NCT04138758

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

Completed Results posted Last updated 15 November 2021

What this trial tests

trial testing Tiotropium bromide + Olodaterol in COPD in 42,953 participants. Completed in 4 November 2019.

Timeline

1 November 2019

Primary endpoint
4 November 2019

4 November 2019

Quick facts

Lead sponsor	Boehringer Ingelheim
Status	Completed
Study type	OBSERVATIONAL
Enrollment	42,953
Start date	1 November 2019
Primary completion	4 November 2019
Estimated completion	4 November 2019
Sites	1 location across United States

Drugs / interventions tested

• Tiotropium bromide + Olodaterol
• LABA/ICS

Conditions studied

• COPD — all drugs for COPD →

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

40 and older, any sex, with COPD. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Primary · 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.

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.

Group	Value	95% CI
Tiotropium + Olodaterol	1.63	1.47 – 1.81
Long-acting Beta Agonist / Inhaled Corticosteroid Therapy	2.43	2.37 – 2.49

Incidence Rate of First Hospitalization for Community-acquired Pneumonia Secondary · 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 first hospitalization for community-acquired pneumonia (serious pneumonia). Pneumonia was defined using ICD-9-CM diagnoses and ICD-10 diagnosis codes.

Group	Value	95% CI
Tiotropium + Olodaterol	0.23	0.18 – 0.30
Long-acting Beta Agonist / Inhaled Corticosteroid Therapy	0.34	0.32 – 0.37

Incidence Rate of the First Date of a Pharmacy Dispensing Indicating Escalation (Original Case Definition) to Triple Therapy Secondary · 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 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).

Group	Value	95% CI
Tiotropium + Olodaterol	0.54	0.46 – 0.64
Long-acting Beta Agonist / Inhaled Corticosteroid Therapy	2.90	2.84 – 2.97

Incidence Rate of the First Date of a Pharmacy Dispensing Indicating Escalation (Alternative Case Definition) to Triple Therapy Secondary · 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 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.

Group	Value	95% CI
Tiotropium + Olodaterol	0.57	0.48 – 0.67
Long-acting Beta Agonist / Inhaled Corticosteroid Therapy	3.14	3.08 – 3.21

Incidence Rate of Any Element of a Composite Outcome Including Exacerbation, Hospitalization for Pneumonia, or Escalation (Original Case Definition) to Triple Therapy Secondary · 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 (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 Inh

Group	Value	95% CI
Tiotropium + Olodaterol	2.14	1.96 – 2.34
Long-acting Beta Agonist / Inhaled Corticosteroid Therapy	5.45	5.36 – 5.54

Incidence Rate of Any Element of a Composite Outcome Including Exacerbation, Hospitalization for Pneumonia, or Escalation (Alternative Case Definition) to Triple Therapy Secondary · 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. 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 o

Group	Value	95% CI
Tiotropium + Olodaterol	2.16	1.98 – 2.37
Long-acting Beta Agonist / Inhaled Corticosteroid Therapy	5.67	5.58 – 5.77

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Long-acting muscarinic antagonist (LAMA) plus long-acting beta-agonist (LABA) versus LABA plus inhaled corticosteroid (ICS) for stable chronic obstructive pulmonary disease.
   Fukuda N, Horita N, Kaneko A, Goto A, et al · · 2023 · cited 10× · PMID 37276335 · DOI 10.1002/14651858.cd012066.pub3
2. Effectiveness and Safety of COPD Maintenance Therapy with Tiotropium/Olodaterol versus LABA/ICS in a US Claims Database.
   Quint JK, Montonen J, Esposito DB, He X, et al · · 2021 · cited 6× · PMID 33721209 · DOI 10.1007/s12325-021-01646-5