Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD,, QVA149,, Tiotropium,, FDC,, GlycOpyrronium With IndacatERol,, POWER
Brief summary
This is a single cohort, prospective post approval study conducted on patients with COPD in Canada. The study will enroll patients that have not responded to their current treatment of tiotropium alone, or who are on the fixed dose combinations fluticasone propionate/salmeterol. Only patients for whom the physician has decided to change treatment due to lack of efficacy will be eligible to be enrolled in the study. Also will evaluate the real-life effectiveness of QVA149 (indacaterol 110 mcg/glycopyrronium 50 mcg) in the management of patients.
Interventions
DRUGGlycopyrronium /Indacaterol maleate
Glycopyrronium 50mcg/Indacaterol maleate 110mcg once daily by a breezhaler device
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient diagnosed and treated for moderate to severe COPD according to the Global Initiative for Chronic Obstructive Lung Disease according to physician's assessment * Smoking history of \> 10 pack - years. * On-going treatment with tiotropium or fixed dose combination of LABA/ICS, specifically combinations fluticasone propionate/salmeterol for a minimum of three months but demonstrating persistence of symptoms indicating change of treatment to combination therapy \*\*using a CAT score \> 10. * Treatment with QVA149 is indicated as per the product monograph and appropriate for the patient as per the judgment of the treating physician. * Patient has signed informed consent agreeing to participate in the study and undergo the study treatments and allowing the use of their data for the purposes of the study. * Patient is expected to be available for 16 weeks after study enrolment * Assessed as per routine care or as documented in the patient's chart. \*\* As determined and decided by the treating physician prior to enrolment of the patient in the study.
Exclusion criteria
Patients fulfilling any of the following criteria are not eligible for inclusion in this study. No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible patients. * Patients not willing to sign an informed consent. * Patient on maintenance treatment including triple therapy (LABA +LAMA+ICS) for COPD * Patients with a diagnosis of asthma or history of asthma. * Patients who have had two or more moderate to severe exacerbations during the last 12 months prior to study enrolment. A moderate COPD exacerbation is defined by requirement for treatment with systemic corticosteroids or antibiotics or both. A severe COPD exacerbation is defined by hospitalization, including an emergency room visit of longer than 24 h. * Patients who had an exacerbation within the previous 6 weeks to enrolment. * Patients who as per physician clinical judgment will require ICS treatment co-administered with QVA149 during the study period. * Patients with other chronic respiratory conditions that may affect the outcome of treatment including but not limited to lung cancer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Trough (Forced Expiratory Volume (FEV1) (Pre-dose FEV1) | 16 weeks study | Primary end points: To evaluate the real-life effectiveness of QVA149 (indacaterol 110 mcg/glycopyrronium 50 mcg) in the management of patients with COPD who have symptoms defined as CAT score \>10 with tiotropium monotherapy; effectiveness will be assessed as the mean change in trough FEV1 from baseline to 16 weeks. and to evaluate the real-life effectiveness of QVA149 (indacaterol 110 mcg/glycopyrronium 50 mcg) in the management of patients with COPD who have symptoms defined as CAT score \>10 while on treatment with FDC of fluticasone propionate/salmeterol; effectiveness will be assessed as the mean change in trough FEV1 from baseline to 16 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Trough FEV1 (Forced Expiratory Volume) to Week 4 | Baseline, week 4 | Portable spirometers will be provided to investigators and they will use this device for all of their patient measurements of FEV1 during the trial |
| Single Point and Change in Baseline Dyspnea Index and Transitional Dyspnea Index (BDI/TDI) | Baseline, Week 4, week 16 | A trained assessor interviewed the patient and graded the degree of impairment due to dyspnea (difficulty breathing). BDI/TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort and captures changes from baseline. BDI was measured at day 1 prior to the first dose with domain scores ranging from 0=very severe to 4=no impairment and a total score ranging from 0 to 12(best). TDI captures changes from baseline. Each domain is scored from -3=major deterioration to 3=major improvement to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score. The BDI was assessed at Baseline, whereas the TDI was assessed at Week 4 and Week 16. |
| Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Questionnaire (CAT) | Baseline, week 4, week 16 | The CAT is an 8 item questionnaire that assesses the impact of COPD on the patient's functional status. Scores for each of the 8 items are summed to give an overall score (out of 40). The score ranges from 0-40 where higher scores represent worse health status. CAT scores ≥ 10 are associated with significantly impaired health status. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ULTIBRO BREEZHALER Patients diagnosed with chronic obstructive pulmonary disorder (COPD) who are symptomatic (CAT score over 10) and who are treated with Tiotropium (SPIRIVA HANDALER) or Fluticasone propionate/Salmeterol- ADVAIR DISKUS (FDC). | 338 |
| Total | 338 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Abnormal test procedure result | 1 |
| Overall Study | Administrative problems | 6 |
| Overall Study | Adverse Event | 32 |
| Overall Study | Lost to Follow-up | 6 |
| Overall Study | Patient withdrew consent | 12 |
| Overall Study | Protocol deviation | 18 |
| Overall Study | Screen failed | 24 |
| Overall Study | Unsatisfactory therapeutic effect | 1 |
Baseline characteristics
| Characteristic | ULTIBRO BREEZHALER |
|---|---|
| Age, Continuous | 66.1 Years STANDARD_DEVIATION 9.46 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 330 Participants |
| Sex: Female, Male Female | 149 Participants |
| Sex: Female, Male Male | 189 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 373 |
| other Total, other adverse events | 56 / 373 |
| serious Total, serious adverse events | 12 / 373 |
Outcome results
Primary
Change From Baseline in Trough (Forced Expiratory Volume (FEV1) (Pre-dose FEV1)
Primary end points: To evaluate the real-life effectiveness of QVA149 (indacaterol 110 mcg/glycopyrronium 50 mcg) in the management of patients with COPD who have symptoms defined as CAT score \>10 with tiotropium monotherapy; effectiveness will be assessed as the mean change in trough FEV1 from baseline to 16 weeks. and to evaluate the real-life effectiveness of QVA149 (indacaterol 110 mcg/glycopyrronium 50 mcg) in the management of patients with COPD who have symptoms defined as CAT score \>10 while on treatment with FDC of fluticasone propionate/salmeterol; effectiveness will be assessed as the mean change in trough FEV1 from baseline to 16 weeks.
Time frame: 16 weeks study
Population: Intent to treat set (ITT)- included all patients who received the study treatment and returned for ≥ 1 post baseline visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| QVA149 110/50 After Flu/Sal | Change From Baseline in Trough (Forced Expiratory Volume (FEV1) (Pre-dose FEV1) | 0.17 Liter | Standard Deviation 0.397 |
| QVA149 110/50 After Tio | Change From Baseline in Trough (Forced Expiratory Volume (FEV1) (Pre-dose FEV1) | 0.18 Liter | Standard Deviation 0.321 |
95% CI: [0.14, 0.21]Descriptive Statistics with 95% CI
Secondary
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Questionnaire (CAT)
The CAT is an 8 item questionnaire that assesses the impact of COPD on the patient's functional status. Scores for each of the 8 items are summed to give an overall score (out of 40). The score ranges from 0-40 where higher scores represent worse health status. CAT scores ≥ 10 are associated with significantly impaired health status.
Time frame: Baseline, week 4, week 16
Population: Intent to treat set (ITT)- included all patients who received the study treatment and returned for ≥ 1 post baseline visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QVA149 110/50 After Flu/Sal | Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Questionnaire (CAT) | Week 4 | -5.9 Score | Standard Deviation 7.55 |
| QVA149 110/50 After Flu/Sal | Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Questionnaire (CAT) | Week 16 | -8.2 Score | Standard Deviation 8.34 |
| QVA149 110/50 After Tio | Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Questionnaire (CAT) | Week 4 | -4.7 Score | Standard Deviation 5.71 |
| QVA149 110/50 After Tio | Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Questionnaire (CAT) | Week 16 | -5.9 Score | Standard Deviation 6.44 |
Comparison: Week 495% CI: [-5.7, -4.3]standard descriptive statistics
Comparison: Week 1695% CI: [-7.3, -5.7]standard descriptive statistics
Secondary
Change From Baseline in Trough FEV1 (Forced Expiratory Volume) to Week 4
Portable spirometers will be provided to investigators and they will use this device for all of their patient measurements of FEV1 during the trial
Time frame: Baseline, week 4
Population: Intent to treat set (ITT)- included all patients who received the study treatment and returned for ≥ 1 post baseline visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| QVA149 110/50 After Flu/Sal | Change From Baseline in Trough FEV1 (Forced Expiratory Volume) to Week 4 | 0.12 Liter | Standard Deviation 0.308 |
| QVA149 110/50 After Tio | Change From Baseline in Trough FEV1 (Forced Expiratory Volume) to Week 4 | 0.14 Liter | Standard Deviation 0.267 |
95% CI: [0.11, 0.17]Descriptive Statistics with 95% CI
Secondary
Single Point and Change in Baseline Dyspnea Index and Transitional Dyspnea Index (BDI/TDI)
A trained assessor interviewed the patient and graded the degree of impairment due to dyspnea (difficulty breathing). BDI/TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort and captures changes from baseline. BDI was measured at day 1 prior to the first dose with domain scores ranging from 0=very severe to 4=no impairment and a total score ranging from 0 to 12(best). TDI captures changes from baseline. Each domain is scored from -3=major deterioration to 3=major improvement to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score. The BDI was assessed at Baseline, whereas the TDI was assessed at Week 4 and Week 16.
Time frame: Baseline, Week 4, week 16
Population: Intent to treat set (ITT)- included all patients who received the study treatment and returned for ≥ 1 post baseline visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QVA149 110/50 After Flu/Sal | Single Point and Change in Baseline Dyspnea Index and Transitional Dyspnea Index (BDI/TDI) | BDI week 0 | 6.5 Score | Standard Deviation 2.07 |
| QVA149 110/50 After Flu/Sal | Single Point and Change in Baseline Dyspnea Index and Transitional Dyspnea Index (BDI/TDI) | TDI week 4 | 2.2 Score | Standard Deviation 2.72 |
| QVA149 110/50 After Flu/Sal | Single Point and Change in Baseline Dyspnea Index and Transitional Dyspnea Index (BDI/TDI) | TDI week 16 | 2.9 Score | Standard Deviation 3.28 |
| QVA149 110/50 After Tio | Single Point and Change in Baseline Dyspnea Index and Transitional Dyspnea Index (BDI/TDI) | BDI week 0 | 6.8 Score | Standard Deviation 2.09 |
| QVA149 110/50 After Tio | Single Point and Change in Baseline Dyspnea Index and Transitional Dyspnea Index (BDI/TDI) | TDI week 4 | 2.0 Score | Standard Deviation 2.38 |
| QVA149 110/50 After Tio | Single Point and Change in Baseline Dyspnea Index and Transitional Dyspnea Index (BDI/TDI) | TDI week 16 | 2.4 Score | Standard Deviation 2.78 |
Comparison: Week 495% CI: [1.74, 2.3]Standard Descriptive Statistics
Comparison: Week 1695% CI: [2.21, 2.85]Standard Descriptive Statistics