Comparison of Indacaterol 150 mcg Once Daily (o.d.) With Salmeterol/Fluticasone Propionate 50 mcg/500 mcg Twice Daily (b.i.d.) (INSTEAD)
|ClinicalTrials.gov Identifier: NCT01555138|
Recruitment Status : Completed
First Posted : March 15, 2012
Results First Posted : April 28, 2015
Last Update Posted : April 28, 2015
|Condition or disease||Intervention/treatment||Phase|
|Chronic Obstructive Pulmonary Disease||Drug: Indacaterol Drug: Salmeterol||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||581 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Randomized, Double-blind, Parallel-group, 26-week Study Comparing the Efficacy and Safety of Indacaterol (Onbrez® Breezhaler® 150 mcg o.d.) With Salmeterol/Fluticasone Propionate (Seretide® Accuhaler® 50 mcg/500 mcg b.i.d.) in Patients With Moderate Chronic Obstructive Pulmonary Disease|
|Study Start Date :||February 2012|
|Actual Primary Completion Date :||February 2014|
|Actual Study Completion Date :||February 2014|
Indacaterol 150 mcg once daily (o.d.) delivered via the Novartis single dose dry power inhaler (SDDPI) (Onbrez® Breezhaler®)
Indacaterol is delivered via a SDDPI.
Active Comparator: Salmeterol/fluticasone propionate
Salmeterol 50 mcg /fluticasone propionate 500 mcg for inhalation delivered via a proprietary multi dose dry powder inhaler (MDDPI) device (Seretide® Accuhaler®) twice daily (b.i.d.)
Salmeterol/fluticasone is delivered via a MDDPI
- Trough Forced Expiratory Volume in One Second (FEV1) at 12 Weeks (Imputed With LOCF): Treatment Comparisons [ Time Frame: 12 weeks ]Spirometry conducted to internationally accepted standards. Trough FEV1 defined as the mean of the FEV1 measurements at 23 h 10 min and 23 h 45 min post the Day 84 morning dose. The primary variable (imputed with last observation carried forward) will be analysed using a mixed model for the Per Protocol Set (PPS). The model will contain treatment as a fixed effect with the baseline FEV1 measurement, FEV1 prior to inhalation and FEV1 10-15 min post inhalation of salbutamol (components of reversibility at Visit 1) as covariates.
- Trough FEV1 (L) at Week 26 (Imputed With LOCF): Treatment Comparisons [ Time Frame: 26 weeks ]Trough FEV1 is defined as the average of the 23 h 10 min and the 23 h 45 min values taken in the clinic at Visit 11.
- FEV1 (L) at Individual Time Points After 12 Weeks Treatment: Treatment Comparisons [ Time Frame: 12 weeks ]FEV1 at each time point, for each visit, will be analyzed using the same mixed model as specified for the primary analysis. Least squares means will be displayed by treatment group.
- FEV1 (L) at Individual Time Points After 26 Weeks Treatment: Treatment Comparisons [ Time Frame: 26 weeks ]FEV1 at each time point, for each visit, will be analyzed using the same mixed model as specified for the primary analysis. Least squares means will be displayed by treatment group .
- FVC Over 26 Weeks of Treatment [ Time Frame: 12 and 26 weeks ]FVC at each time point, for each visit, will be analyzed using the same mixed model as specified for the primary analysis. Least squares means will be displayed by treatment group.
- Analysis of AUC (5 Min - 4 h) for FEV1 (L) at Week 12 and Week 26: Treatment Comparison [ Time Frame: 12 and 26 weeks ]The standardized (with respect to the length of time) AUC for FEV1 will be calculated between 5 min and 4 h post morning dose as the sum of trapezoids divided by the length of time at Day 84 (Visit 6) and Day 182 (Visit 10). Scheduled (not actual) time points are to be used. FEV1 measurements taken within 6 h of rescue use will be set to missing before the standardized AUC is calculated.
- TDI Focal Score at Week 12 and Week 26: Treatment Comparisons [ Time Frame: 12 and 26 weeks ]The Transition Dyspnea Index (TDI) total score after 12 and 26 weeks of treatment will be analyzed using the same mixed model as specified for the primary analysis with the Baseline Dyspnea Index (BDI) total score as the baseline.Total score ranging - 9 to + 9. The lower the score, the more deterioration in severity of dyspnea. One additional option in each category, which does not contribute to the score, allows for circumstances in which impairment is due to reasons other than dyspnea.
- Number of COPD Exacerbations Per Patient Over 26 Weeks: Treatment Comparisons (Without Imputation; Full Analysis Set) [ Time Frame: 26 weeks ]The number of exacerbations during the 26 week treatment period will be analyzed using a generalized linear model assuming a negative binomial distribution.
- Mean Daily Number of Puffs of Rescue Medication Used Over 26 Weeks of Treatment [ Time Frame: 12 and 26 weeks ]The mean daily number of puffs of rescue medication taken by the patient will be derived. If the number of puffs is missing for part of the day (either morning or evening) then a half day will be used in the denominator. Rescue medication data recorded during the 14 day run-in period will be used to calculate the baseline. The mean change from baseline in the daily number of puffs of rescue medication will be analyzed using the same mixed model as specified for the primary analysis, with the baseline FEV1 replaced with the baseline daily rescue use.
- Rescue Medication Use Over 26 Weeks: Percentage of 'Days With no Rescue Use' [ Time Frame: 26 weeks ]A 'day with no rescue use' is defined from diary data as any day where the patient has taken no puffs of rescue medication. The percentage of 'days with no rescue use' will be derived and analyzed as for the percentage of 'nights with no nighttime awakenings'.
- St Georges Respiratory Questionnaire for COPD [ Time Frame: 12 and 26 weeks ]A Total and three component scores are calculated: Symptoms; Activity; Impacts. Each component of the questionnaire is scored separately:The score for each component is calculated separately by dividing the summed weights by the maximum possible weight for that component and expressing the result as a percentage: Score = 100 x Summed weights from all positive items in that component divided by Sum of weights for all items in that component The Total score is calculated in similar way: Score = 100 x Summed weights from all positive items in the questionnaire divided by Sum of weights for all items in the questionnaire Sum of maximum possible weights for each component and Total: Symptoms 566.2 Activity 982.9 Impacts 1652.8 Total (sum of maximum for all three components) 3201.9 The proportion of patients who achieve a clinically important improvement of at least 4 units in the total SGRQ will be analyzed. The higher the score the more symptoms of disease are present.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01555138
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|Study Director:||Novartis Pharmaceuticals||Novartis Pharmaceuticals|