Prospective Cohort Study for the Real - Life Effectiveness Evaluation of GlycOpyrronium With IndacatERol Combination in the Management of COPD in Canada (POWER Study)

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02202616
• Collaborator: (none)
• Enrollment: 401
• Location: 1
• Arm: 1
• Actual Duration (Months): 31.3
• Patients Per Site Per Month: 12.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: Glycopyrronium /Indacaterol maleate	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 401 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prospective Cohort Study for the Real - Life Effectiveness Evaluation of GlycOpyrronium With IndacatERol Combination in the Management of COPD in Canada (POWER Study)
• Actual Study Start Date: Aug 27, 2014
• Actual Primary Completion Date: Apr 5, 2017
• Actual Study Completion Date: Apr 5, 2017

Arms and Interventions

Arm	Intervention/Treatment
Other: 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).	Drug: Glycopyrronium /Indacaterol maleate; Glycopyrronium 50mcg/Indacaterol maleate 110mcg once daily by a breezhaler device

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

2. 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.

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	St-Charles-Borromée	Quebec	Canada	J6E 2B4

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Jun 3, 2015
• Statistical Analysis Plan - Sep 14, 2017

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02202616
• Other Study ID Numbers: CQVA149ACA01
• First Posted: Jul 29, 2014
• Last Update Posted: Jul 2, 2019
• Last Verified: Jun 1, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: COPD,; QVA149,; Tiotropium,; FDC,; GlycOpyrronium With IndacatERol,; POWER
• Additional relevant MeSH terms: Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Glycopyrrolate

Study Results

Participant Flow

Arm/Group Title	QVA149 110/50
Arm/Group Description	QVA149 110/50- 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).
Period Title: Overall Study
STARTED	401
Intent to Treat Set (ITT)	338
COMPLETED	301
NOT COMPLETED	100

Baseline Characteristics

Arm/Group Title	ULTIBRO BREEZHALER
Arm/Group Description	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).
Overall Participants	338
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	66.1 (9.46)
Sex: Female, Male (Count of Participants)
Female	149 44.1%
Male	189 55.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 0.6%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 0.6%
White	330 97.6%
More than one race	0 0%
Unknown or Not Reported	4 1.2%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Trough (Forced Expiratory Volume (FEV1) (Pre-dose FEV1)
Description	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

Outcome Measure Data

Analysis Population Description

Intent to treat set (ITT)- included all patients who received the study treatment and returned for ≥ 1 post baseline visit

Arm/Group Title	QVA149 110/50 After Flu/Sal	QVA149 110/50 After Tio
Arm/Group Description	QVA149 110/50 combination of (indacaterol maleate 110 µg and glycopyrronium bromide 50 µg) after patients treated with FDC of fluticasone propionate and salmeterol	QVA149 110/50 combination of (indacaterol maleate 110 µg and glycopyrronium bromide 50 µg) after patients treated with tiotropium
Measure Participants	83	235
Mean (Standard Deviation) [Liter]	0.17 (0.397)	0.18 (0.321)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QVA149 110/50 After Flu/Sal, QVA149 110/50 After Tio
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 95%; 0.14 to 0.21
	Parameter Dispersion	Type: Standard Deviation; Value: 0.340
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Trough FEV1 (Forced Expiratory Volume) to Week 4
Description	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

Outcome Measure Data

Analysis Population Description

Intent to treat set (ITT)- included all patients who received the study treatment and returned for ≥ 1 post baseline visit

Arm/Group Title	QVA149 110/50 After Flu/Sal	QVA149 110/50 After Tio
Arm/Group Description	QVA149 110/50 combination of (indacaterol maleate 110 µg and glycopyrronium bromide 50 µg) after patients treated with FDC of fluticasone propionate and salmeterol	QVA149 110/50 combination of (indacaterol maleate 110 µg and glycopyrronium bromide 50 µg) after patients treated with tiotropium
Measure Participants	79	224
Mean (Standard Deviation) [Liter]	0.12 (0.308)	0.14 (0.267)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QVA149 110/50 After Flu/Sal, QVA149 110/50 After Tio
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.14
	Confidence Interval	(2-Sided) 95%; 0.11 to 0.17
	Parameter Dispersion	Type: Standard Deviation; Value: 0.278
	Estimation Comments

3. Secondary Outcome

Title	Single Point and Change in Baseline Dyspnea Index and Transitional Dyspnea Index (BDI/TDI)
Description	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

Outcome Measure Data

Analysis Population Description

Intent to treat set (ITT)- included all patients who received the study treatment and returned for ≥ 1 post baseline visit

Arm/Group Title	QVA149 110/50 After Flu/Sal	QVA149 110/50 After Tio
Arm/Group Description	QVA149 110/50 combination of (indacaterol maleate 110 µg and glycopyrronium bromide 50 µg) after patients treated with FDC of fluticasone propionate and salmeterol	QVA149 110/50 combination of (indacaterol maleate 110 µg and glycopyrronium bromide 50 µg) after patients treated with tiotropium
Measure Participants	87	248
BDI week 0	6.5 (2.07)	6.8 (2.09)
TDI week 4	2.2 (2.72)	2.0 (2.38)
TDI week 16	2.9 (3.28)	2.4 (2.78)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QVA149 110/50 After Flu/Sal, QVA149 110/50 After Tio
	Comments	Week 4
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 95%; 1.74 to 2.30
	Parameter Dispersion	Type: Standard Deviation; Value: 2.47
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	QVA149 110/50 After Flu/Sal, QVA149 110/50 After Tio
	Comments	Week 16
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.5
	Confidence Interval	(2-Sided) 95%; 2.21 to 2.85
	Parameter Dispersion	Type: Standard Deviation; Value: 2.92
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Questionnaire (CAT)
Description	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

Outcome Measure Data

Analysis Population Description

Intent to treat set (ITT)- included all patients who received the study treatment and returned for ≥ 1 post baseline visit

Arm/Group Title	QVA149 110/50 After Flu/Sal	QVA149 110/50 After Tio
Arm/Group Description	QVA149 110/50 combination of (indacaterol maleate 110 µg and glycopyrronium bromide 50 µg) after patients treated with FDC of fluticasone propionate and salmeterol	QVA149 110/50 combination of (indacaterol maleate 110 µg and glycopyrronium bromide 50 µg) after patients treated with tiotropium
Measure Participants	83	234
Week 4	-5.9 (7.55)	-4.7 (5.71)
Week 16	-8.2 (8.34)	-5.9 (6.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QVA149 110/50 After Flu/Sal, QVA149 110/50 After Tio
	Comments	Week 4
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.0
	Confidence Interval	(2-Sided) 95%; -5.7 to -4.3
	Parameter Dispersion	Type: Standard Deviation; Value: 6.25
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	QVA149 110/50 After Flu/Sal, QVA149 110/50 After Tio
	Comments	Week 16
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.5
	Confidence Interval	(2-Sided) 95%; -7.3 to -5.7
	Parameter Dispersion	Type: Standard Deviation; Value: 7.03
	Estimation Comments

Adverse Events

Time Frame	From week 0 to week 16
Arm/Group Title	QVA149 110/50
Arm/Group Description	QVA149 110/50-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).
All Cause Mortality
	QVA149 110/50
	Affected / at Risk (%)	# Events
Total	0/373 (0%)
Serious Adverse Events
	QVA149 110/50
	Affected / at Risk (%)	# Events
Total	12/373 (3.2%)
Blood and lymphatic system disorders
Anaemia	1/373 (0.3%)
Lymphadenopathy mediastinal	1/373 (0.3%)
Cardiac disorders
Cardiac failure	1/373 (0.3%)
Cardiac failure congestive	1/373 (0.3%)
Sinus tachycardia	1/373 (0.3%)
Gastrointestinal disorders
Intestinal ischaemia	1/373 (0.3%)
Infections and infestations
Gastroenteritis	1/373 (0.3%)
Influenza	1/373 (0.3%)
Pneumonia	4/373 (1.1%)
Injury, poisoning and procedural complications
Wound	1/373 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic cancer metastatic	1/373 (0.3%)
Psychiatric disorders
Depression	1/373 (0.3%)
Renal and urinary disorders
Renal failure	1/373 (0.3%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	2/373 (0.5%)
Pleural effusion	1/373 (0.3%)
Pulmonary mass	1/373 (0.3%)
Other (Not Including Serious) Adverse Events
	QVA149 110/50
	Affected / at Risk (%)	# Events
Total	56/373 (15%)
Gastrointestinal disorders
Dyspepsia	4/373 (1.1%)
Nausea	4/373 (1.1%)
Infections and infestations
Bronchitis	9/373 (2.4%)
Upper respiratory tract infection	11/373 (2.9%)
Nervous system disorders
Dizziness	4/373 (1.1%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	13/373 (3.5%)
Cough	10/373 (2.7%)
Dyspnoea	7/373 (1.9%)
Vascular disorders
Hypertension	4/373 (1.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.