Comparing the Efficacy of Symbicort® pMDI and Formoterol Turbuhaler in Reducing Exacerbations in Patients With Cronic Obstructive Pulmonary Disease (RISE)
|COPD Patients||Drug: Symbicort Drug: Formoterol turbohaler Other: Placebo for Symbicort pMDI Other: Placebo for Formoterol Turbohaler||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
|Official Title:||A Phase IIIB, 6-Month, Double-blind, Double-dummy, Randomized, Parallel-group, Multicenter Exacerbation Study of Symbicort® Pressurized Metered-Dose Inhaler (pMDI) 160/4.5 μg x 2 Actuations Twice-daily Compared to Formoterol Turbuhaler 4.5 μg x 2 Inhalations Twice-daily in Cronic Obstructive Pulmonary Disease (COPD) Patients.|
- The Rate of Moderate and Severe COPD Exacerbations Defined as: Worsening of ≥2 Major Symptoms or Worsening of 1 Major Symptom Together With ≥1 Minor Symptom for ≥2 Consecutive Days [ Time Frame: Randomization at Week 0 to End of Treatment (EoT) W 26 ]
The annual COPD exacerbation rate was analyzed and compared between two arms.
Annual exacerbation rate for each subject is defined as number of exacerbations divided by duration of randomized treatment period in years.
The annual COPD exacerbation rate of Symbicort group was compared with annual rate of Formoterol group. The rate ratio of Symbicort vs. Formoteroal was assessed by a negative binomial model.
Exacerbations, that met the modified Anthonisen criteria and duration ≥2 days were classified as moderate and severe exacerbations.
Moderate exacerbation: treatment of symptoms with systemic corticosteroids (≥3 days) and/or antibiotics.
Severe exacerbation: symptoms that require hospitalization (including >24 hours in ED/urgent care setting).
- Number of Patients With Moderate or Severe COPD Exacerbation. [ Time Frame: From randomzation to EoT W 26 ]
The number of patients who developed moderate or severe COPD exacerbation during treatment period were reported. Cox proportional hazards regression model was fitted to data to compare the two treatment arms .
The hazard ratio and 95% CI were estimated.
- St. George's Respiratory Questionnaire (SGRQ) [ Time Frame: From Run-in W -4 to EoT W 26 ]
SGRQ is a standardized, self-administered tool for measuring impaired health and perceived wellbeing in respiratory diseases; a validated electronic version of the questionnaire in the relevant validated languages was used in this study.
The questionnaire contains 50 items divided into three dimensions (Symptoms, Activity and Impact).
Each of the three dimensions of the questionnaire is scored separately in the range from 0 to 100:
zero (0) score indicating no impairment of quality of life.
The total SGRQ score ranging from 0 to 100 is a summary score utilizing responses to all items calculated using weights attached to each item of the questionnaire.
Higher scores indicate poorer health and change of 4 units in the SGRQ has been determined to be the threshold for a clinically relevant change in health status.
The change from baseline was statistically summarized and compared between two arms in a mixed model.
- Pre-dose/Pre-bronchodilator FEV1 at the Study Site [ Time Frame: From Run-in W -4 to EoT W 26 ]FEV1 from pre-dose spirometry is a measurement of lung function. The change from baseline on pre-dose FEV1 was summarized and compared between Symbicort and Formoterol groups using a mixed model.
- Total Rescue Medication Use (Average Puffs/Day) [ Time Frame: From Run-in W -4 to EoT W 26 ]
Use of rescue medication is a measure of symptoms that need to be treated with a short-acting bronchodilator.
The average daily use across the observation period was used for analysis. Change from baseline was summarized and compared between two arms using a mixed model.
- Nights With Awakening Due to COPD [ Time Frame: From Run-in W -4 to EoT W 26 ]
Nighttime awakening due to COPD symptoms correspond to the severity of nocturnal symptoms from COPD.
The average number of awakening per night over the treatment period was analyzed. It was derived as the number of night with awakening divided by the total number of nights with data in the recording period. Change from baseline period on awakening was summarized and compared between two arms using a mixed model.
|Actual Study Start Date:||June 27, 2014|
|Study Completion Date:||February 8, 2016|
|Primary Completion Date:||February 8, 2016 (Final data collection date for primary outcome measure)|
Active Comparator: Symbicort pMDI
Symbicort pMDI, budesonide/formoterol, 160/4.5 μg x 2 actuations BID, for oral inhalation
Budesonide/formoterol pMDI, 160/4.5 μg x 2 actuations BID, for oral inhalation, 120 dosesOther: Placebo for Symbicort pMDI
pMDI, aerosol for oral inhalation, placebo, 120 doses
Active Comparator: Formoterol Turbuhaler
Formoterol Turbuhaler, 4.5 μg x 2 actuations BID, for oral inhalation
Drug: Formoterol turbohaler
Formoterol Turbuhaler 4.5 μg x 2 actuations BID, for oral inhalation, 60 dosesOther: Placebo for Formoterol Turbohaler
PLacebo powder for oral inhalation, 60 doses
Please refer to this study by its ClinicalTrials.gov identifier: NCT02157935
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|Principal Investigator:||Gary T Ferguson, MD||Pulmonary Research Insititute of Southeast Michigan|