A 6 Month Safety Study Comparing Symbicort With Inhaled Corticosteroid Only in Asthmatic Adults and Adolescents
Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT01444430
Collaborator
(none)
12,460
350
2
46
35.6
0.8
Study Details
Study Description
Brief Summary
The purpose of the study is to evaluate the safety of Symbicort compared to inhaled corticosteroid alone during 6 months in adult and adolescent patients with asthma
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
A 26 week, randomized, double-blind, parallel-group, active controlled, multicenter, multinational safety study evaluating the risk of serious asthma-related events during treatment with Symbicort®, a fixed combination of inhaled corticosteroid (ICS) (budesonide) and a long acting β2-agonist (LABA) (formoterol) as compared to treatment with ICS (budesonide) alone in adult and adolescent (≥12 years of age) patients with asthma.
Study Design
Study Type:
Interventional
Actual Enrollment
:
12460 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A 26 Week, Randomized, Double-blind, Parallel-group, Active Controlled, Multicenter, Multinational Safety Study Evaluating the Risk of Serious Asthma-related Events During Treatment With Symbicort®, a Fixed Combination of Inhaled Corticosteroid (ICS) (Budesonide) and a Long Acting β2-agonist (LABA) (Formoterol) as Compared to Treatment With ICS (Budesonide) Alone in Adult and Adolescent (≥12 Years of Age) Patients With Asthma
Study Start Date
:
Dec 1, 2011
Actual Primary Completion Date
:
Oct 1, 2015
Actual Study Completion Date
:
Oct 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 Symbicort |
Drug: Symbicort pMDI
Patients were randomized to Symbicort and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): Symbicort pMDI 80/4.5 μg x 2 actuations bid (morning and evening) or Symbicort pMDI 160/4.5 μg x 2 actuations bid (morning and evening), for oral inhalation.
|
| Active Comparator: 2 budesonide |
Drug: budesonide pMDI
Patients were randomized to budesonide and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): budesonide pMDI 80 μg x 2 actuations bid (morning and evening) or budesonide pMDI 160 μg x 2 actuations bid (morning and evening), for oral inhalation.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants Experiencing an Event in the Composite Endpoint (Asthma-related Death, Asthma-related Intubation or Asthma-related Hospitalization) [Up to 27 weeks]
Number of participants experiencing an event in the composite endpoint (asthma-related death, asthma-related intubation or asthma-related hospitalization), using events adjudicated and confirmed by the Joint Adjudication Committee. Cox proportional hazards model with terms for randomized treatment and strata for incoming control/asthma treatment was used to compare Symbicort and budesonide. Hazard ratios and 95% confidence intervals were estimated.
- Number of Participants Experiencing an Event Included in the Definition of Asthma Exacerbation [Up to 26 weeks]
Number of participants experiencing an event included in the definition of asthma exacerbation. An asthma exacerbation was defined as a deterioration of asthma requiring systemic corticosteroids for at least 3 days or an inpatient hospitalization or emergency room visit due to asthma that required systemic corticosteroids. Cox proportional hazards model with terms for randomized treatment and strata for incoming control/asthma treatment was used to compare Symbicort and budesonide. Hazard ratios and 95% confidence intervals were estimated.
Secondary Outcome Measures
- Percent of Days With no Asthma Symptoms [Daily up to 26 weeks]
Percent of days with no asthma symptoms during the randomized treatment period. Analysis of variance (ANOVA) model including the fixed factors of treatment and strata by incoming control/asthma treatment was used to compare Symbicort and budesonide.
- Percent of Days With Activity Limitation Due to Asthma [Daily up to 26 weeks]
Percent of days with activity limitation due to asthma during the randomized treatment period. Analysis of variance (ANOVA) model including the fixed factors of treatment and strata by incoming control/asthma treatment was used to compare Symbicort and budesonide.
- Mean Number of Puffs of Rescue Medication Per 24 Hours [Daily up to 26 weeks]
Mean number of puffs of rescue medication per day (24 hours) during the randomized treatment period. Analysis of variance (ANOVA) model including the fixed factors of treatment and strata by incoming control/asthma treatment was used to compare Symbicort and budesonide.
- Asthma Control Questionnaire (ACQ6) [baseline, day 28, day 84, day 182]
The outcome variable for ACQ6 was the difference between the average of values recorded during the treatment period (day 28, day 84 and day 182) and the baseline measure. Analysis of covariance (ANCOVA) model, including the fixed factors of treatment and strata by incoming control/asthma treatment and baseline ACQ6 as covariate was used to compare Symbicort and budesonide. The asthma control questionnaire, ACQ6, consists of six questions; all assessed on a 7-point scale from 0 to 6, where 0 represents good control and 6 represents poor control. The overall score is the mean of the responses to each of the six questions.
- Percent of Nights With Awakening(s) Due to Asthma [Daily up to 26 weeks]
Percent of nights with awakening(s) due to asthma during the randomized treatment period. Analysis of variance (ANOVA) model including the fixed factors of treatment and strata by incoming control/asthma treatment was used to compare Symbicort and budesonide.
- Number of Participants Experiencing Discontinuation of Investigational Product Due to a Protocol Defined Asthma Exacerbation [Up to 26 weeks]
Number of participants experiencing discontinuation of investigational product due to a protocol defined asthma exacerbation. An asthma exacerbation was defined as a deterioration of asthma requiring systemic corticosteroids for at least 3 days or an inpatient hospitalization or emergency room visit due to asthma that required systemic corticosteroids. Cox proportional hazards model with terms for randomized treatment and strata for incoming control/asthma treatment was used to compare Symbicort and budesonide. Hazard ratios and 95% confidence intervals were estimated.
Eligibility Criteria
Criteria
Ages Eligible for Study:
12 Years
to 130 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Provision of signed informed consent/ paediatric assent (if applicable) prior to any study specific procedures including medication withdrawal
-
Male or Female, ≥12 years of age
-
Documented clinical diagnosis of asthma for at least 1 year prior to Visit 2
-
Patient must have history of at least 1 asthma exacerbation including one of the following:
-
requiring treatment with systemic corticosteroids
-
an asthma-related hospitalization between 4 weeks and 12 months prior to randomization
-
Current Asthma Therapy: Patients must be appropriately using one of the treatments for asthma listed in the protocol combined with achieving certain results when recording an Asthma Control Questionnaire
Exclusion Criteria:
-
Patient has a history of life-threatening asthma. Defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea requiring non-invasive ventilatory support.
-
Patient has required treatment with systemic corticosteroids (tablets, suspensions or injectable) for any reason within 4 weeks prior to Visit 2
-
Patient has an ongoing exacerbation, defined as a worsening of asthma that requires treatment with systemic corticosteroids (tablets, suspension, or injectable)
-
An asthma exacerbation within 4 weeks of randomization or more than 4 separate exacerbations in the 12 months preceding randomization or more than 2 hospitalizations for treatment of asthma in the 12 months preceding randomization
-
Patient has a respiratory infection or other viral/bacterial illness, or is recovering from such an illness at the time of Visit 2 that, in the investigator's opinion, will interfere with the patient's lung function
-
Patient must not meet unstable asthma severity criteria as listed in the protocol
-
Peak expiratory flow must not be below 50% o predicted normal
-
Pregnancy, breast-feeding or planned pregnancy during the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Birmingham | Alabama | United States | |
| 2 | Research Site | Huntsville | Alabama | United States | |
| 3 | Research Site | Anchorage | Alaska | United States | |
| 4 | Research Site | Gilbert | Arizona | United States | |
| 5 | Research Site | Glendale | Arizona | United States | |
| 6 | Research Site | Mesa | Arizona | United States | |
| 7 | Research Site | Tucson | Arizona | United States | |
| 8 | Research Site | Fort Smith | Arkansas | United States | |
| 9 | Research Site | Little Rock | Arkansas | United States | |
| 10 | Research Site | Alhambra | California | United States | |
| 11 | Research Site | Anaheim | California | United States | |
| 12 | Research Site | Arvin | California | United States | |
| 13 | Research Site | Bellflower | California | United States | |
| 14 | Research Site | Buena Park | California | United States | |
| 15 | Research Site | Costa Mesa | California | United States | |
| 16 | Research Site | Encinitas | California | United States | |
| 17 | Research Site | Escondido | California | United States | |
| 18 | Research Site | Fountain Valley | California | United States | |
| 19 | Research Site | Glendale | California | United States | |
| 20 | Research Site | Long Beach | California | United States | |
| 21 | Research Site | Los Angeles | California | United States | |
| 22 | Research Site | Newport Beach | California | United States | |
| 23 | Research Site | Northridge | California | United States | |
| 24 | Research Site | Palmdale | California | United States | |
| 25 | Research Site | Pasadena | California | United States | |
| 26 | Research Site | Poway | California | United States | |
| 27 | Research Site | Riverside | California | United States | |
| 28 | Research Site | Roseville | California | United States | |
| 29 | Research Site | San Diego | California | United States | |
| 30 | Research Site | San Jose | California | United States | |
| 31 | Research Site | Santa Ana | California | United States | |
| 32 | Research Site | Stockton | California | United States | |
| 33 | Research Site | Tustin | California | United States | |
| 34 | Research Site | Walnut Creek | California | United States | |
| 35 | Research Site | Denver | Colorado | United States | |
| 36 | Research Site | Thornton | Colorado | United States | |
| 37 | Research Site | Norwalk | Connecticut | United States | |
| 38 | Research Site | Waterbury | Connecticut | United States | |
| 39 | Research Site | Altamonte Springs | Florida | United States | |
| 40 | Research Site | Clearwater | Florida | United States | |
| 41 | Research Site | DeLand | Florida | United States | |
| 42 | Research Site | Fort Lauderdale | Florida | United States | |
| 43 | Research Site | Fort Myers | Florida | United States | |
| 44 | Research Site | Gainesville | Florida | United States | |
| 45 | Research Site | Hialeah | Florida | United States | |
| 46 | Research Site | Jacksonville | Florida | United States | |
| 47 | Research Site | Kissimmee | Florida | United States | |
| 48 | Research Site | Leesburg | Florida | United States | |
| 49 | Research Site | Lehigh Acres | Florida | United States | |
| 50 | Research Site | Lynn Haven | Florida | United States | |
| 51 | Research Site | Miami Beach | Florida | United States | |
| 52 | Research Site | Miami | Florida | United States | |
| 53 | Research Site | Ocoee | Florida | United States | |
| 54 | Research Site | Opalocka | Florida | United States | |
| 55 | Research Site | Orlando | Florida | United States | |
| 56 | Research Site | Pembroke Pines | Florida | United States | |
| 57 | Research Site | Royal Palm Beach | Florida | United States | |
| 58 | Research Site | Tampa | Florida | United States | |
| 59 | Research Site | Calhoun | Georgia | United States | |
| 60 | Research Site | Conyers | Georgia | United States | |
| 61 | Research Site | Decatur | Georgia | United States | |
| 62 | Research Site | Gainesville | Georgia | United States | |
| 63 | Research Site | Savannah | Georgia | United States | |
| 64 | Research Site | Hayden Lake | Idaho | United States | |
| 65 | Research Site | Meridan | Idaho | United States | |
| 66 | Research Site | Kenilworth | Illinois | United States | |
| 67 | Research Site | Springfield | Illinois | United States | |
| 68 | Research Site | Anderson | Indiana | United States | |
| 69 | Research Site | Evansville | Indiana | United States | |
| 70 | Research Site | Michigan City | Indiana | United States | |
| 71 | Research Site | Ames | Iowa | United States | |
| 72 | Research Site | Council Bluffs | Iowa | United States | |
| 73 | Research Site | Fort Mitchell | Kentucky | United States | |
| 74 | Research Site | Lexington | Kentucky | United States | |
| 75 | Research Site | Owensboro | Kentucky | United States | |
| 76 | Research Site | Lafayette | Louisiana | United States | |
| 77 | Research Site | Lake Charles | Louisiana | United States | |
| 78 | Research Site | Shreveport | Louisiana | United States | |
| 79 | Research Site | Baltimore | Maryland | United States | |
| 80 | Research Site | Lanham | Maryland | United States | |
| 81 | Research Site | Watertown | Massachusetts | United States | |
| 82 | Research Site | Kalamazoo | Michigan | United States | |
| 83 | Research Site | Madison Hgts | Michigan | United States | |
| 84 | Research Site | Port Huron | Michigan | United States | |
| 85 | Research Site | Southfield | Michigan | United States | |
| 86 | Research Site | Sterling Heights | Michigan | United States | |
| 87 | Research Site | Ypsilanti | Michigan | United States | |
| 88 | Research Site | Duluth | Minnesota | United States | |
| 89 | Research Site | Edina | Minnesota | United States | |
| 90 | Research Site | Biloxi | Mississippi | United States | |
| 91 | Research Site | Jackson | Mississippi | United States | |
| 92 | Research Site | Vicksburg | Mississippi | United States | |
| 93 | Research Site | Bridgeton | Missouri | United States | |
| 94 | Research Site | Chesterfield | Missouri | United States | |
| 95 | Research Site | Kansas City | Missouri | United States | |
| 96 | Research Site | Springfield | Missouri | United States | |
| 97 | Research Site | St Louis | Missouri | United States | |
| 98 | Research Site | Bellevue | Nebraska | United States | |
| 99 | Research Site | Grand Island | Nebraska | United States | |
| 100 | Research Site | Omaha | Nebraska | United States | |
| 101 | Research Site | Verona | New Jersey | United States | |
| 102 | Research Site | Bronx | New York | United States | |
| 103 | Research Site | Great Neck | New York | United States | |
| 104 | Research Site | Hopewell Jct | New York | United States | |
| 105 | Research Site | New York | New York | United States | |
| 106 | Research Site | Rochester | New York | United States | |
| 107 | Research Site | Rockville Centre | New York | United States | |
| 108 | Research Site | Watertown | New York | United States | |
| 109 | Research Site | Cary | North Carolina | United States | |
| 110 | Research Site | Charlotte | North Carolina | United States | |
| 111 | Research Site | Greensboro | North Carolina | United States | |
| 112 | Research Site | Salisbury | North Carolina | United States | |
| 113 | Research Site | Wilmington | North Carolina | United States | |
| 114 | Research Site | Winston-Salem | North Carolina | United States | |
| 115 | Research Site | Fargo | North Dakota | United States | |
| 116 | Research Site | Cincinnati | Ohio | United States | |
| 117 | Research Site | Miamishburg | Ohio | United States | |
| 118 | Research Site | Stow | Ohio | United States | |
| 119 | Research Site | Oklahoma City | Oklahoma | United States | |
| 120 | Research Site | Bend | Oregon | United States | |
| 121 | Research Site | Abington | Pennsylvania | United States | |
| 122 | Research Site | Bryn Mawr | Pennsylvania | United States | |
| 123 | Research Site | Doylestown | Pennsylvania | United States | |
| 124 | Research Site | Phoenixville | Pennsylvania | United States | |
| 125 | Research Site | Pittsburgh | Pennsylvania | United States | |
| 126 | Research Site | Wyomissing | Pennsylvania | United States | |
| 127 | Research Site | Warwick | Rhode Island | United States | |
| 128 | Research Site | Charleston | South Carolina | United States | |
| 129 | Research Site | Greeneville | South Carolina | United States | |
| 130 | Research Site | Greenville | South Carolina | United States | |
| 131 | Research Site | Greer | South Carolina | United States | |
| 132 | Research Site | Indian Land | South Carolina | United States | |
| 133 | Research Site | Summerville | South Carolina | United States | |
| 134 | Research Site | Knoxville | Tennessee | United States | |
| 135 | Research Site | Nashville | Tennessee | United States | |
| 136 | Research Site | Austin | Texas | United States | |
| 137 | Research Site | Baytown | Texas | United States | |
| 138 | Research Site | Dallas | Texas | United States | |
| 139 | Research Site | Fort Worth | Texas | United States | |
| 140 | Research Site | Georgetown | Texas | United States | |
| 141 | Research Site | Houston | Texas | United States | |
| 142 | Research Site | Killeen | Texas | United States | |
| 143 | Research Site | McKinney | Texas | United States | |
| 144 | Research Site | Pharr | Texas | United States | |
| 145 | Research Site | Plano | Texas | United States | |
| 146 | Research Site | San Antonio | Texas | United States | |
| 147 | Research Site | Spring | Texas | United States | |
| 148 | Research Site | Sugar Land | Texas | United States | |
| 149 | Research Site | Sugarland | Texas | United States | |
| 150 | Research Site | Waco | Texas | United States | |
| 151 | Research Site | Layton | Utah | United States | |
| 152 | Research Site | South Burlington | Vermont | United States | |
| 153 | Research Site | Danville | Virginia | United States | |
| 154 | Research Site | Vienna | Virginia | United States | |
| 155 | Research Site | Virginia Beach | Virginia | United States | |
| 156 | Research Site | Seattle | Washington | United States | |
| 157 | Research Site | Spokane | Washington | United States | |
| 158 | Research Site | Tacoma | Washington | United States | |
| 159 | Research Site | La Crosse | Wisconsin | United States | |
| 160 | Research Site | Milwaukee | Wisconsin | United States | |
| 161 | Research Site | Buenos Aires | Argentina | ||
| 162 | Research Site | Ciudad de Buenos Aires | Argentina | ||
| 163 | Research Site | Córdoba | Argentina | ||
| 164 | Research Site | Mar del Plata | Argentina | ||
| 165 | Research Site | Monte Grande | Argentina | ||
| 166 | Research Site | Quilmes | Argentina | ||
| 167 | Research Site | Ranelagh | Argentina | ||
| 168 | Research Site | San Miguel de Tucuman | Argentina | ||
| 169 | Research Site | San Miguel de Tucumán | Argentina | ||
| 170 | Research Site | Barueri | Brazil | ||
| 171 | Research Site | Botucatu | Brazil | ||
| 172 | Research Site | Goiania | Brazil | ||
| 173 | Research Site | Juiz de Fora | Brazil | ||
| 174 | Research Site | Porto Alegre | Brazil | ||
| 175 | Research Site | Santo André | Brazil | ||
| 176 | Research Site | Sao Paulo | Brazil | ||
| 177 | Research Site | Gotse Delchev | Bulgaria | ||
| 178 | Research Site | Kozloduy | Bulgaria | ||
| 179 | Research Site | Petrich | Bulgaria | ||
| 180 | Research Site | Pleven | Bulgaria | ||
| 181 | Research Site | Razgrad | Bulgaria | ||
| 182 | Research Site | Razlog | Bulgaria | ||
| 183 | Research Site | Ruse | Bulgaria | ||
| 184 | Research Site | Sandanski | Bulgaria | ||
| 185 | Research Site | Sevlievo | Bulgaria | ||
| 186 | Research Site | Sofia | Bulgaria | ||
| 187 | Research Site | Stara Zagora | Bulgaria | ||
| 188 | Research Site | Varna | Bulgaria | ||
| 189 | Research Site | Vidin | Bulgaria | ||
| 190 | Research Site | Quillota | Chile | ||
| 191 | Research Site | Santiago | Chile | ||
| 192 | Research Site | Vina del Mar | Chile | ||
| 193 | Research Site | Bogotá | Colombia | ||
| 194 | Research Site | Cali | Colombia | ||
| 195 | Research Site | Manizales | Colombia | ||
| 196 | Research Site | Beroun | Czech Republic | ||
| 197 | Research Site | Breclav | Czech Republic | ||
| 198 | Research Site | Krnov | Czech Republic | ||
| 199 | Research Site | Kutna Hora | Czech Republic | ||
| 200 | Research Site | Litomerice | Czech Republic | ||
| 201 | Research Site | Ostrava | Czech Republic | ||
| 202 | Research Site | Plzen | Czech Republic | ||
| 203 | Research Site | Praha 10 | Czech Republic | ||
| 204 | Research Site | Praha 4 | Czech Republic | ||
| 205 | Research Site | Praha 8 | Czech Republic | ||
| 206 | Research Site | Rokycany | Czech Republic | ||
| 207 | Research Site | Angers | France | ||
| 208 | Research Site | Perpignan | France | ||
| 209 | Research Site | Tierce | France | ||
| 210 | Research Site | Berlin | Germany | ||
| 211 | Research Site | Hamburg | Germany | ||
| 212 | Research Site | Leipzig | Germany | ||
| 213 | Research Site | Marburg | Germany | ||
| 214 | Research Site | Bangalore | India | ||
| 215 | Research Site | Calicut | India | ||
| 216 | Research Site | Coimbatore | India | ||
| 217 | Research Site | Goa | India | ||
| 218 | Research Site | Hyderabad | India | ||
| 219 | Research Site | Mangalore | India | ||
| 220 | Research Site | Mysore | India | ||
| 221 | Research Site | Nagpur | India | ||
| 222 | Research Site | New Delhi | India | ||
| 223 | Research Site | Trivandrum | India | ||
| 224 | Research Site | Benevento | Italy | ||
| 225 | Research Site | Bologna | Italy | ||
| 226 | Research Site | Catanzaro | Italy | ||
| 227 | Research Site | Ferrara | Italy | ||
| 228 | Research Site | Genova | Italy | ||
| 229 | Research Site | Napoli | Italy | ||
| 230 | Research Site | Padova | Italy | ||
| 231 | Research Site | Palermo | Italy | ||
| 232 | Research Site | Roma | Italy | ||
| 233 | Research Site | Ansan-si | Korea, Republic of | ||
| 234 | Research Site | Cheonan-si | Korea, Republic of | ||
| 235 | Research Site | Cheongju-si | Korea, Republic of | ||
| 236 | Research Site | Jinju-si | Korea, Republic of | ||
| 237 | Research Site | Seongnam-si | Korea, Republic of | ||
| 238 | Research Site | Seoul | Korea, Republic of | ||
| 239 | Research Site | Durango | Mexico | ||
| 240 | Research Site | Guadalajara | Mexico | ||
| 241 | Research Site | Mexico | Mexico | ||
| 242 | Research Site | Monterey | Mexico | ||
| 243 | Research Site | Monterrey | Mexico | ||
| 244 | Research Site | Morelia | Mexico | ||
| 245 | Research Site | México | Mexico | ||
| 246 | Research Site | Santiago de Querétaro | Mexico | ||
| 247 | Research Site | Villahermosa | Mexico | ||
| 248 | Research Site | Zapopan | Mexico | ||
| 249 | Research Site | Ciudad de Panama | Panama | ||
| 250 | Research Site | Cusco | Peru | ||
| 251 | Research Site | Lima | Peru | ||
| 252 | Research Site | Iloilo City | Philippines | ||
| 253 | Research Site | Lipa City | Philippines | ||
| 254 | Research Site | Manila | Philippines | ||
| 255 | Research Site | Pasig City | Philippines | ||
| 256 | Research Site | Quezon City | Philippines | ||
| 257 | Research Site | Białystok | Poland | ||
| 258 | Research Site | Bydgoszcz | Poland | ||
| 259 | Research Site | Chęciny | Poland | ||
| 260 | Research Site | Gorzów Wlkp | Poland | ||
| 261 | Research Site | Karpacz | Poland | ||
| 262 | Research Site | Kraków | Poland | ||
| 263 | Research Site | Ostrów Wielkopolski | Poland | ||
| 264 | Research Site | Skarżysko Kamienna | Poland | ||
| 265 | Research Site | Strzelce Opolskie | Poland | ||
| 266 | Research Site | Szczecin | Poland | ||
| 267 | Research Site | Tarnów | Poland | ||
| 268 | Research Site | Turek | Poland | ||
| 269 | Research Site | Urszulin | Poland | ||
| 270 | Research Site | Wrocław | Poland | ||
| 271 | Research Site | Caguas | Puerto Rico | ||
| 272 | Research Site | San Juan | Puerto Rico | ||
| 273 | Research Site | Toa Baja | Puerto Rico | ||
| 274 | Research Site | Bragadiru | Romania | ||
| 275 | Research Site | Brasov | Romania | ||
| 276 | Research Site | Bucharest | Romania | ||
| 277 | Research Site | Bucuresti | Romania | ||
| 278 | Research Site | Cluj Napoca | Romania | ||
| 279 | Research Site | Constanta | Romania | ||
| 280 | Research Site | Craiova | Romania | ||
| 281 | Research Site | Deva | Romania | ||
| 282 | Research Site | Iasi | Romania | ||
| 283 | Research Site | Tg. Mures | Romania | ||
| 284 | Research Site | Ekaterinburg | Russian Federation | ||
| 285 | Research Site | Kazan | Russian Federation | ||
| 286 | Research Site | Moscow | Russian Federation | ||
| 287 | Research Site | Novosibirsk | Russian Federation | ||
| 288 | Research Site | Penza | Russian Federation | ||
| 289 | Research Site | Saint Petersburg | Russian Federation | ||
| 290 | Research Site | Saint-Petersburg | Russian Federation | ||
| 291 | Research Site | Saratov | Russian Federation | ||
| 292 | Research Site | St-Petersburg | Russian Federation | ||
| 293 | Research Site | St. Petersburg | Russian Federation | ||
| 294 | Research Site | StPetersburg | Russian Federation | ||
| 295 | Research Site | Vladikavkaz | Russian Federation | ||
| 296 | Research Site | Volgograd | Russian Federation | ||
| 297 | Research Site | Yaroslavl | Russian Federation | ||
| 298 | Research Site | Yekaterinburg | Russian Federation | ||
| 299 | Research Site | Bardejov | Slovakia | ||
| 300 | Research Site | Bratislava | Slovakia | ||
| 301 | Research Site | Dunajska Streda | Slovakia | ||
| 302 | Research Site | Komarno | Slovakia | ||
| 303 | Research Site | Kosice | Slovakia | ||
| 304 | Research Site | Liptovsky Mikulas | Slovakia | ||
| 305 | Research Site | Nitra | Slovakia | ||
| 306 | Research Site | Presov | Slovakia | ||
| 307 | Research Site | Ruzomberok | Slovakia | ||
| 308 | Research Site | Skalica | Slovakia | ||
| 309 | Research Site | Zilina | Slovakia | ||
| 310 | Research Site | Zvolen | Slovakia | ||
| 311 | Research Site | Boksburg North | South Africa | ||
| 312 | Research Site | Breyton | South Africa | ||
| 313 | Research Site | Cape Town | South Africa | ||
| 314 | Research Site | Durban | South Africa | ||
| 315 | Research Site | Johannesburg | South Africa | ||
| 316 | Research Site | Lenasia | South Africa | ||
| 317 | Research Site | Lyttleton | South Africa | ||
| 318 | Research Site | Pretoria | South Africa | ||
| 319 | Research Site | Umkomaas | South Africa | ||
| 320 | Research Site | Verulam | South Africa | ||
| 321 | Research Site | Bangkok | Thailand | ||
| 322 | Research Site | Hat Yai | Thailand | ||
| 323 | Research Site | Khon Kaen | Thailand | ||
| 324 | Research Site | Muang, | Thailand | ||
| 325 | Research Site | Naimuang | Thailand | ||
| 326 | Research Site | Dnipropetrovsk | Ukraine | ||
| 327 | Research Site | Donetsk | Ukraine | ||
| 328 | Research Site | Ivano-Frankivsk | Ukraine | ||
| 329 | Research Site | Kharkiv | Ukraine | ||
| 330 | Research Site | Kiev | Ukraine | ||
| 331 | Research Site | Odesa | Ukraine | ||
| 332 | Research Site | Poltava | Ukraine | ||
| 333 | Research Site | Uzhgorod | Ukraine | ||
| 334 | Research Site | Vinnitsa | Ukraine | ||
| 335 | Research Site | Zaporozye | Ukraine | ||
| 336 | Research Site | Bath | United Kingdom | ||
| 337 | Research Site | Belfast | United Kingdom | ||
| 338 | Research Site | Blackpool | United Kingdom | ||
| 339 | Research Site | Canterbury | United Kingdom | ||
| 340 | Research Site | Chippenham | United Kingdom | ||
| 341 | Research Site | Coventry | United Kingdom | ||
| 342 | Research Site | Crawley | United Kingdom | ||
| 343 | Research Site | Leamington Spa | United Kingdom | ||
| 344 | Research Site | Leicester | United Kingdom | ||
| 345 | Research Site | Stockport | United Kingdom | ||
| 346 | Research Site | Trowbridge | United Kingdom | ||
| 347 | Research Site | Watford | United Kingdom | ||
| 348 | Research Site | Westbury | United Kingdom | ||
| 349 | Research Site | Hanoi | Vietnam | ||
| 350 | Research Site | Ho Chi Minh | Vietnam |
Sponsors and Collaborators
- AstraZeneca
Investigators
- Study Director: Carin Jorup, AstraZeneca Pepparedsleden 1, 431 83 Mölndal
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01444430
Other Study ID Numbers:
- D5896C00027
- 2011-002790-28
First Posted:
Sep 30, 2011
Last Update Posted:
Dec 15, 2016
Last Verified:
Nov 1, 2016
Keywords provided by AstraZeneca
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | This study started with an assessment visit where inclusion/exclusion criteria were reviewed and informed consent obtained. Eligible patients were randomized at the next visit. Patients then entered a 26 weeks double-blind treatment period followed by a 1 week follow-up telephone contact. Patients were recruited in 25 countries with 25% in the US. |
|---|---|
| Pre-assignment Detail | Eligible adult and adolescent patients were stratified based upon assessment of ACQ and prior asthma therapy and randomized 1:1 to double-blind Symbicort or budesonide. 12460 patients were enrolled (informed consent received) and 11693 were randomized. |
| Arm/Group Title | Symbicort | Budesonide |
|---|---|---|
| Arm/Group Description | Patients were randomized to Symbicort and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): Symbicort pMDI 80/4.5 μg x 2 actuations bid (morning and evening) or Symbicort pMDI 160/4.5 μg x 2 actuations bid (morning and evening). | Patients were randomized to budesonide and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): budesonide pMDI 80 μg x 2 actuations bid (morning and evening) or budesonide pMDI 160 μg x 2 actuations bid (morning and evening). |
| Period Title: Overall Study | ||
| STARTED | 5846 | 5847 |
| COMPLETED | 5785 | 5766 |
| NOT COMPLETED | 61 | 81 |
Baseline Characteristics
| Arm/Group Title | Symbicort | Budesonide | Total |
|---|---|---|---|
| Arm/Group Description | Patients were randomized to Symbicort and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): Symbicort pMDI 80/4.5 μg x 2 actuations bid (morning and evening) or Symbicort pMDI 160/4.5 μg x 2 actuations bid (morning and evening). | Patients were randomized to budesonide and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): budesonide pMDI 80 μg x 2 actuations bid (morning and evening) or budesonide pMDI 160 μg x 2 actuations bid (morning and evening). | Total of all reporting groups |
| Overall Participants | 5846 | 5847 | 11693 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
43.4
(17.4)
|
43.5
(17.3)
|
43.5
(17.3)
|
| Gender (Count of Participants) | |||
| Female |
3849
65.8%
|
3820
65.3%
|
7669
65.6%
|
| Male |
1997
34.2%
|
2027
34.7%
|
4024
34.4%
|
| Race/Ethnicity, Customized (Number) [Number] | |||
| White |
4050
69.3%
|
4003
68.5%
|
8053
68.9%
|
| Black/African American |
396
6.8%
|
401
6.9%
|
797
6.8%
|
| Asian |
848
14.5%
|
907
15.5%
|
1755
15%
|
| Native Hawaiian/Pacific Islander |
3
0.1%
|
3
0.1%
|
6
0.1%
|
| American Indian/Alaska Native |
225
3.8%
|
207
3.5%
|
432
3.7%
|
| Other |
324
5.5%
|
326
5.6%
|
650
5.6%
|
Outcome Measures
| Title | Number of Participants Experiencing an Event in the Composite Endpoint (Asthma-related Death, Asthma-related Intubation or Asthma-related Hospitalization) |
|---|---|
| Description | Number of participants experiencing an event in the composite endpoint (asthma-related death, asthma-related intubation or asthma-related hospitalization), using events adjudicated and confirmed by the Joint Adjudication Committee. Cox proportional hazards model with terms for randomized treatment and strata for incoming control/asthma treatment was used to compare Symbicort and budesonide. Hazard ratios and 95% confidence intervals were estimated. |
| Time Frame | Up to 27 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) population comprised of all patients randomized to study drug. |
| Arm/Group Title | Symbicort | Budesonide |
|---|---|---|
| Arm/Group Description | Patients were randomized to Symbicort and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): Symbicort pMDI 80/4.5 μg x 2 actuations bid (morning and evening) or Symbicort pMDI 160/4.5 μg x 2 actuations bid (morning and evening). | Patients were randomized to budesonide and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): budesonide pMDI 80 μg x 2 actuations bid (morning and evening) or budesonide pMDI 160 μg x 2 actuations bid (morning and evening). |
| Measure Participants | 5846 | 5847 |
| Number [Participants] |
43
0.7%
|
40
0.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Symbicort, Budesonide |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The upper limit of the 95% CI of the hazard ratio will be used to assess statistical non-inferiority (non-inferiority margin=2). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.073 | |
| Confidence Interval |
(2-Sided) 95% 0.698 to 1.650 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants Experiencing an Event Included in the Definition of Asthma Exacerbation |
|---|---|
| Description | Number of participants experiencing an event included in the definition of asthma exacerbation. An asthma exacerbation was defined as a deterioration of asthma requiring systemic corticosteroids for at least 3 days or an inpatient hospitalization or emergency room visit due to asthma that required systemic corticosteroids. Cox proportional hazards model with terms for randomized treatment and strata for incoming control/asthma treatment was used to compare Symbicort and budesonide. Hazard ratios and 95% confidence intervals were estimated. |
| Time Frame | Up to 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The On treatment Analysis set comprised of all randomized patients and included data that corresponded to each patient's period of exposure to study drug plus 7 days after the last date of study drug treatment. |
| Arm/Group Title | Symbicort | Budesonide |
|---|---|---|
| Arm/Group Description | Patients were randomized to Symbicort and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): Symbicort pMDI 80/4.5 μg x 2 actuations bid (morning and evening) or Symbicort pMDI 160/4.5 μg x 2 actuations bid (morning and evening). | Patients were randomized to budesonide and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): budesonide pMDI 80 μg x 2 actuations bid (morning and evening) or budesonide pMDI 160 μg x 2 actuations bid (morning and evening). |
| Measure Participants | 5846 | 5847 |
| Number [Participants] |
539
9.2%
|
633
10.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Symbicort, Budesonide |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.835 | |
| Confidence Interval |
(2-Sided) 95% 0.745 to 0.937 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent of Days With no Asthma Symptoms |
|---|---|
| Description | Percent of days with no asthma symptoms during the randomized treatment period. Analysis of variance (ANOVA) model including the fixed factors of treatment and strata by incoming control/asthma treatment was used to compare Symbicort and budesonide. |
| Time Frame | Daily up to 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) population comprised of all patients randomized to study drug and had at least one entry of diary data after randomization. |
| Arm/Group Title | Symbicort | Budesonide |
|---|---|---|
| Arm/Group Description | Patients were randomized to Symbicort and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): Symbicort pMDI 80/4.5 μg x 2 actuations bid (morning and evening) or Symbicort pMDI 160/4.5 μg x 2 actuations bid (morning and evening). | Patients were randomized to budesonide and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): budesonide pMDI 80 μg x 2 actuations bid (morning and evening) or budesonide pMDI 160 μg x 2 actuations bid (morning and evening). |
| Measure Participants | 5784 | 5796 |
| Least Squares Mean (Standard Error) [Percentage of days] |
81.1
(0.4)
|
76.8
(0.4)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Symbicort, Budesonide |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 4.4 | |
| Confidence Interval |
(2-Sided) 95% 3.3 to 5.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.5 |
|
| Estimation Comments | ||
| Title | Percent of Days With Activity Limitation Due to Asthma |
|---|---|
| Description | Percent of days with activity limitation due to asthma during the randomized treatment period. Analysis of variance (ANOVA) model including the fixed factors of treatment and strata by incoming control/asthma treatment was used to compare Symbicort and budesonide. |
| Time Frame | Daily up to 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) population comprised of all patients randomized to study drug. The analysis set comprises of all patients with at least one day with asthma symptoms, i.e. the denominator is the number of days with asthma symptoms. |
| Arm/Group Title | Symbicort | Budesonide |
|---|---|---|
| Arm/Group Description | Patients were randomized to Symbicort and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): Symbicort pMDI 80/4.5 μg x 2 actuations bid (morning and evening) or Symbicort pMDI 160/4.5 μg x 2 actuations bid (morning and evening). | Patients were randomized to budesonide and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): budesonide pMDI 80 μg x 2 actuations bid (morning and evening) or budesonide pMDI 160 μg x 2 actuations bid (morning and evening). |
| Measure Participants | 4895 | 5045 |
| Least Squares Mean (Standard Error) [Percentage of days] |
19.7
(0.4)
|
19.1
(0.4)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Symbicort, Budesonide |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.272 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.6 | |
| Confidence Interval |
(2-Sided) 95% -0.5 to 1.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.6 |
|
| Estimation Comments | ||
| Title | Mean Number of Puffs of Rescue Medication Per 24 Hours |
|---|---|
| Description | Mean number of puffs of rescue medication per day (24 hours) during the randomized treatment period. Analysis of variance (ANOVA) model including the fixed factors of treatment and strata by incoming control/asthma treatment was used to compare Symbicort and budesonide. |
| Time Frame | Daily up to 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) population comprised of all patients randomized to study drug and had at least one entry of diary data after randomization. |
| Arm/Group Title | Symbicort | Budesonide |
|---|---|---|
| Arm/Group Description | Patients were randomized to Symbicort and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): Symbicort pMDI 80/4.5 μg x 2 actuations bid (morning and evening) or Symbicort pMDI 160/4.5 μg x 2 actuations bid (morning and evening). | Patients were randomized to budesonide and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): budesonide pMDI 80 μg x 2 actuations bid (morning and evening) or budesonide pMDI 160 μg x 2 actuations bid (morning and evening). |
| Measure Participants | 5784 | 5796 |
| Least Squares Mean (Standard Error) [Inhalations/day] |
0.8
(0.0)
|
0.9
(0.0)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Symbicort, Budesonide |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.2 to -0.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0 |
|
| Estimation Comments | ||
| Title | Asthma Control Questionnaire (ACQ6) |
|---|---|
| Description | The outcome variable for ACQ6 was the difference between the average of values recorded during the treatment period (day 28, day 84 and day 182) and the baseline measure. Analysis of covariance (ANCOVA) model, including the fixed factors of treatment and strata by incoming control/asthma treatment and baseline ACQ6 as covariate was used to compare Symbicort and budesonide. The asthma control questionnaire, ACQ6, consists of six questions; all assessed on a 7-point scale from 0 to 6, where 0 represents good control and 6 represents poor control. The overall score is the mean of the responses to each of the six questions. |
| Time Frame | baseline, day 28, day 84, day 182 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) population comprised of all patients randomized to study drug with at least one post-baseline ACQ6 score. |
| Arm/Group Title | Symbicort | Budesonide |
|---|---|---|
| Arm/Group Description | Patients were randomized to Symbicort and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): Symbicort pMDI 80/4.5 μg x 2 actuations bid (morning and evening) or Symbicort pMDI 160/4.5 μg x 2 actuations bid (morning and evening). | Patients were randomized to budesonide and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): budesonide pMDI 80 μg x 2 actuations bid (morning and evening) or budesonide pMDI 160 μg x 2 actuations bid (morning and evening). |
| Measure Participants | 5701 | 5698 |
| Least Squares Mean (Standard Error) [ACQ6 overall score change from baseline] |
-0.70
(0.01)
|
-0.62
(0.01)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Symbicort, Budesonide |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.08 | |
| Confidence Interval |
(2-Sided) 95% -0.10 to -0.06 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.01 |
|
| Estimation Comments | ||
| Title | Percent of Nights With Awakening(s) Due to Asthma |
|---|---|
| Description | Percent of nights with awakening(s) due to asthma during the randomized treatment period. Analysis of variance (ANOVA) model including the fixed factors of treatment and strata by incoming control/asthma treatment was used to compare Symbicort and budesonide. |
| Time Frame | Daily up to 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) population comprised of all patients randomized to study drug and had at least one entry of diary data after randomization. |
| Arm/Group Title | Symbicort | Budesonide |
|---|---|---|
| Arm/Group Description | Patients were randomized to Symbicort and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): Symbicort pMDI 80/4.5 μg x 2 actuations bid (morning and evening) or Symbicort pMDI 160/4.5 μg x 2 actuations bid (morning and evening). | Patients were randomized to budesonide and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): budesonide pMDI 80 μg x 2 actuations bid (morning and evening) or budesonide pMDI 160 μg x 2 actuations bid (morning and evening). |
| Measure Participants | 5784 | 5796 |
| Least Squares Mean (Standard Error) [Percentage of nights] |
4.0
(0.2)
|
4.7
(0.2)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Symbicort, Budesonide |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.004 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.6 | |
| Confidence Interval |
(2-Sided) 95% -1.0 to -0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.2 |
|
| Estimation Comments | ||
| Title | Number of Participants Experiencing Discontinuation of Investigational Product Due to a Protocol Defined Asthma Exacerbation |
|---|---|
| Description | Number of participants experiencing discontinuation of investigational product due to a protocol defined asthma exacerbation. An asthma exacerbation was defined as a deterioration of asthma requiring systemic corticosteroids for at least 3 days or an inpatient hospitalization or emergency room visit due to asthma that required systemic corticosteroids. Cox proportional hazards model with terms for randomized treatment and strata for incoming control/asthma treatment was used to compare Symbicort and budesonide. Hazard ratios and 95% confidence intervals were estimated. |
| Time Frame | Up to 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The On treatment Analysis set comprised of all randomized patients and included data that corresponded to each patient's period of exposure to study drug plus 7 days after the last date of study drug treatment. |
| Arm/Group Title | Symbicort | Budesonide |
|---|---|---|
| Arm/Group Description | Patients were randomized to Symbicort and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): Symbicort pMDI 80/4.5 μg x 2 actuations bid (morning and evening) or Symbicort pMDI 160/4.5 μg x 2 actuations bid (morning and evening). | Patients were randomized to budesonide and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): budesonide pMDI 80 μg x 2 actuations bid (morning and evening) or budesonide pMDI 160 μg x 2 actuations bid (morning and evening). |
| Measure Participants | 5846 | 5847 |
| Number [Participants] |
53
0.9%
|
71
1.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Symbicort, Budesonide |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.095 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.739 | |
| Confidence Interval |
(2-Sided) 95% 0.518 to 1.055 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | Serious adverse events (SAEs) and discontinuation of treatment with investigational product due to adverse event (DAEs) were recorded from the time of informed consent through the treatment period and including the follow-up period, up to 27 weeks. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | AEs were not collected unless they lead to discontinuation or qualified as an SAE. | |||
| Arm/Group Title | Symbicort | Budesonide | ||
| Arm/Group Description | Patients were randomized to Symbicort and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): Symbicort pMDI 80/4.5 μg x 2 actuations bid (morning and evening) or Symbicort pMDI 160/4.5 μg x 2 actuations bid (morning and evening). | Patients were randomized to budesonide and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): budesonide pMDI 80 μg x 2 actuations bid (morning and evening) or budesonide pMDI 160 μg x 2 actuations bid (morning and evening). | ||
All Cause Mortality |
||||
| Symbicort | Budesonide | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Symbicort | Budesonide | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 125/5846 (2.1%) | 123/5847 (2.1%) | ||
| Blood and lymphatic system disorders | ||||
| Lymphadenopathy mediastinal | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Pancytopenia | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Cardiac disorders | ||||
| Acute myocardial infarction | 1/5846 (0%) | 1 | 1/5847 (0%) | 1 |
| Angina pectoris | 3/5846 (0.1%) | 3 | 1/5847 (0%) | 1 |
| Angina unstable | 2/5846 (0%) | 2 | 1/5847 (0%) | 1 |
| Arrhythmia | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Atrial fibrillation | 0/5846 (0%) | 0 | 3/5847 (0.1%) | 3 |
| Atrial flutter | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Cardiac failure chronic | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Cardiac failure congestive | 2/5846 (0%) | 2 | 0/5847 (0%) | 0 |
| Cardiopulmonary failure | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Coronary artery disease | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Coronary artery insufficiency | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Hypertensive heart disease | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Mitral valve stenosis | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Myocardial infarction | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Myocardial ischaemia | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Myocarditis | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Supraventricular tachycardia | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Tachycardia | 0/5846 (0%) | 0 | 2/5847 (0%) | 2 |
| Ear and labyrinth disorders | ||||
| Vertigo | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Gastrointestinal disorders | ||||
| Abdominal hernia | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Abdominal pain | 2/5846 (0%) | 2 | 2/5847 (0%) | 2 |
| Abdominal pain upper | 0/5846 (0%) | 0 | 3/5847 (0.1%) | 3 |
| Colitis | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Colitis ulcerative | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Diarrhoea | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Dyspepsia | 1/5846 (0%) | 1 | 1/5847 (0%) | 1 |
| Erosive oesophagitis | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Food poisoning | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Gastric ulcer perforation | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Gastritis | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Gastrooesophageal reflux disease | 2/5846 (0%) | 2 | 2/5847 (0%) | 2 |
| Haematochezia | 1/5846 (0%) | 1 | 1/5847 (0%) | 1 |
| Haemorrhoids | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Hiatus hernia | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Inguinal hernia | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Intussusception | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Oesophagitis haemorrhagic | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Pancreatitis acute | 1/5846 (0%) | 1 | 1/5847 (0%) | 1 |
| Peritoneal haemorrhage | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Umbilical hernia | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| General disorders | ||||
| Chest pain | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Death | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Device dislocation | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Influenza like illness | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Non-cardiac chest pain | 1/5846 (0%) | 1 | 2/5847 (0%) | 2 |
| Hepatobiliary disorders | ||||
| Biliary colic | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Biliary dyskinesia | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Cholecystitis | 1/5846 (0%) | 1 | 1/5847 (0%) | 1 |
| Cholelithiasis | 2/5846 (0%) | 2 | 1/5847 (0%) | 1 |
| Hepatic cirrhosis | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Hepatic steatosis | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Hepatitis | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Immune system disorders | ||||
| Allergic granulomatous angiitis | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Anaphylactic reaction | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Anaphylactic shock | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Hypersensitivity | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Infections and infestations | ||||
| Abdominal abscess | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Acute sinusitis | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Appendicitis | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Bronchitis | 1/5846 (0%) | 1 | 1/5847 (0%) | 1 |
| Bronchitis bacterial | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Cellulitis | 1/5846 (0%) | 1 | 1/5847 (0%) | 1 |
| Clostridium difficile infection | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Cystitis | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Diarrhoea infectious | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Dysentery | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Gastroenteritis | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Gastroenteritis norovirus | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Haemophilus infection | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Herpes zoster | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Influenza | 0/5846 (0%) | 0 | 2/5847 (0%) | 2 |
| Lower respiratory tract infection bacterial | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Malaria | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Mycoplasma infection | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Nasopharyngitis | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Osteomyelitis | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Pharyngitis | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Pharyngotonsillitis | 1/5846 (0%) | 1 | 1/5847 (0%) | 1 |
| Pneumonia | 12/5846 (0.2%) | 12 | 6/5847 (0.1%) | 6 |
| Pneumonia bacterial | 2/5846 (0%) | 2 | 3/5847 (0.1%) | 3 |
| Postoperative wound infection | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Rhinitis | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Sepsis | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Sinusitis | 2/5846 (0%) | 2 | 1/5847 (0%) | 1 |
| Tuberculous pleurisy | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Upper respiratory tract infection bacterial | 0/5846 (0%) | 0 | 2/5847 (0%) | 2 |
| Injury, poisoning and procedural complications | ||||
| Ankle fracture | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Burns first degree | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Burns second degree | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Cervical vertebral fracture | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Contusion | 1/5846 (0%) | 1 | 1/5847 (0%) | 1 |
| Electric shock | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Femur fracture | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Foot fracture | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Incisional hernia | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Muscle strain | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Rib fracture | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Road traffic accident | 1/5846 (0%) | 1 | 1/5847 (0%) | 1 |
| Tibia fracture | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Ulna fracture | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Upper limb fracture | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Wound | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Investigations | ||||
| Blood pressure increased | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Heart rate irregular | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Metabolism and nutrition disorders | ||||
| Dehydration | 2/5846 (0%) | 2 | 0/5847 (0%) | 0 |
| Diabetic ketoacidosis | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Hyperglycaemia | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Hyperosmolar hyperglycaemic state | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Hypokalaemia | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Obesity | 2/5846 (0%) | 2 | 1/5847 (0%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Back pain | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Cervical spinal stenosis | 1/5846 (0%) | 2 | 0/5847 (0%) | 0 |
| Intervertebral disc degeneration | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Lumbar spinal stenosis | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Musculoskeletal chest pain | 0/5846 (0%) | 0 | 3/5847 (0.1%) | 3 |
| Osteoarthritis | 1/5846 (0%) | 1 | 1/5847 (0%) | 1 |
| Rotator cuff syndrome | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Spinal osteoarthritis | 0/5846 (0%) | 0 | 2/5847 (0%) | 2 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Astrocytoma malignant | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Breast cancer female | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Colon cancer | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Colorectal adenocarcinoma | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Gastric cancer | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Invasive ductal breast carcinoma | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Ovarian germ cell teratoma benign | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Squamous cell carcinoma | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Uterine leiomyoma | 2/5846 (0%) | 2 | 0/5847 (0%) | 0 |
| Nervous system disorders | ||||
| Cerebral haematoma | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Cerebral infarction | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Cerebrospinal fluid leakage | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Cerebrovascular accident | 0/5846 (0%) | 0 | 3/5847 (0.1%) | 4 |
| Cerebrovascular disorder | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Hypoaesthesia | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Monoparesis | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Seizure | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Syncope | 3/5846 (0.1%) | 3 | 1/5847 (0%) | 1 |
| Pregnancy, puerperium and perinatal conditions | ||||
| Hyperemesis gravidarum | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Psychiatric disorders | ||||
| Aggression | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Bipolar I disorder | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Completed suicide | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Depression | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Stress | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Suicide attempt | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Hydronephrosis | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Nephritis | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Nephrolithiasis | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Pelvi-ureteric obstruction | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Urinary tract infection | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Reproductive system and breast disorders | ||||
| Haemorrhagic ovarian cyst | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Menometrorrhagia | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Ovarian cyst | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Pelvic prolapse | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Uterine haemorrhage | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute respiratory distress syndrome | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Asthma | 35/5846 (0.6%) | 38 | 36/5847 (0.6%) | 39 |
| Cough | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Dyspnoea | 1/5846 (0%) | 1 | 2/5847 (0%) | 2 |
| Pneumonitis | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Respiratory distress | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Rhinitis allergic | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Status asthmaticus | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
| Vocal cord disorder | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Vascular disorders | ||||
| Deep vein thrombosis | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Haematoma | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Hypertension | 0/5846 (0%) | 0 | 1/5847 (0%) | 1 |
| Venous thrombosis limb | 1/5846 (0%) | 1 | 0/5847 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Symbicort | Budesonide | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/5846 (0%) | 0/5847 (0%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
≥ 60 days prior to submission of material for publication/presentation, Institution and PI shall jointly provide AZ with material for review. No publication/presentation may include any of AZ's Confidential Information without AZ's written approval. AZ can request Inst. and PI to withhold material from submission for publication/presentation for an additional 90 days to allow AZ to establish and preserve its proprietary rights in the material being submitted for publication or presentation.
Results Point of Contact
| Name/Title | Carin Jorup, Global Clinical Lead (GCL) SYMBICORT |
|---|---|
| Organization | AstraZeneca Research and Development |
| Phone | +46 31 7761000 |
| Carin.Jorup@astrazeneca.com |
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01444430
Other Study ID Numbers:
- D5896C00027
- 2011-002790-28
First Posted:
Sep 30, 2011
Last Update Posted:
Dec 15, 2016
Last Verified:
Nov 1, 2016