AsthmaPhase 3SYGMA2NCT02224157

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

A Phase 3 study testing budesonode bid + terbutaline 'as needed' in people with Asthma, run by AstraZeneca at 340 sites in 25 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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' Read more about this study

Who is it for?: Ages 12 to 130 years
Conditions the study is for: Asthma
What is being tested?: budesonode bid + terbutaline 'as needed'
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 4,215 participants
Where: 340 sitesin 25 countries
Study dates: 28 Nov 2014to 16 Aug 2017
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 12 to 130 years
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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
Male or Female, ≥12 years of age
Documented diagnosis of asthma for at least 6 months prior to Visit 1
Patients who are in need of GINA step 2 treatment
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
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
Patients should have reversible airway obstruction
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

Who cannot join

Patient has a history of life-threatening asthma including intubation and intensive care unit admission
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
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
Current or previous smoker with a smoking history of ≥ 10 pack years
Pregnancy, breast-feeding or planned pregnancy during the study

Trial locations and contacts

340 sites in 25 countries.

Country

City, postcode or hospital

340 sites in 25 countries

Russia44 sites

Research Site
Chelyabinsk, 454021
Research Site
Gatchina, 188300
Research Site
Ivanovo, 153005
Research Site
Izhevsk, 426035
Research Site
Kazan', 420012
Research Site
Kemerovo, 650000
Research Site
Kemerovo, 650002
Research Site
Kemerovo, 650066
Research Site
Moscow, 109240
Research Site
Moscow, 117630
Research Site
Moscow, 121309
Research Site
Moscow, 123182
Research Site
Moscow, 142160
Research Site
Novosibirsk, 630008
Research Site
Novosibirsk, 630051
Research Site
Omsk, 644043
Research Site
Penza, 440067
Research Site
Perm, 614000
Research Site
Pskov, 180007
Research Site
Saint Petersburg, 191144
Research Site
Saint Petersburg, 193231
Research Site
Saint Petersburg, 194044
Research Site
Saint Petersburg, 194100
Research Site
Saint Petersburg, 194291
Research Site
Saint Petersburg, 194354
Research Site
Saint Petersburg, 196211
Research Site
Saint Petersburg, 196240
Research Site
Saint Petersburg, 196247
Research Site
Saint Petersburg, 196657
Research Site
Saint Petersburg, 197022
Research Site
Saint Petersburg, 197342
Research Site
Saint Petersburg, 198205
Research Site
Saint Petersburg, 198260
Research Site
Saratov, 410012
Research Site
Saratov, 410053
Research Site
Tomsk, 634050
Research Site
Tver', 170642
Research Site
Ufa, 450000
Research Site
Ulyanovsk, 432009
Research Site
Vladikavkaz, 362007
Research Site
Volgograd, 400131
Research Site
Vsevolozhsk, 188640
Research Site
Yaroslavl, 150003
Research Site
Yekaterinburg, 620137

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Ukraine26 sites

Research Site
Cherkasy, 18009
Research Site
Chernihiv, 14034
Research Site
Chernivtsi, 58000
Research Site
Dnipro, 49074
Research Site
Ivano-Frankivsk, 76012
Research Site
Ivano-Frankivsk, 76018
Research Site
Kharkiv, 61035
Research Site
Kharkiv, 61039
Research Site
Kharkiv, 61058
Research Site
Kharkiv, 61075
Research Site
Kherson, 73000
Research Site
Kyiv, 02091
Research Site
Kyiv, 03037
Research Site
Kyiv, 03680
Research Site
Kyiv, 04050
Research Site
Lutsk, 43000
Research Site
Lviv, 79066
Research Site
Odesa, 65025
Research Site
Odesa, 65114
Research Site
Ternopil, 46000
Research Site
Uzhhorod, 88000
Research Site
Uzhhorod, 88009
Research Site
Uzhhorod, 88014
Research Site
Vinnytsia, 21001
Research Site
Zaporizhzhya, 69063
Research Site
Zaporizhzhya, 69068

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Germany22 sites

Research Site
Bad Lippspringe, 33175
Research Site
Berlin, 10119
Research Site
Berlin, 10367
Research Site
Berlin, 10629
Research Site
Berlin, 10787
Research Site
Berlin, 13507
Research Site
Cottbus, 03050
Research Site
Frankfurt am Main, 60389
Research Site
Geesthacht, 21502
Research Site
Großhansdorf, 22927
Research Site
Hamburg, 20354
Research Site
Hanover, D-30173
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Leipzig, 04103
Research Site
Leipzig, 04207
Research Site
Leipzig, 04357
Research Site
Lübeck, 23552
Research Site
Neu-Isenburg, 63263
Research Site
Oldenburg, 23758
Research Site
Reinfeld, 23858
Research Site
Rüdersdorf, 15562
Research Site
Schleswig, 24837
Research Site
Warendorf, 48231

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Hungary22 sites

Research Site
Aszód, 2170
Research Site
Balassagyarmat, 2660
Research Site
Berettyóújfalu, 4100
Research Site
Budapest, 1036
Research Site
Budapest, 1135
Research Site
Budapest, 1145
Research Site
Budapest, 1191
Research Site
Cegléd, 2700
Research Site
Érd, 2030
Research Site
Gödöllő, 2100
Research Site
Gyula, 5700
Research Site
Gyula, 5703
Research Site
Hajdúnánás, 4080
Research Site
Létavértes, 4281
Research Site
Makó, 6900
Research Site
Miskolc, 3529
Research Site
Mórahalom, 6782
Research Site
Pécs, 7635
Research Site
Siófok, 8600
Research Site
Szeged, H-6722
Research Site
Szombathely, 9700
Research Site
Vásárosnamény, 4800

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Bulgaria19 sites

Research Site
Blagoevgrad, 2700
Research Site
Pernik, 2300
Research Site
Petrich, 2850
Research Site
Pleven, 5800
Research Site
Razlog, 2760
Research Site
Sliven, 8800
Research Site
Smolyan, 4700
Research Site
Sofia, 1404
Research Site
Sofia, 1407
Research Site
Sofia, 1408
Research Site
Sofia, 1431
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Sofia, 1612
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Sofia, 1618
Research Site
Sofia
Research Site
Stara Zagora, 6000
Research Site
Varna, 9000
Research Site
Veliko Tarnovo, 5000
Research Site
Vidin, 3700
Research Site
Yambol, 8600

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Czechia19 sites

Research Site
Česká Lípa, 470 01
Research Site
Kladno, 272 00
Research Site
Kralupy nad Vltavou, 278 01
Research Site
Kutná Hora, 284 01
Research Site
Liberec, 460 01
Research Site
Neratovice, 277 01
Research Site
Ostrava, 709 00
Research Site
Ostrava, 728 80
Research Site
Pardubice, 532 03
Research Site
Pilsen, 301 00
Research Site
Pilsen, 304 60
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Prague, 142 00
Research Site
Prague, 150 00
Research Site
Prague, 169 00
Research Site
Rokycany, 337 22
Research Site
Rudna U Prahy, 252 19
Research Site
Tábor, 390 01
Research Site
Teplice, 415 01
Research Site
Žatec, 43801

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Slovakia19 sites

Research Site
Kežmarok, 060 01
Research Site
Komárno, 945 01
Research Site
Košice, 040 22
Research Site
Košice, 04022
Research Site
Levice, 934 01
Research Site
Liptovský Mikuláš, 031 01
Research Site
Lučenec, 984 01
Research Site
Nitra, 94901
Research Site
Nové Zámky, 94001
Research Site
Poprad, 058 01
Research Site
Poprad, 05801
Research Site
Rimavská Sobota, 979 01
Research Site
Ružomberok, 034 26
Research Site
Skalica, 90901
Research Site
Šurany, 94201
Research Site
Topoľčany, 95501
Research Site
Trebišov, 07701
Research Site
Žilina, 01008
Research Site
Zvolen, 96001

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Poland17 sites

Research Site
Bialystok, 15-044
Research Site
Bialystok, 15-430
Research Site
Giżycko, 11-500
Research Site
Kościan, 64-000
Research Site
Krakow, 31-559
Research Site
Lublin, 20-709
Research Site
Mrągowo, 11-700
Research Site
Ostrów Wielkopolski, 63-400
Research Site
Ostrowiec Świętokrzyski, 27-400
Research Site
Pabianice, 95-200
Research Site
Piła, 64-920
Research Site
Poznan, 60-685
Research Site
Poznan, 60-693
Research Site
Proszowice, 32-100
Research Site
Rzeszów, 35-205
Research Site
Warsaw, 02-106
Research Site
Zabrze, 41-800

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Brazil16 sites

Research Site
Botucatu, 18618-970
Research Site
Florianópolis, 88040-970
Research Site
Goiânia, 74110 030
Research Site
Porto Alegre, 9002-060
Research Site
Porto Alegre, 90020-060
Research Site
Porto Alegre, 90110-270
Research Site
Porto Alegre, 90610-000
Research Site
Porto Alegre, 91350-200
Research Site
Salvador, 41940-455
Research Site
Santo André, 09080-110
Research Site
São Paulo, 02189-000
Research Site
São Paulo, 04020-060
Research Site
São Paulo, 04101-000
Research Site
São Paulo, 04266-010
Research Site
São Paulo, 05403-900
Research Site
Sorocaba, 18040-425

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South Africa15 sites

Research Site
Bellville, 7530
Research Site
Boksburg North, 1460
Research Site
Cape Town, 7570
Research Site
Cape Town, 7764
Research Site
Durban, 4001
Research Site
Durban, 4037
Research Site
Durban, 4091
Research Site
Durban, 4092
Research Site
Johannesburg, 2001
Research Site
Johannesburg, 2188
Research Site
Lenasia, 1829
Research Site
Mowbray, 7700
Research Site
Panorama, 7500
Research Site
Phoenix, 4068
Research Site
Verulam, 4345

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South Korea15 sites

Research Site
Busan, 49201
Research Site
Cheongju-si, 28644
Research Site
Daegu, 42415
Research Site
Incheon, 405-760
Research Site
Seongnam-si, 13620
Research Site
Seoul, 03080
Research Site
Seoul, 03312
Research Site
Seoul, 04401
Research Site
Seoul, 05030
Research Site
Seoul, 05505
Research Site
Seoul, 06591
Research Site
Seoul, 135-710
Research Site
Suwon, 16247
Research Site
Uijeongbu-si, 11765
Research Site
Wŏnju, 26426

Other trials in South Korea

Spain14 sites

Research Site
Alicante, 03004
Research Site
Badalona, 08916
Research Site
Barcelona, 08025
Research Site
Barcelona, 08036
Research Site
Bilbao (Vizcaya), 48013
Research Site
Madrid, 28040
Research Site
Madrid, 28046
Research Site
Málaga, 29730
Research Site
Marbella (Málaga), 29603
Research Site
Oviedo, 33011
Research Site
Seville, 41013
Research Site
Seville, 41071
Research Site
Terrassa (Barcelona), 08227
Research Site
Valencia, 46017

Other trials in Spain

New Zealand13 sites

Research Site
Auckland, 0626
Research Site
Christchurch, 8024
Research Site
Christchurch, 8041
Research Site
Christchurch Central, 8011
Research Site
Grafton, 1010
Research Site
Hamilton West, 3204
Research Site
Maroubra, 2035
Research Site
New Lambton, 2310
Research Site
Newtown, 6242
Research Site
Rotorua, 3010
Research Site
South Brisbane, 4101
Research Site
Tauranga, 3143
Research Site
Wellington, 6021

Other trials in New Zealand

Mexico10 sites

Research Site
Chihuahua City, 31203
Research Site
Guadalajara, 44100
Research Site
Guadalajara, 44670
Research Site
Mérida, 97070
Research Site
México, 06720
Research Site
Mexico City, 6726
Research Site
San Juan del Río, 76800
Research Site
Tlanepantla, 54055
Research Site
Villahermosa, 86035
Research Site
Zapopan, 45200

Other trials in Mexico

Thailand10 sites

Research Site
Bangkok, 10330
Research Site
Bangkok, 10400
Research Site
Bangkok, 10600
Research Site
Bangkok, 10700
Research Site
Chon Buri, 20000
Research Site
Hat Yai, 90110
Research Site
Khon Kaen, 40002
Research Site
Muang,, 55000
Research Site
Nonthaburi, 11000
Research Site
Pathum Thani, 12120

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Peru9 sites

Research Site
Chancay, 15131
Research Site
Lima, 15033
Research Site
Lima, LIMA 01
Research Site
Lima, LIMA 21
Research Site
Lima, LIMA 27
Research Site
Lima, LIMA 32
Research Site
Lima Cercado, LIMA 1
Research Site
Miraflores, 15046
Research Site
Santa Beatriz, LIMA 14

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Romania9 sites

Research Site
Bragadiru, 077025
Research Site
Brasov, 500051
Research Site
Brasov, 500283
Research Site
Bucharest, 030303
Research Site
Constanța, 900002
Research Site
Constanța
Research Site
Deva, 330061
Research Site
Iași, 700115
Research Site
Piteşti, 110084

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Chile7 sites

Research Site
Curicó, 3341643
Research Site
Quillota, 2260000
Research Site
Santiago, 404366
Research Site
Santiago, 8207257
Research Site
Santiago, 8320000
Research Site
Talca, 3465584
Research Site
Viña del Mar, 2520000

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France6 sites

Research Site
Brii-sous-forges, 91640
Research Site
Colmar, 68000
Research Site
Joué-lès-Tours, 37300
Research Site
Nantes, 44277
Research Site
Nîmes, 30000
Research Site
Rezé, 44400

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Sweden6 sites

Research Site
Borås, 506 30
Research Site
Lund, 222 21
Research Site
Malmö, 21152
Research Site
Stockholm, 114 46
Research Site
Värnamo, 33185
Research Site
Västra Frölunda, 42144

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Vietnam6 sites

Research Site
Can Tho, 900000
Research Site
Hà Nội, 100000
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Hanoi, 100000
Research Site
Ho Chi Minh City, 700000
Research Site
Hochiminh, 700000
Research Site
Huế, 530000

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Colombia5 sites

Research Site
Barranquilla, 80001
Research Site
Bogotá, 110221
Research Site
Bogotá, 111211
Research Site
Bogotá, 111511
Research Site
Medellín, 5001000

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Philippines5 sites

Research Site
Lipa City, 4217
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Manila
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Pasig, 1600
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Quezon City, 1109
Research Site
Quezon City

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Saudi Arabia5 sites

Research Site
Dhahran, 131932
Research Site
Jeddah, 21499
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Jeddah, 22252
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Riyadh, 12371
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Riyadh, 12713

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Australia1 site

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Sydney, 2010

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About this study

Official title: A Clinical Study Comparing Symbicort 'as Needed' With Pulmicort Twice Daily Plus Terbutaline 'as Needed' in Adult and Adolescent Patients With Asthma

Read the 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'

Conditions: Asthma
Being tested: budesonide/formoterol 'as needed' + budesonide placebo bid, budesonode bid + terbutaline 'as needed'
Medical subject headings: Asthma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

budesonide/formoterol 'as needed' + budesonide placebo bidDrug
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
budesonode bid + terbutaline 'as needed'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

Study groups in NCT02224157
Study group	Role	What they receive
Symbicort "as needed"+placebo Pulmicort bid	Experimental	Symbicort (budesonide/formoterol) Turbuhaler 160/4.5 μg 'as needed' + Placebo Pulmicort Turbuhaler 200 μg bid Receives: Drug: budesonide/formoterol 'as needed' + budesonide placebo bid
Pulmicort bid + terbutaline "as needed"	Active comparator	Pulmicort 200 μg Turbuhaler bid + terbutaline 0.4 mg Turbuhaler 'as needed' Receives: Drug: budesonode bid + terbutaline 'as needed'

What is being measured

The primary outcome is the main question the study is designed to answer.

Annual Severe Asthma Exacerbation Rate - Non-inferiority Analysis
Severe asthma exacerbations over the randomised treatment period, negative binomial model for non-inferiority test evaluation
Measured: up to 52 weeks
Annual Severe Asthma Exacerbation Rate - Superiority Analysis
Severe asthma exacerbations over the randomised treatment period, negative binomial model for superiority test evaluation
Measured: up to 52 weeks

Secondary outcomes (8)

Number of Participants Experiencing at Least One Severe Asthma Exacerbation
A severe exacerbation is defined as a deterioration of asthma requiring any of the following: use of systemic glucocorticosteroids (GCS) for at least 3 days, inpatient hospitalization, or emergency room visit due to asthma that required systemic steroids.
Measured: Day 1 up to 52 weeks
Average Change From Baseline in Pre-bronchodilator FEV1
The average change from baseline (baseline defined by measurement at week 0, prior to first dose of IP) to the treatment period average assessed over the entire treatment period in pre-bronchodilator FEV1 was derived by computing a contrast for the mean across the post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis.
Measured: Study weeks 0,17, 34, 52
Number of Participants With Study Specific Asthma Related Discontinuation
The following two criteria lead to discontinuation from the IP due to asthma related events: A severe asthma exacerbation with duration for more than 3 weeks, and/or three severe asthma exacerbations during 6 months.
Measured: Day 1 up to 52 weeks
Average Change From Baseline in 'as Needed' Use
'As-needed' use change from baseline over the randomised treatment period. Baseline was defined as the last 10 days of the run-in period. 'As needed' use was calculated as the cumulative doses of 'as-needed' medication over the randomised treatment period divided by the follow-up time (number of days - 1). ie, average number of inhalations per day.
Measured: Week 0 up to 52 weeks
Change From Baseline in Percent of 'as Needed' Free Days
'As needed' free days (%) change from baseline during randomised treatment period. An 'as-needed' free day was defined as a day and night with no use of 'as needed' medication. Variable analysed is the percentage (%) of 'as-needed' free days during the randomised treatment period. Baseline is defined by the last 10 days of the run-in period.
Measured: Week 0 up to 52 weeks
Percentage of Controller Use Days
ICS controller use days (%) during the randomised treatment period is calculated as the cumulative days when any controller medication (containing ICS) was taken including maintenance (Pulmicort bid group) and 'as needed' medication (Symbicort 'as needed' group) and additional prescribed ICS for asthma (all treatment groups), divided by the number of days in the randomised treatment period.
Measured: Week 0 up to 52 weeks
Average Change From Baseline in Asthma Control Questionnaire (5-item Version) - ACQ-5 Score
ACQ questionnaire contains five questions on patients' symptoms, which are assessed on a 7-point scale from 0 (representing good control) to 6 (representing poor control). The score is the mean score of all questions for which responses are provided. The average change from baseline to treatment period average in ACQ-5 was derived by computing a contrast for the mean across all post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis.
Measured: Study weeks 0, 17, 34, 52
Average Change From Baseline in Asthma Quality of Life Questionnaire Standardised Version - AQLQ(S) Score
AQLQ(S) consists of 32 questions in 4 domains. Each question is assessed on a 7-point scale from 1 to 7, with higher values indicating better health-related quality of life. The overall score is calculated as the mean score of all 32 items. The average change from baseline to treatment period average in AQLQ(S) overall score was derived by computing a contrast for the mean across all post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis.
Measured: Study weeks 0,17, 34, 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Nov 201416 Aug 2017

First posted25 Aug 2014 (estimated)
Study start28 Nov 2014
Primary completion16 Aug 2017
Study completion16 Aug 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for AsthmaStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 4,215 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02224157
Sponsor's protocol ID: D589SC00003
Other IDs: 2013-004473-28
Acronym: SYGMA2
Status last verified: Nov 2019
First submitted: 19 Aug 2014
Last updated: 25 Nov 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 33548020
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.
PubMed 29768147
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.
PubMed 28069068
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.
PubMed 27912982

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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A Study to Learn About the Study Medicine Called PF-07275315 in People With Moderate-To-Severe Asthma
Asthma

All Asthma trials

Study at a glance

From the registry record, last updated by the sponsor on 25 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Clinical Study Comparing Symbicort 'as Needed' With Pulmicort Twice Daily Plus Terbutaline 'as Needed' in Adult and Adolescent Patients With Asthma
ClinicalTrials.gov ID: NCT02224157
Acronym / sponsor ID: SYGMA2 / D589SC00003
Conditions: Asthma
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 4,215 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: 28 Nov 2014 (actual)
Primary completion: 16 Aug 2017 (actual)
Study completion: 16 Aug 2017 (actual)
First posted: 25 Aug 2014 (estimated)
Results: Posted 25 Nov 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Symbicort "as needed"+placebo Pulmicort bid	Experimental	Drug: budesonide/formoterol 'as needed' + budesonide placebo bidSymbicort (budesonide/formoterol) Turbuhaler 160/4.5 μg 'as needed' + Placebo Pulmicort Turbuhaler 200 μg bid
Pulmicort bid + terbutaline "as needed"	Active comparator	Drug: budesonode bid + terbutaline 'as needed'Pulmicort 200 μg Turbuhaler bid + terbutaline 0.4 mg Turbuhaler 'as needed'

Who may qualify

Ages: 12 to 130 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (8 listed)

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
Male or Female, ≥12 years of age
Documented diagnosis of asthma for at least 6 months prior to Visit 1
Patients who are in need of GINA step 2 treatment
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

Key exclusion criteria (5 listed)

Patient has a history of life-threatening asthma including intubation and intensive care unit admission
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
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
Current or previous smoker with a smoking history of ≥ 10 pack years
Pregnancy, breast-feeding or planned pregnancy during the study

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
budesonide/formoterol 'as needed' + budesonide placebo bidSymbicort (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	Drug	Symbicort "as needed"+placebo Pulmicort bid
budesonode 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	Drug	Pulmicort bid + terbutaline "as needed"

Primary outcome

Annual Severe Asthma Exacerbation Rate - Non-inferiority Analysis
Time frame: up to 52 weeks
Severe asthma exacerbations over the randomised treatment period, negative binomial model for non-inferiority test evaluation
Annual Severe Asthma Exacerbation Rate - Superiority Analysis
Time frame: up to 52 weeks
Severe asthma exacerbations over the randomised treatment period, negative binomial model for superiority test evaluation

8 secondary outcomes

Number of Participants Experiencing at Least One Severe Asthma Exacerbation
Time frame: Day 1 up to 52 weeks
Average Change From Baseline in Pre-bronchodilator FEV1
Time frame: Study weeks 0,17, 34, 52
Number of Participants With Study Specific Asthma Related Discontinuation
Time frame: Day 1 up to 52 weeks
Average Change From Baseline in 'as Needed' Use
Time frame: Week 0 up to 52 weeks
Change From Baseline in Percent of 'as Needed' Free Days
Time frame: Week 0 up to 52 weeks
Percentage of Controller Use Days
Time frame: Week 0 up to 52 weeks
Average Change From Baseline in Asthma Control Questionnaire (5-item Version) - ACQ-5 Score
Time frame: Study weeks 0, 17, 34, 52
Average Change From Baseline in Asthma Quality of Life Questionnaire Standardised Version - AQLQ(S) Score
Time frame: Study weeks 0,17, 34, 52

Results and safety

Results posted to the registry on 25 Nov 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo Bid + Symbicort 'as Needed' (Experimental)	2,095	1,985
Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)	2,094	1,983

Primary outcome: Annual Severe Asthma Exacerbation Rate - Non-inferiority Analysis

Time frame: up to 52 weeks. Least squares mean (95% Confidence Interval). Unit: exacerbations per participant year

Measure	Placebo Bid + Symbicort 'as Needed' (Experimental) n = 2089	Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator) n = 2087
Value	0.11 (0.10 to 0.13)	0.12 (0.10 to 0.14)

Placebo Bid + Symbicort 'as Needed' (Experimental) vs Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator): Rate ratio: 0.97, Negative binomial model

Population analysed: Full analysis set

Primary outcome: Annual Severe Asthma Exacerbation Rate - Superiority Analysis

Time frame: up to 52 weeks. Least squares mean (95% Confidence Interval). Unit: exacerbations per participant year

Measure	Placebo Bid + Symbicort 'as Needed' (Experimental) n = 2089	Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator) n = 2087
Value	0.11 (0.10 to 0.13)	0.12 (0.10 to 0.14)

Placebo Bid + Symbicort 'as Needed' (Experimental) vs Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator): Rate ratio: 0.97 (95% CI 0.78 to 1.20), p = 0.754, Negative binomial model

Population analysed: Full analysis set

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were summarised from Visit 2 throughout the randomised treatment period and including the follow-up period until the last telephone follow-up, or the last contact. Serious adverse events were recorded from the time of informed consent throughout the randomised treatment period and including the folow-up period until last telephone follow-up or last contact.. Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo Bid + Symbicort 'as Needed' (Experimental)	66 of 2,089 (3.2%)	491 of 2,089 (23.5%)	1 of 2,089
Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)	73 of 2,087 (3.5%)	519 of 2,087 (24.9%)	1 of 2,087

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33548020FitzGerald 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.
Derived from this study: PubMed 29768147Bateman 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.
Derived from this study: PubMed 28069068O'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.
Derived from this study: PubMed 27912982Reddel 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.
D589SC00003-revised-csp-edition-4\_12Oct2016\_Redacted\_pdfaLink provided by the sponsor.
D589SC00003-statistical-analysis-plan-edition-2\_06SEP2017\_pdfaLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Carin Jorup, MD study director

AstraZeneca Research & Development

340 sites in 25 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing budesonode bid + terbutaline 'as needed' in people with Asthma, run by AstraZeneca at 340 sites in 25 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 340 sites in Russia, Ukraine, Germany, Hungary, Bulgaria and 20 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Annual Severe Asthma Exacerbation Rate - Non-inferiority Analysis (time frame: up to 52 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02224157, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2019.