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Trial record 38 of 318 for:    FLUTICASONE AND SALMETEROL

Study to Evaluate Efficacy/Safety of Combination Budesonide/Indacaterol vs Fluticasone/Salmeterol in Patients With COPD (COMBINE)

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ClinicalTrials.gov Identifier: NCT02055352
Recruitment Status : Completed
First Posted : February 5, 2014
Results First Posted : April 18, 2017
Last Update Posted : April 18, 2017
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Chronic Obstructive Pulmonary Disease
Interventions Drug: Budesonide
Drug: Fluticasone
Drug: Indacaterol
Drug: Salmeterol
Enrollment 222
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Budesonide/Indacaterol Fluticasone / Salmeterol
Hide Arm/Group Description Participants will receive a fixed combination of fluticasone and salmeterol during 4 weeks followed by a free combination of budesonide and indacaterol for the remainig of study. Fixed combination of fluticasone and salmeterol
Period Title: Overall Study
Started 109 113
Per-Protocol Set (PPS) 108 111
Completed 103 96
Not Completed 6 17
Reason Not Completed
Adverse Event             0             1
Non-eligible             0             1
Poor compliance             1             1
Death             1             2
Patient decision             1             1
Use of prohibited treatment             0             3
AE, study drug would be detrimental             1             3
Withdrawal of informed consent             1             0
Reason unknown             1             5
Arm/Group Title Budesonide/Indacaterol Fluticasone / Salmeterol Total
Hide Arm/Group Description Participants will receive a fixed combination of fluticasone and salmeterol during 4 weeks followed by a free combination of budesonide and indacaterol for the remainig of study. Fixed combination of fluticasone and salmeterol Total of all reporting groups
Overall Number of Baseline Participants 109 113 222
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 109 participants 113 participants 222 participants
67.1  (9) 67.3  (8.45) 67.2  (8.70)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 109 participants 113 participants 222 participants
Female
41
  37.6%
54
  47.8%
95
  42.8%
Male
68
  62.4%
59
  52.2%
127
  57.2%
1.Primary Outcome
Title Change From Baseline in Trough Forced Expiratory Volume in 1 Second (Non-inferiority Analysis).
Hide Description Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation.
Time Frame Baseline and week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol set (PPS) included all patients in the FAS without any major protocol deviations. Major protocol deviations were defined in the validation analysis plan prior to database lock and the unblinding of the study. Patients were analyzed according to the treatment they are randomized to
Arm/Group Title Budesonide/Indacaterol Fluticasone / Salmeterol
Hide Arm/Group Description:
Participants will receive a fixed combination of fluticasone and salmeterol during 4 weeks followed by a free combination of budesonide and indacaterol for the remainig of study.
Fixed combination of fluticasone and salmeterol
Overall Number of Participants Analyzed 108 111
Least Squares Mean (Standard Error)
Unit of Measure: Liters
0.080  (0.027) 0.019  (0.028)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Budesonide/Indacaterol, Fluticasone / Salmeterol
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments A change of 5-10% from baseline values is considered to be clinically important. The estimated adjusted treatment difference for budesonide 400 μg twice a day/ indacaterol 150 μg once daily minus fixed combination of fluticasone/ salmeterol 250/ 50 μg twice daily was displayed along with the associated one-sided 97.5% confidence interval. If the lower limit of this confidence interval was to the right (i.e. above) – 10 mL, then non-inferiority could be claimed.
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Mixed effects General linear model
Comments [Not Specified]
2.Secondary Outcome
Title Change in Health Status - mMRC
Hide Description Modified Medical Research Council scale (mMRC) questionnaire will be completed by participants. 0 Not troubled with breathlessness except with strenuous exercise; 1 Troubled by shortness of breath when hurrying on the level or walking up a slight hill; 2 Walks slower than people of the same age on the level because of breathlessness or has to stop for breath when walking at own pace on the level; 3 Stops for breath after walking about 100 yards or after a few minutes on the level; 4 Too breathless to leave the house or breathless when dressing or undressing
Time Frame Baseline, week 12 and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol set (PPS) included all patients in the FAS without any major protocol deviations. Major protocol deviations were defined in the validation analysis plan prior to database lock and the unblinding of the study. Patients were analyzed according to the treatment they are randomized to
Arm/Group Title Budesonide/Indacaterol Fluticasone / Salmeterol
Hide Arm/Group Description:
Participants will receive a fixed combination of fluticasone and salmeterol during 4 weeks followed by a free combination of budesonide and indacaterol for the remainig of study.
Fixed combination of fluticasone and salmeterol
Overall Number of Participants Analyzed 108 111
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
Week 12 1.452  (0.111) 1.623  (0.113)
Week 24 1.315  (0.112) 1.414  (0.115)
3.Secondary Outcome
Title Change From Baseline in Mean Daily Number of Puffs of Rescue Medication Used Over the 24 Week Treatment
Hide Description A day with no rescue medication use is defined from the diary data as any day where the patient recorded no rescue medicine use during the previous 12 hours.
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol set (PPS) included all patients in the FAS without any major protocol deviations. Major protocol deviations were defined in the validation analysis plan prior to database lock and the unblinding of the study. Patients that were not discontinued before Visit 3 (day 28±3).
Arm/Group Title Budesonide/Indacaterol Fluticasone / Salmeterol
Hide Arm/Group Description:
Participants will receive a fixed combination of fluticasone and salmeterol during 4 weeks followed by a free combination of budesonide and indacaterol for the remainig of study.
Fixed combination of fluticasone and salmeterol
Overall Number of Participants Analyzed 105 105
Mean (Standard Deviation)
Unit of Measure: Puffs
10.5  (9.53) 12.9  (12.34)
4.Secondary Outcome
Title Change From Baseline in Trough Forced Expiratory Volume in 1 Second at Week 24 (Analysis of Superiority)
Hide Description Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing.
Time Frame Baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol set (PPS) included all patients in the FAS without any major protocol deviations. Major protocol deviations were defined in the validation analysis plan prior to database lock and the unblinding of the study. Patients were analyzed according to the treatment they are randomized to
Arm/Group Title Budesonide/Indacaterol Fluticasone / Salmeterol
Hide Arm/Group Description:
Participants will receive a fixed combination of fluticasone and salmeterol during 4 weeks followed by a free combination of budesonide and indacaterol for the remainig of study.
Fixed combination of fluticasone and salmeterol
Overall Number of Participants Analyzed 108 111
Least Squares Mean (Standard Error)
Unit of Measure: Liters
0.063  (0.033) 0.020  (0.034)
5.Secondary Outcome
Title Change in Health Status - SGRQ-C
Hide Description St George’s Respiratory Questionnaire short version questionnaire will be completed by participants. The SGRQ ranges from 0 (no impairment of quality of life) to 100 (highest impairment of quality of life)
Time Frame Baseline, week 12 and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol set (PPS) included all patients in the FAS without any major protocol deviations. Major protocol deviations were defined in the validation analysis plan prior to database lock and the unblinding of the study. Patients were analyzed according to the treatment they are randomized to
Arm/Group Title Budesonide/Indacaterol Fluticasone / Salmeterol
Hide Arm/Group Description:
Participants will receive a fixed combination of fluticasone and salmeterol during 4 weeks followed by a free combination of budesonide and indacaterol for the remainig of study.
Fixed combination of fluticasone and salmeterol
Overall Number of Participants Analyzed 108 111
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
Week 12 -8.703  (2.006) -2.334  (2.053)
Week 24 -7.787  (2.308) -2.523  (2.384)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Budesonide / Indacaterol (A) Fluticasone / Salmeterol (B)
Hide Arm/Group Description Budesonide / Indacaterol (A) Fluticasone / Salmeterol (B)
All-Cause Mortality
Budesonide / Indacaterol (A) Fluticasone / Salmeterol (B)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Budesonide / Indacaterol (A) Fluticasone / Salmeterol (B)
Affected / at Risk (%) Affected / at Risk (%)
Total   10/109 (9.17%)   9/113 (7.96%) 
Cardiac disorders     
Acute myocardial infarction  1  0/109 (0.00%)  1/113 (0.88%) 
Bradycardia  1  0/109 (0.00%)  1/113 (0.88%) 
Cor pulmonale  1  0/109 (0.00%)  1/113 (0.88%) 
Nodal arrhythmia  1  0/109 (0.00%)  1/113 (0.88%) 
Infections and infestations     
Cellulitis  1  0/109 (0.00%)  1/113 (0.88%) 
Pneumonia  1  3/109 (2.75%)  1/113 (0.88%) 
Injury, poisoning and procedural complications     
Hip fracture  1  0/109 (0.00%)  1/113 (0.88%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Bronchial carcinoma  1  1/109 (0.92%)  0/113 (0.00%) 
Hepatocellular carcinoma  1  0/109 (0.00%)  1/113 (0.88%) 
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema  1  0/109 (0.00%)  1/113 (0.88%) 
Chronic obstructive pulmonary disease  1  6/109 (5.50%)  2/113 (1.77%) 
Haemoptysis  1  1/109 (0.92%)  0/113 (0.00%) 
Pulmonary embolism  1  1/109 (0.92%)  0/113 (0.00%) 
Vascular disorders     
Peripheral arterial occlusive disease  1  0/109 (0.00%)  1/113 (0.88%) 
Vascular insufficiency  1  0/109 (0.00%)  1/113 (0.88%) 
Venous thrombosis limb  1  0/109 (0.00%)  1/113 (0.88%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Budesonide / Indacaterol (A) Fluticasone / Salmeterol (B)
Affected / at Risk (%) Affected / at Risk (%)
Total   24/109 (22.02%)   39/113 (34.51%) 
Infections and infestations     
Influenza  1  6/109 (5.50%)  10/113 (8.85%) 
Nasopharyngitis  1  11/109 (10.09%)  10/113 (8.85%) 
Urinary tract infection  1  3/109 (2.75%)  7/113 (6.19%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/109 (0.92%)  7/113 (6.19%) 
Back pain  1  1/109 (0.92%)  6/113 (5.31%) 
Nervous system disorders     
Headache  1  1/109 (0.92%)  9/113 (7.96%) 
Respiratory, thoracic and mediastinal disorders     
Dysphonia  1  3/109 (2.75%)  8/113 (7.08%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02055352     History of Changes
Other Study ID Numbers: CQAB149BAR01
First Submitted: February 3, 2014
First Posted: February 5, 2014
Results First Submitted: January 25, 2017
Results First Posted: April 18, 2017
Last Update Posted: April 18, 2017