility: Research Site
city: Topolcany
country: Slovakia
facility: Research Site
city: Trebisov
country: Slovakia
facility: Research Site
city: Zilina
country: Slovakia
facility: Research Site
city: Zvolen
country: Slovakia
facility: Research Site
city: Bellville
country: South Africa
facility: Research Site
city: Boksburg North
country: South Africa
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Cape Town
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: Durban
country: South Africa
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
city: Lenasia
country: South Africa
facility: Research Site
city: Mowbray
country: South Africa
facility: Research Site
city: Panorama
country: South Africa
facility: Research Site
city: Phoenix
country: South Africa
facility: Research Site
city: Verulam
country: South Africa
facility: Research Site
city: Alicante
country: Spain
facility: Research Site
city: Badalona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Bilbao (Vizcaya)
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Marbella (Málaga)
country: Spain
facility: Research Site
city: Oviedo
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Terrassa (Barcelona)
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Borås
country: Sweden
facility: Research Site
city: Lund
country: Sweden
facility: Research Site
city: Malmo
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Värnamo
country: Sweden
facility: Research Site
city: Västra Frölunda
country: Sweden
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Chonburi
country: Thailand
facility: Research Site
city: Hat Yai
country: Thailand
facility: Research Site
city: Khon Kaen
country: Thailand
facility: Research Site
city: Muang,
country: Thailand
facility: Research Site
city: Nonthaburi
country: Thailand
facility: Research Site
city: Pathumthani
country: Thailand
facility: Research Site
city: Cherkasy
country: Ukraine
facility: Research Site
city: Chernihiv
country: Ukraine
facility: Research Site
city: Chernivtsi
country: Ukraine
facility: Research Site
city: Dnipro
country: Ukraine
facility: Research Site
city: Ivano-Frankivsk
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: Kherson
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: Kyiv
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: Odessa
country: Ukraine
facility: Research Site
city: Ternopil
country: Ukraine
facility: Research Site
city: Uzhgorod
country: Ukraine
facility: Research Site
city: Uzhgorod
country: Ukraine
facility: Research Site
city: Uzhgorod
country: Ukraine
facility: Research Site
city: Vinnytsia
country: Ukraine
facility: Research Site
city: Zaporizhzhya
country: Ukraine
facility: Research Site
city: Zaporizhzhya
country: Ukraine
facility: Research Site
city: Can Tho
country: Vietnam
facility: Research Site
city: Ha Noi
country: Vietnam
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
city: Hochiminh
country: Vietnam
facility: Research Site
city: Hue
country: Vietnam
facility: Research Site
Study officials:
affiliation: AstraZeneca Research & Development
name: Carin Jorup, MD
role: STUDY_DIRECTOR
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: Bateman ED, Reddel HK, O'Byrne PM, Barnes PJ, Zhong N, Keen C, Jorup C, Lamarca R, Siwek-Posluszna A, FitzGerald JM. As-Needed Budesonide-Formoterol versus Maintenance Budesonide in Mild Asthma. N Engl J Med. 2018 May 17;378(20):1877-1887. doi: 10.1056/NEJMoa1715275.
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.