Vahelva Respimat Regulatory Post-marketing Surveillance in Korean Patients With Chronic Obstructive Pulmonary Disease

A Regulatory Required Non Interventional Study to Monitor the Safety and Effectiveness of Once Daily Treatment of Orally Inhaled Vahelva Respimat (Tiotropium + Olodaterol Fixed Dose Combination 2.5µg/2.5µg Per Puff (2 Puffs Comprise One Medicinal Dose)) for Korean Patients With COPD (Chronic Obstructive Pulmonary Disease)

To monitor the safety profile and effectiveness of Vahelva Respimat in Korean patients with COPD in a routine clinical practice setting

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination)

Detailed Description

Study Design:

regulatory PMS study

• Study Type: Observational
• Enrollment (Actual): 3223

Contacts and Locations

Study Locations

• Korea, Republic of
  • One Or Multiple Sites, Korea, Republic of, 61469
    • Chonnam National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Korean patients with COPD

Description

Inclusion criteria:

• Patients who have been started on Vahelva Respimat in accordance with the approved label in Korea
• Age >= 18 years at enrolment
• Patients who have signed on the data release consent form

Exclusion criteria:

• Patients with hypersensitivity to Vahelva Respimat or to any of the excipients.
• Patients with a history of hypersensitivity to atropine or its derivatives(e.g. ipratropium, oxitropium, glycopyrronium, clidinium, umeclidinium)
• Patients with asthma
• Current participation in other clinical trials

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination); Korean patients with COPD who are newly prescribed with Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination).	Drug: Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination); The recommended dose for adults is 5 microgram Tiotropium and 5 microgram Olodaterol given as two puffs from the Respimat® inhaler once daily at the same time of the day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Any Adverse Event, Unexpected Adverse Event, Unexpected Serious Adverse Event, Adverse Event Leading to Discontinuation	An adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An adverse event could therefore be any unfavourable and unintended sign (e.g. an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An adverse event was assessed as unexpected if not listed in Local Product Information (LPI) and Company Core Data Sheet (CCDS). Percentage of subjects with any Adverse Event, unexpected Adverse Event, unexpected Serious Adverse Event, Adverse Event leading to discontinuation is reported. Percentages were rounded to two decimal places.	From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of Vahelva® Respimat®, up to 52 (±2) weeks+ 28 days.
Percentage of Subjects With Any Adverse Drug Reaction, Serious Adverse Drug Reaction, Unexpected Adverse Drug Reaction, Unexpected Serious Adverse Drug Reaction, Adverse Drug Reaction Leading to Discontinuation	An adverse drug reaction (ADR) was defined as a response to a medicinal product which is noxious and unintended. Response in this context means that a causal relationship between a medicinal product and an adverse event is at least a reasonable possibility. Adverse reactions may arise from use of the product within or outside the terms of the marketing authorization or from occupational exposure. Conditions of use outside the marketing authorization include off label use, overdose, misuse, abuse and medication errors. Investigator was primarily responsible to assess ADR relatedness. An ADR was assessed as unexpected if not listed in Local Product Information (LPI) and Company Core Data Sheet (CCDS). Percentage of subjects with any Adverse Drug Reaction, serious Adverse Drug Reaction, unexpected Adverse Drug Reaction, unexpected Serious Adverse Drug Reaction, Adverse Drug Reaction leading to discontinuation is reported. Percentages were rounded to two decimal places.	From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of Vahelva® Respimat®, up to 52 (±2) weeks+ 28 days.
Percentage of Subjects With Any Adverse Event (AE) in the Long-term Safety Analysis Set	An adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An adverse event could therefore be any unfavourable and unintended sign (e.g. an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Percentage of participants with any AE is reported. Percentages were rounded to two decimal places.	From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of Vahelva® Respimat®, up to 52 (±2) weeks+ 28 days.
Change From Baseline in Pre-dose Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 24 in the Effectiveness Analysis Set	FEV1 is the maximum amount of air that can be forcefully exhaled in one second. It assesses the degree of airway obstruction in a routine test called spirometry, via a spirometer. FEVI was measured before the administration of Vahelva® Respimat® (pre-dose FEV1) at baseline and at Week 24 (±2 weeks). Pre-dose percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.). Change from baseline in pre-dose percent predicted FEV1 to Week 24 was calculated as: pre-dose percent predicted FEV1 value at Week 24 (±2 weeks) - pre-dose percent predicted FEV1 value at baseline.	At baseline (30 days before baseline visit (Visit 1)) and Week 24 (±2 weeks).
Change From Baseline in Pre-dose Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 52 in the Effectiveness Analysis Set	FEV1 is the maximum amount of air that can be forcefully exhaled in one second. It assesses the degree of airway obstruction in a routine test called spirometry, via a spirometer. FEVI was measured before the administration of Vahelva® Respimat® (pre-dose FEV1) at baseline and at Week 52 (±2 weeks). Pre-dose percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.). Change from baseline in pre-dose percent predicted Forced Expiratory Volume in one second (FEV1) to Week 52 was calculated as: pre-dose percent predicted FEV1 value at Week 52 (±2 weeks) - pre-dose percent predicted FEV1 value at baseline.	At baseline (30 days before baseline visit (Visit 1)) and Week 52 (±2 weeks).
Change From Baseline in Pre-dose Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 24 in the Long-term Effectiveness Analysis Set	FEV1 is the maximum amount of air that can be forcefully exhaled in one second. It assesses the degree of airway obstruction in a routine test called spirometry, via a spirometer. FEVI was measured before the administration of Vahelva® Respimat® (pre-dose FEV1) at baseline and at Week 24 (±2 weeks). Pre-dose percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.). Change from baseline in pre-dose percent predicted Forced Expiratory Volume in one second (FEV1) to Week 24 was calculated as: pre-dose percent predicted FEV1 value at Week 24 (±2 weeks) - pre-dose percent predicted FEV1 value at baseline.	At baseline (30 days before baseline visit (Visit 1)) and Week 24 (±2 weeks).
Change From Baseline in Pre-dose Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 52 in the Long-term Effectiveness Analysis Set	FEV1 is the maximum amount of air that can be forcefully exhaled in one second. It assesses the degree of airway obstruction in a routine test called spirometry, via a spirometer. FEVI was measured before the administration of Vahelva® Respimat® (pre-dose FEV1) at baseline and at Week 52 (±2 weeks). Pre-dose percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.). Change from baseline in pre-dose percent predicted Forced Expiratory Volume in one second (FEV1) to Week 52 was calculated as: pre-dose percent predicted FEV1 value at Week 52 (±2 weeks) - pre-dose percent predicted FEV1 value at baseline.	At baseline (30 days before baseline visit (Visit 1)) and Week 52 (±2 weeks).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Post Bronchodilator Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 24 in the Effectiveness Analysis Set	FEV1 is the maximum amount of air that can be forcefully exhaled in one second. FEVI was measured via a spirometer after the administration of the bronchodilator (Vahelva® Respimat®) at baseline and at Week 24 (±2 weeks). Post bronchodilator percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.). Change from baseline in post bronchodilator percent predicted FEV1 to Week 24 was calculated as: post bronchodilator percent predicted FEV1 value at Week 24 (±2 weeks) - post bronchodilator percent predicted FEV1 value at baseline.	At baseline and Week 24 (±2 weeks).
Change From Baseline in Post Bronchodilator Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 52 in the Effectiveness Analysis Set	FEV1 is the maximum amount of air that can be forcefully exhaled in one second. FEVI was measured via a spirometer after the administration of the bronchodilator (Vahelva® Respimat®) at baseline and at Week 52 (±2 weeks). Post bronchodilator percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.). Change from baseline in post bronchodilator percent predicted FEV1 to Week 52 was calculated as: post bronchodilator percent predicted FEV1 value at Week 52 (±2 weeks) - post bronchodilator percent predicted FEV1 value at baseline.	At baseline and Week 52 (±2 weeks).
Change From Baseline in Post Bronchodilator Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 24 in the Long-term Effectiveness Analysis Set	FEV1 is the maximum amount of air that can be forcefully exhaled in one second. FEVI was measured via a spirometer after the administration of the bronchodilator (Vahelva® Respimat®) at baseline and at Week 24 (±2 weeks). Post bronchodilator percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.). Change from baseline in post bronchodilator percent predicted FEV1 to Week 24 was calculated as: post bronchodilator percent predicted FEV1 value at Week 24 (±2 weeks) - post bronchodilator percent predicted FEV1 value at baseline.	At baseline and Week 24 (±2 weeks).
Change From Baseline in Post Bronchodilator Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 52 in the Long-term Effectiveness Analysis Set	FEV1 is the maximum amount of air that can be forcefully exhaled in one second. FEVI was measured via a spirometer after the administration of the bronchodilator (Vahelva® Respimat®) at baseline and at Week 52 (±2 weeks). Post bronchodilator percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.). Change from baseline in post bronchodilator percent predicted FEV1 to Week 52 was calculated as: post bronchodilator percent predicted FEV1 value at Week 52 (±2 weeks) - post bronchodilator percent predicted FEV1 value at baseline.	At baseline and Week 52 (±2 weeks).
Transition Dyspnea Index (TDI) Focal Score at Week 24 in the Effectiveness Analysis Set	Transition dyspnea index (TDI) is a validated, interviewer-administered questionnaire that measures changes in dyspnea severity from the baseline. TDI consists of 3 individual components: functional impairment, magnitude of task, and magnitude of effort. Each component was rated by 7 grades from -3 (major deterioration) to +3 (major improvement), and were sum up to form a TDI focal score from -9 to +9, with higher scores indicating better outcomes.	At Week 24 (±2 weeks).
Transition Dyspnea Index (TDI) Focal Score at Week 52 in the Effectiveness Analysis Set	Transition dyspnea index (TDI) is a validated, interviewer-administered questionnaire that measures changes in dyspnea severity from the baseline. TDI consists of 3 individual components: functional impairment, magnitude of task, and magnitude of effort. Each component was rated by 7 grades from -3 (major deterioration) to +3 (major improvement), and were sum up to form a TDI focal score from -9 to +9, with higher scores indicating better outcomes.	At Week 52 (±2 weeks).
Transition Dyspnea Index (TDI) Focal Score at Week 24 in the Long-term Effectiveness Analysis Set	Transition dyspnea index (TDI) is a validated, interviewer-administered questionnaire that measures changes in dyspnea severity from the baseline. TDI consists of 3 individual components: functional impairment, magnitude of task, and magnitude of effort. Each component was rated by 7 grades from -3 (major deterioration) to +3 (major improvement), and were sum up to form a TDI focal score from -9 to +9, with higher scores indicating better outcomes.	At Week 24 (±2 weeks).
Transition Dyspnea Index (TDI) Focal Score at Week 52 in the Long-term Effectiveness Analysis Set	Transition dyspnea index (TDI) is a validated, interviewer-administered questionnaire that measures changes in dyspnea severity from the baseline. TDI consists of 3 individual components: functional impairment, magnitude of task, and magnitude of effort. Each component was rated by 7 grades from -3 (major deterioration) to +3 (major improvement), and were sum up to form a TDI focal score from -9 to +9, with higher scores indicating better outcomes.	At Week 52 (±2 weeks).
Number of Subjects in Each Category of Overall Evaluation in the Effectiveness Analysis Set	Overall evaluation (improved, unchanged or aggravated) was performed by investigator and was based on overall clinical assessment including change from baseline in effectiveness assessment (pre-dose percent predicted Forced Expiratory Volume in one second (FEV1), post bronchodilator percent predicted Forced Expiratory Volume in one second (FEV1), Transition dyspnea index (TDI)) after 24 weeks or 52 weeks of treatment. Improved, unchanged, aggravated are defined as below: Improved : If determined as there is any effect of maintaining or improving symptoms;; Unchanged : If symptoms have not been changed compared with before and not determined as there is any effect of maintaining symptoms;; Aggravated : If symptoms are worse than before administration. Number of subject in each category of overall evaluation (improved, unchanged or aggravated) is reported.	At baseline and at Week 24 (±2 weeks) or at Week 52 (±2 weeks).
Number of Subjects in Each Category of Overall Evaluation in the Long-term Effectiveness Analysis Set	Overall evaluation (improved, unchanged or aggravated) was performed by investigator and was based on overall clinical assessment including change from baseline in effectiveness assessment (pre-dose percent predicted Forced Expiratory Volume in one second (FEV1), post bronchodilator percent predicted Forced Expiratory Volume in one second (FEV1), Transition dyspnea index (TDI)) after 24 weeks or 52 weeks of treatment. Improved, unchanged, aggravated are defined as below: Improved : If determined as there is any effect of maintaining or improving symptoms;; Unchanged : If symptoms have not been changed compared with before and not determined as there is any effect of maintaining symptoms;; Aggravated : If symptoms are worse than before administration. Number of subject in each category of overall evaluation (improved, unchanged or aggravated) is reported.	At baseline and at Week 24 (±2 weeks) or at Week 52 (±2 weeks).
Effectiveness Rate in the Effectiveness Analysis Set	Overall evaluation (Improved, unchanged or aggravated) by investigator was based on overall clinical assessment including change from baseline in effectiveness assessment (pre-dose percent predicted Forced Expiratory Volume in one second (FEV1), post bronchodilator percent predicted Forced Expiratory Volume in one second (FEV1), Transition dyspnea index (TDI)) after 24 weeks or 52 weeks of treatment. 'Improved' was assessed as "Effective", 'Unchanged, Aggravated' were assessed as "Invalid".	At baseline and at Week 24 (±2 weeks) or at Week 52 (±2 weeks).
Effectiveness Rate in the Long-term Effectiveness Analysis Set	Overall evaluation (Improved, unchanged, aggravated or unassessable) by investigator was based on overall clinical assessment including change from baseline in effectiveness assessment (pre-dose percent predicted Forced Expiratory Volume in one second (FEV1), post bronchodilator percent predicted Forced Expiratory Volume in one second (FEV1), Transition dyspnea index (TDI)) after 24 weeks or 52 weeks of treatment. 'Improved' was assessed as "Effective", 'Unchanged, Aggravated' were assessed as "Invalid".	At baseline and at Week 24 (±2 weeks) or at Week 52 (±2 weeks).

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2016
• Primary Completion (Actual): January 20, 2021
• Study Completion (Actual): January 20, 2021

Study Registration Dates

• First Submitted: July 20, 2016
• First Submitted That Met QC Criteria: August 9, 2016
• First Posted (Estimate): August 12, 2016

Study Record Updates

• Last Update Posted (Actual): March 28, 2022
• Last Update Submitted That Met QC Criteria: February 28, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Tiotropium Bromide; Olodaterol
• Other Study ID Numbers: 1237.60

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

The data shared are the raw clinical study data sets.

• IPD Sharing Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• IPD Sharing Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No