Safety of Tiotropium + Olodaterol in Chronic Obstructive Pulmonary Disease (COPD) Patients in Taiwan: a Non-interventional Study Based on the Taiwan National Health Insurance (NHI) Data

Safety Profile of Tiotropium + Olodaterol Used as Maintenance Treatment in COPD Patients in Taiwan: a Non-interventional Study Based on the Taiwan National Health Insurance (NHI) Data

The aim of this real world study is to assess the safety profile of tiotropium/olodaterol (Tio/Olo).

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Tiotropium+Olodaterol; Device: Spiolto Respimat; Drug: Long-acting muscarinic antagonists (LAMAs); Drug: Long-acting β2-agonists (LABAs)

• Study Type: Observational
• Enrollment (Actual): 19467

Contacts and Locations

Study Locations

• China
  • Taiwan, China, 10617
    • Health Data Research Center, National Taiwan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Chinese patients with chronic obstructive pulmonary disease (COPD) in routine clinical practice in Taiwan.

Description

Patients treated with Tio+Olo:

Inclusion criteria:

1. At least one prescription for Tio+Olo (fixed dose combination (FDC) or free combination) as a new initiation between 1st January 2014 and 31st December 2019.
2. Aged ≥ 40 years on the index date.
3. At least one diagnosis of COPD at any time prior to or on the index date.
4. At least one year of continuous medical and health insurance plan prior to the index date will be required to allow for a look-back period for the covariates and identification of new use of the study drugs.
5. At least one record in the health insurance system database.

Exclusion criteria:

1. Any use of Tio+Olo in free or fixed form within one year prior to the index date.
2. Individuals with asthma, allergic rhinitis, lung cancer, interstitial lung disease, or lung transplant identified at any time prior to the index date.

Patients using other Long-acting β2-agonists/Long-acting muscarinic antagonists (LAMA/LABAs):

Inclusion criteria:

1. At least one prescription for LAMA+LABA (FDC or free combination) other than Tio/Olo as a new initiation between 1st January 2014 and 31st December 2019.
2. Aged ≥ 40 years on the index date.
3. At least one diagnosis of COPD at any time prior to or on the index date-
4. At least one year of continuous medical and health insurance plan prior to the index date will be required to allow for a look-back period for the covariates and identification of new use of the study drugs.
5. At least one record in the health insurance system database.

Exclusion criteria:

1. Any use of LAMA+LABA in free or fixed form for one year prior to the index date.
2. Individuals with asthma, allergic rhinitis, lung cancer, interstitial lung disease, or lung transplant identified at any time prior to the index date.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
COPD patients treated with tiotropium and olodaterol (Tio+Olo)	Drug: Tiotropium+Olodaterol; Tiotropium+Olodaterol; Device: Spiolto Respimat; Spiolto Respimat Inhaler device
COPD patients using other Long-acting muscarinic antagonists/Long-acting β2-agonists (LAMA/LABAs)	Drug: Long-acting muscarinic antagonists (LAMAs); Long-acting muscarinic antagonists (LAMAs); Drug: Long-acting β2-agonists (LABAs); Long-acting β2-agonists (LABAs)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence Rate of Adverse Events in Patients With COPD Treated With Tio+Olo: Potentially Recurrent Events	Incidence rate of adverse events in patients with COPD treated with Tiotropium+Olodaterol (Tio+Olo) per number of person-years is reported. From the index date until the earliest: Outcome of interest, disenrollment, the end of the study period, death, discontinuation of the index drug, addition of Inhaled corticosteroids mono on top of Tio/Olo. The incidence rate was reported as (Total number of patients in the Tio+Olo cohort experiencing an event of interest for the 1st time during the given time period) / (Total person-time at risk from current use of Tio+Olo during the given period). Urinary tract infection: (1): Diagnosis codes were primary inpatient diagnosis associated with a hospitalization. (2): Diagnosis codes were primary or secondary diagnosis associated with a hospitalization.(3): Diagnosis codes were primary or secondary diagnosis associated with a hospitalization OR associated with at least 2 outpatient/emergency visits within 30 days of each other.	From index date between 1st January 2014 until 31st December 2019. Up to 2160 days.
Incidence Rate of Adverse Events in Patients With COPD Treated With Tio+Olo: Incident Events	Incidence rate of Adverse Events (AEs) in patients with COPD treated with Tiotropium+Olodaterol (Tio+Olo) per number of person-years is reported. From index date until the earliest: Outcome of interest, disenrollment, end of the study period, death, discontinuation, use of Inhaled corticosteroids. Incident events. The incidence rate was reported as (Total number of patients in the Tio+Olo cohort experiencing an event of interest for the 1st time during the given time period) / (Total person-time at risk from current use of Tio+Olo during the given period). Urinary tract infection: (1): Diagnosis codes were primary inpatient diagnosis associated with a hospitalization. (2): Diagnosis codes were primary or secondary diagnosis associated with a hospitalization.(3): Diagnosis codes were primary or secondary diagnosis associated with a hospitalization OR associated with at least 2 outpatient/emergency visits within 30 days of each other.	From index date between 1st January 2014 until 31st December 2019. Up to 2160 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline Characteristics of Patients Who Initiated Tio+Olo or Other LAMA/LABA: Sex	Number of patients by sex according to whether they started Tio+Olo or another LAMA/LABA	At index date between 2014-2019. Up to 2160 days.
Baseline Characteristics of Patients Who Initiated Tio+Olo or Other LAMA/LABA: Age	Number of patients by age groups according to whether they started Tio+Olo or another LAMA/LABA. The reported age groups are: 40-59, 60-79 and 80+.	At index date between 2014-2019
Baseline Characteristics of Patients Who Initiated Tio+Olo or Other LAMA/LABA: Calendar Year of Cohort Entry	Number of patients by Calendar year of cohort entry according to whether they started Tio+Olo or another LAMA/LABA. The reported year groups are: 2014, 2015, 2016, 2017, 2018 and 2019.	At index date between 2014-2019
Baseline Characteristics of Patients Who Initiated Tio+Olo or Other LAMA/LABA: Season of Cohort Entry Date	Number of patients by season of cohort entry date according to whether they started Tio+Olo or another LAMA/LABA. The reported seasons are: Spring (Mar-May), Summer (Jun-Aug), Fall (Sep-Nov) and Winter (Dec-Feb).	At index date between 2014-2019
Baseline Period: Characteristics 1 Year Pre-index Comparison Between Patients Who Initiated Tio+Olo or Other LAMA/LABA: Specific Previous COPD Treatment	Number of patients by specific previous COPD treatment during the 1 year pre-index baseline period according to whether they started Tio+Olo or another LAMA/LABA is reported. The treatments were: Long-acting muscarinic antagonists (LAMA) monotherapy, Long-acting β2-agonists (LABA) monotherapy, Inhaled corticosteroids (ICS) monotherapy, ICS containing therapy and LAMA+LABA free combinations.	Baseline period: 360 consecutive days ending the day before the index date. Up to 360 days.
Baseline Period: Characteristics 1 Year Pre-index Comparison Between Patients Who Initiated Tio+Olo or Other LAMA/LABA: Use of Other Respiratory Drugs	Number of patients by use of other respiratory drugs during the 1 year pre-index baseline period according to whether they started Tio+Olo or another LAMA/LABA is reported. The treatments were: Mucolytics, Theophylline, Short-acting beta-agonists and Short-acting muscarinic antagonists.	Baseline period: 360 consecutive days ending the day before the index date. Up to 360 days.
Baseline Period: Characteristics 1 Year Pre-index Comparison Between Patients Who Initiated Tio+Olo or Other LAMA/LABA: Moderate COPD Exacerbation in 1 Year Prior to Index Date	Number of patients by moderate Chronic Obstructive Pulmonary Disease (COPD) exacerbation in 1 year prior to index date according to whether they started Tio+Olo or another LAMA/LABA is reported. Categorized as 0, 1, or 2+ according to the frequency of previous acute COPD exacerbation in 1 year for each patient.	Baseline period: 360 consecutive days ending the day before the index date. Up to 360 days.
Baseline Period: Characteristics 1 Year Pre-index Comparison Between Patients Who Initiated Tio+Olo or Other LAMA/LABA: Severe COPD Exacerbation in 1 Year Prior to Index Date	Number of patients by severe Chronic Obstructive Pulmonary Disease (COPD) exacerbation in 1 year prior to index date according to whether they started Tio+Olo or another LAMA/LABA is reported. Categorized as 0, 1, or 2+.	Baseline period: 360 consecutive days ending the day before the index date. Up to 360 days.
Baseline Period: Characteristics 1 Year Pre-index Comparison Between Patients Who Initiated Tio+Olo or Other LAMA/LABA: All COPD Exacerbation in 1 Year Prior to Index Date	Number of patients by Chronic Obstructive Pulmonary Disease (COPD) exacerbations in 1 year prior to index date according to whether they started Tio+Olo or another LAMA/LABA is reported. Categorized as 0, 1, or 2+.	Baseline period: 360 consecutive days ending the day before the index date. Up to 360 days.
Baseline Period: Characteristics Pre-index Comparison Between Patients Who Initiated Tio+Olo or Other LAMA/LABA: Moderate COPD Exacerbation 30 Days Prior to Index Date	Number of patients by moderate Chronic Obstructive Pulmonary Disease (COPD) exacerbation in 30 days prior to index date according to whether they started Tio+Olo or another LAMA/LABA is reported. Categorized as 0, 1, or 2+.	Baseline period: 30 consecutive days ending the day before the index date. Up to 30 days.
Baseline Period: Characteristics Pre-index Comparison Between Patients Who Initiated Tio+Olo or Other LAMA/LABA: Severe COPD Exacerbation 30 Days Prior to Index Date	Number of patients by severe Chronic Obstructive Pulmonary Disease (COPD) exacerbation in 30 days prior to index date according to whether they started Tio+Olo or another LAMA/LABA is reported. Categorized as 0, 1, or 2+.	Baseline period: 30 consecutive days ending the day before the index date. Up to 30 days.
Baseline Period: Characteristics Pre-index Comparison Between Patients Who Initiated Tio+Olo or Other LAMA/LABA: All COPD Exacerbation 30 Days Prior to Index Date	Number of patients by Chronic Obstructive Pulmonary Disease (COPD) exacerbations in 30 days prior to index date according to whether they started Tio+Olo or another LAMA/LABA is reported. Categorized as 0, 1, or 2+.	Baseline period: 30 consecutive days ending the day before the index date. Up to 30 days.
Baseline Period: Characteristics 1 Year Pre-index Comparison Between Patients Who Initiated Tio+Olo or Other LAMA/LABA: Hospitalizations Caused by Exacerbation of COPD in 1 Year Prior to Index Date	Number of hospitalizations caused by Chronic Obstructive Pulmonary Disease (COPD) exacerbations in 1 year prior to index date according to whether they started Tio+Olo or another LAMA/LABA is reported. Categorized as 0, 1, or 2+.	Baseline period: 360 consecutive days ending the day before the index date. Up to 360 days.
Baseline Period: Characteristics 1 Year Pre-index Comparison Between Patients Who Initiated Tio+Olo or Other LAMA/LABA: All-cause Hospitalizations in 1 Year Prior to Index Date	Number of all-cause hospitalizations in 1 year prior to index date according to whether they started Tio+Olo or another LAMA/LABA is reported. Categorized as 0, 1, or 2+.	Baseline period: 360 consecutive days ending the day before the index date. Up to 360 days.
Baseline Period: Characteristics 1 Year Pre-index Comparison Between Patients Who Initiated Tio+Olo or Other LAMA/LABA: Comorbidities in 1 Year Prior to Index Date	Number of participants with comorbidities in 1 year prior to index date according to whether they started Tio+Olo or another LAMA/LABA is reported. The following comorbidities are reported: Cardiovascular disease, Cerebrovascular disease, Diabetes, Chronic kidney disease, Pneumonia, Cancer and Cirrhosis.	Baseline period: 360 consecutive days ending the day before the index date. Up to 360 days.
Baseline Period: Characteristics 1 Year Pre-index Comparison Between Patients Who Initiated Tio+Olo or Other LAMA/LABA: Charlson Comorbidity Index (CCI) in 1 Year Prior to Index Date	Charlson Comorbidity Index (CCI) according to whether they started Tio+Olo or another LAMA/LABA is reported. The CCI (using Deyo version) is a comorbidity index used to evaluate survival rate in patients with multiple comorbidities. 17 comorbidities were assessed with different weights, and the total score was determined by adding the scores of each comorbidity. The total score goes from 0 to 37, with higher values predicting a higher mortality rate.	Baseline period: 360 consecutive days ending the day before the index date. Up to 360 days.
Baseline Period: Characteristics 1 Year Pre-index Comparison Between Patients Who Initiated Tio+Olo or Other LAMA/LABA: History of Medications Dispensed in 1 Year Prior to Index Date	Number of participants with history of medications dispensed in 1 year prior to index date according to whether they started Tio+Olo or another LAMA/LABA is reported. The following medications are reported: Antihypertensives, Antiarrhythmics, Nitrates, Heart failure medications, Lipid-lowering medications, Blood glucose-lowering medications, Anticoagulants and antiplatelet agents, Antibiotics and Antineoplastic agents.	Baseline period: 360 consecutive days ending the day before the index date. Up to 360 days.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2022
• Primary Completion (Actual): December 7, 2022
• Study Completion (Actual): December 7, 2022

Study Registration Dates

• First Submitted: May 23, 2022
• First Submitted That Met QC Criteria: May 23, 2022
• First Posted (Actual): May 26, 2022

Study Record Updates

• Last Update Posted (Estimated): December 4, 2024
• Last Update Submitted That Met QC Criteria: October 15, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Respiratory System Agents; Anti-Asthmatic Agents; Bronchodilator Agents; Cholinergic Antagonists; Parasympatholytics; Tiotropium Bromide; Olodaterol; Cholinergic Agents; Muscarinic Antagonists
• Other Study ID Numbers: 1237-0109

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).

For more details refer to: https://www.mystudywindow.com/msw/datatransparency

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No