Comparative Effectiveness and Safety of Tiotropium and Olodaterol in Comparison to LABA/ICS

Effectiveness and Safety of Maintenance Treatment With Combination of Tiotropium and Olodaterol in Comparison to Maintenance Treatment With a Combination of Inhaled Corticosteroids and Long-acting β2 Agonists in COPD Patients

The primary objective is to compare the effectiveness of maintenance therapy initiation with the combination treatment Tiotropium and Olodaterol (Olo+Tio) compared with LABA/ICS combination in COPD as the time to the first COPD exacerbation.

Secondary objectives are to compare patients treated with Tio+Olo and patients treated with LABA/ ICS combination.

Study Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: Drug: Tiotropium bromide + Olodaterol; Drug: LABA/ICS

• Study Type: Observational
• Enrollment (Actual): 42953

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Watertown, Massachusetts, United States, 02472
      • HealthCore, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects with COPD inititated with Tio+Olo in comparison to patients treated with ICS/LABA/LAMA

Description

Inclusion Criteria:

1. At least one prescription for Tio+Olo combined inhaler or a LABA/ICS combined inhaler between 1 January 2013 and 31 March 2019.

   1. The first dispensing of either Tio+Olo or LABA/ICS combined inhaler will be defined as the index date.
   2. For the main analyses, only fixed dose combination (FDC) inhalers will be included. Sensitivity analyses will also accept free combinations of LABA/ICS.
2. At least one diagnosis of COPD at any time prior to the index date.
3. At least one year of continuous medical and pharmacy health plan eligibility prior to the index date will be required to allow a baseline period for the covariates and identification of new use of the study drugs.

Exclusion Criteria:

1. To increase the likelihood of a true diagnosis of COPD, we will exclude:

   1. All patients less than 40 years of age on the index date, and
   2. All patients with a diagnosis of asthma in the year prior to the index date
2. To limit the population to those without severe lung compromise outside of COPD, we will exclude individuals with lung cancer, interstitial lung disease, or lung transplant identified at any time prior to the index date
3. To restrict the cohort to new users of Tio+Olo or LABA/ICS, we will exclude any individual with use of either Tio+Olo, LABA/ICS, or LABA/LAMA/ICS combination therapy in free or fixed form for at least one year 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
Patients initiating Tiotropium+Olodaterol therapy	Drug: Tiotropium bromide + Olodaterol; Tiotropium bromide + Olodaterol
Patients initiating Long-acting beta agonist/inhaled corticosteroid therapy	Drug: LABA/ICS; Long-acting beta2-agonist and Inhaled corticosteroids (LABA and ICS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	Incidence rate of Chronic Obstructive Pulmonary Disease (COPD) exacerbation after cohort entry. The event was defined as follows: Severe exacerbation: Hospitalization with a principal discharge diagnosis of COPD. or Moderate exacerbation: An emergency department (ED) visit with a discharge diagnosis of COPD, or, an antibiotic for a respiratory condition dispensed the same day as an oral corticosteroid.	From cohort entry (index date) until the occurrence of a hospitalization for COPD (severe exacerbation), ED visit for COPD or prescription of an antibiotic and oral corticosteroid on the same day (moderate exacerbation). Up to one year after cohort entry.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence Rate of First Hospitalization for Community-acquired Pneumonia	Incidence rate of first hospitalization for community-acquired pneumonia (serious pneumonia). Pneumonia was defined using ICD-9-CM diagnoses and ICD-10 diagnosis codes.	From cohort entry (index date) until the occurrence of first hospitalization for community-acquired pneumonia (serious pneumonia). Up to one year after cohort entry.
Incidence Rate of the First Date of a Pharmacy Dispensing Indicating Escalation (Original Case Definition) to Triple Therapy	Incidence rate of the first date of a pharmacy dispensing indicating escalation to triple therapy, (i.e., addition of Inhaled Corticosteroids to Tiotropium and Olodaterol or a Long-acting Muscarinic Antagonists to long-acting beta agonist / inhaled corticosteroid therapy).	From cohort entry (index date) until the escalation, up to one year after cohort entry.
Incidence Rate of the First Date of a Pharmacy Dispensing Indicating Escalation (Alternative Case Definition) to Triple Therapy	Incidence rate of the first date of a pharmacy dispensing indicating escalation to triple therapy. Based on feedback from clinical experts during review of study results, an alternative post-hoc definition was also assessed in which initiation of any treatment including simultaneous LABA (long-acting beta agonist) /LAMA (Long-acting Muscarinic Antagonists) /ICS (inhaled corticosteroid therapy) use in free or fixed combination was counted as an outcome.	From cohort entry (index date) until the escalation, up to one year after cohort entry.
Incidence Rate of Any Element of a Composite Outcome Including Exacerbation, Hospitalization for Pneumonia, or Escalation (Original Case Definition) to Triple Therapy	Incidence rate of any element of a composite outcome including exacerbation, hospitalization for pneumonia, or escalation (original case definition) to triple therapy. Exacerbation was defined as follows: Severe exacerbation: Hospitalization with a principal discharge diagnosis of COPD. Moderate exacerbation: An emergency department (ED) visit with a discharge diagnosis of COPD, or, an antibiotic for a respiratory condition dispensed the same day as an oral corticosteroid. Pneumonia was defined using ICD-9-CM diagnoses and ICD-10 diagnosis codes. Escalation was defined as the addition of Inhaled Corticosteroids to Tiotropium and Olodaterol or a Long-acting Muscarinic Antagonists to long-acting beta agonist / inhaled corticosteroid therapy.	From cohort entry (index date) until exacerbation, hospitalization (for community-acquired pneumonia) or escalation, up to one year after cohort entry.
Incidence Rate of Any Element of a Composite Outcome Including Exacerbation, Hospitalization for Pneumonia, or Escalation (Alternative Case Definition) to Triple Therapy	Incidence rate of any element of a composite outcome including exacerbation, hospitalization for pneumonia, or escalation (alternative case definition) to triple therapy. Exacerbation was defined as follows: Severe exacerbation: Hospitalization with a principal discharge diagnosis of COPD. Moderate exacerbation: An emergency department (ED) visit with a discharge diagnosis of COPD, or, an antibiotic for a respiratory condition dispensed the same day as an oral corticosteroid. Pneumonia was defined using ICD-9-CM diagnoses and ICD-10 diagnosis codes. Escalation was defined as the initiation of any treatment including simultaneous LABA (long-acting beta agonist) /LAMA (Long-acting Muscarinic Antagonists) /ICS (inhaled corticosteroid therapy) use in free or fixed combination.	From cohort entry (index date) until exacerbation, hospitalization (for community-acquired pneumonia) or escalation, up to one year after cohort entry.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Quint JK, Montonen J, Esposito DB, He X, Koerner L, Wallace L, de la Hoz A, Miravitlles M. Effectiveness and Safety of COPD Maintenance Therapy with Tiotropium/Olodaterol versus LABA/ICS in a US Claims Database. Adv Ther. 2021 May;38(5):2249-2270. doi: 10.1007/s12325-021-01646-5. Epub 2021 Mar 15.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2019
• Primary Completion (Actual): November 4, 2019
• Study Completion (Actual): November 4, 2019

Study Registration Dates

• First Submitted: October 23, 2019
• First Submitted That Met QC Criteria: October 23, 2019
• First Posted (Actual): October 24, 2019

Study Record Updates

• Last Update Posted (Actual): November 15, 2021
• Last Update Submitted That Met QC Criteria: November 12, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Tiotropium Bromide; Bromides; Olodaterol
• Other Study ID Numbers: 1237-0093

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, except for the following exclusions:

1. studies in products where Boehringer Ingelheim is not the license holder;
2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials;
3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization).

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

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