Trial Outcomes & Findings for Impact of Tiotropium Add-on Therapy in Patients With Asthma (NCT NCT03964220)

Results Overview

Exacerbations will be defined as either a hospitalization with a primary diagnosis of asthma, an emergency room (ER) visit with a primary diagnosis of asthma, an asthma exacerbation diagnosis recorded.

Recruitment status

COMPLETED

Target enrollment

7857 participants

Primary outcome timeframe

From baseline until end of follow-up, up to 3 years

Results posted on

2020-11-03

Participant Flow

A retrospective cohort data analysis evaluated the effectiveness of add on therapy with Tiotropium Respimat® 1.25 microgram comparing to increasing the dose of Inhaled Corticosteroid (ICS) in patients with a diagnosis of Asthma and on ICS/Long-acting beta-agonist (LABA) therapy.

This study included asthma patients from two retrospective data sources (IMS Pharmetrics and EMRClaims+) after propensity score matching based on ICS/LABA dose on initiation date, demographics, Charlson Comorbidity index (CCI) score, specific comorbidities, medications and asthma control status.

Participant milestones

Participant milestones
Measure	Tiotropium Respimat® (Tio Group) 1.25 microgram (mcg) of solution of inhalation of Tiotropium Respimat® added-on to Inhaled Corticosteroid (ICS)/long-acting beta-agonists (LABA) therapy. Advair Diskus, Advair HFA, AirDuo, Breo, Dulera or Symbicort were used for the ICS/LABA therapy from low dose (Advair Diskus (100mcg), Advair HFA (45mcg), AirDuo (55mcg), Breo (100mcg), Dulera (100mcg), Symbicort (80mcg)), to medium dose (Advair Diskus (250mcg), Advair HFA (115mcg), AirDuo (113mcg)) and high dose (Advair Diskus (500mcg), Advair HFA (230mcg), AirDuo (232mcg), Breo (200mcg), Dulera (200mcg), Symbicort (160mcg)).	Inhaled Corticosteroid/Long-acting Beta-agonist (NonTio Group) Low dose ICS/LABA to medium/high dose ICS/LABA or from baseline medium dose ICS/LABA to high dose ICS/LABA or an additional prescription/refill of high-dose ICS/LABA following the first prescription of baseline high dose ICS/LABA within the study period. Advair Diskus, Advair HFA, AirDuo, Breo, Dulera or Symbicort were used for the ICS/LABA therapy from low dose (Advair Diskus (100mcg), Advair HFA (45mcg), AirDuo (55mcg), Breo (100mcg), Dulera (100mcg), Symbicort (80mcg)), to medium dose (Advair Diskus (250mcg), Advair HFA (115mcg), AirDuo (113mcg)) and high dose (Advair Diskus (500mcg), Advair HFA (230mcg), AirDuo (232mcg), Breo (200mcg), Dulera (200mcg), Symbicort (160mcg)).
Overall Study STARTED	2619	5238
Overall Study COMPLETED	2619	5238
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tiotropium Respimat® (Tio Group) n=2619 Participants 1.25 microgram (mcg) of solution of inhalation of Tiotropium Respimat® added-on to Inhaled Corticosteroid (ICS)/long-acting beta-agonists (LABA) therapy. Advair Diskus, Advair HFA, AirDuo, Breo, Dulera or Symbicort were used for the ICS/LABA therapy from low dose (Advair Diskus (100mcg), Advair HFA (45mcg), AirDuo (55mcg), Breo (100mcg), Dulera (100mcg), Symbicort (80mcg)), to medium dose (Advair Diskus (250mcg), Advair HFA (115mcg), AirDuo (113mcg)) and high dose (Advair Diskus (500mcg), Advair HFA (230mcg), AirDuo (232mcg), Breo (200mcg), Dulera (200mcg), Symbicort (160mcg)).	Inhaled Corticosteroid/Long-acting Beta-agonist (NonTio Group) n=5238 Participants Low dose ICS/LABA to medium/high dose ICS/LABA or from baseline medium dose ICS/LABA to high dose ICS/LABA or an additional prescription/refill of high-dose ICS/LABA following the first prescription of baseline high dose ICS/LABA within the study period. Advair Diskus, Advair HFA, AirDuo, Breo, Dulera or Symbicort were used for the ICS/LABA therapy from low dose (Advair Diskus (100mcg), Advair HFA (45mcg), AirDuo (55mcg), Breo (100mcg), Dulera (100mcg), Symbicort (80mcg)), to medium dose (Advair Diskus (250mcg), Advair HFA (115mcg), AirDuo (113mcg)) and high dose (Advair Diskus (500mcg), Advair HFA (230mcg), AirDuo (232mcg), Breo (200mcg), Dulera (200mcg), Symbicort (160mcg)).	Total n=7857 Participants Total of all reporting groups
Age, Continuous	45.12 Years STANDARD_DEVIATION 15.38 • n=2619 Participants	44.77 Years STANDARD_DEVIATION 15.43 • n=5238 Participants	44.89 Years STANDARD_DEVIATION 15.41 • n=7857 Participants
Sex: Female, Male Female	1802 Participants n=2619 Participants	3576 Participants n=5238 Participants	5378 Participants n=7857 Participants
Sex: Female, Male Male	817 Participants n=2619 Participants	1662 Participants n=5238 Participants	2479 Participants n=7857 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: From baseline until end of follow-up, up to 3 years

Population: This study included asthma patients from two retrospective data sources (IMS Pharmetrics and EMRClaims+) after propensity score matching based on ICS/LABA dose on initiation date, demographics, Charlson Comorbidity index (CCI) score, specific comorbidities, medications and asthma control status.

Exacerbations will be defined as either a hospitalization with a primary diagnosis of asthma, an emergency room (ER) visit with a primary diagnosis of asthma, an asthma exacerbation diagnosis recorded.

Outcome measures

Outcome measures
Measure	Tiotropium Respimat® (Tio Group) n=2619 Participants 1.25 microgram (mcg) of solution of inhalation of Tiotropium Respimat® added-on to Inhaled Corticosteroid (ICS)/long-acting beta-agonists (LABA) therapy. Advair Diskus, Advair HFA, AirDuo, Breo, Dulera or Symbicort were used for the ICS/LABA therapy from low dose (Advair Diskus (100mcg), Advair HFA (45mcg), AirDuo (55mcg), Breo (100mcg), Dulera (100mcg), Symbicort (80mcg)), to medium dose (Advair Diskus (250mcg), Advair HFA (115mcg), AirDuo (113mcg)) and high dose (Advair Diskus (500mcg), Advair HFA (230mcg), AirDuo (232mcg), Breo (200mcg), Dulera (200mcg), Symbicort (160mcg)).	Inhaled Corticosteroid/Long-acting Beta-agonist (NonTio Group) n=5238 Participants Low dose ICS/LABA to medium/high dose ICS/LABA or from baseline medium dose ICS/LABA to high dose ICS/LABA or an additional prescription/refill of high-dose ICS/LABA following the first prescription of baseline high dose ICS/LABA within the study period. Advair Diskus, Advair HFA, AirDuo, Breo, Dulera or Symbicort were used for the ICS/LABA therapy from low dose (Advair Diskus (100mcg), Advair HFA (45mcg), AirDuo (55mcg), Breo (100mcg), Dulera (100mcg), Symbicort (80mcg)), to medium dose (Advair Diskus (250mcg), Advair HFA (115mcg), AirDuo (113mcg)) and high dose (Advair Diskus (500mcg), Advair HFA (230mcg), AirDuo (232mcg), Breo (200mcg), Dulera (200mcg), Symbicort (160mcg)).
Time to First Exacerbation	340.656 Days Standard Deviation 428.061	123.151 Days Standard Deviation 152.600

SECONDARY outcome

Timeframe: At 6 month and 1 year of follow-up

Population: This study included asthma patients from two retrospective data sources (IMS Pharmetrics and EMRClaims+) after propensity score matching based on ICS/LABA dose on initiation date, demographics, Charlson Comorbidity index (CCI) score, specific comorbidities, medications and asthma control status.

Exacerbation rate per 100 person-years. Follow-up period was from index date (date of the first prescription for Tiotropium Respimat® 1.25 mcg in Tio group; date of the first prescription from low to medium/high does or medium to high does or additional high-does of Inhaled Corticosteroid (ICS)/long-acting beta-agonists (LABA) for NonTio group).

Outcome measures

Outcome measures
Measure	Tiotropium Respimat® (Tio Group) n=2619 Participants 1.25 microgram (mcg) of solution of inhalation of Tiotropium Respimat® added-on to Inhaled Corticosteroid (ICS)/long-acting beta-agonists (LABA) therapy. Advair Diskus, Advair HFA, AirDuo, Breo, Dulera or Symbicort were used for the ICS/LABA therapy from low dose (Advair Diskus (100mcg), Advair HFA (45mcg), AirDuo (55mcg), Breo (100mcg), Dulera (100mcg), Symbicort (80mcg)), to medium dose (Advair Diskus (250mcg), Advair HFA (115mcg), AirDuo (113mcg)) and high dose (Advair Diskus (500mcg), Advair HFA (230mcg), AirDuo (232mcg), Breo (200mcg), Dulera (200mcg), Symbicort (160mcg)).	Inhaled Corticosteroid/Long-acting Beta-agonist (NonTio Group) n=5238 Participants Low dose ICS/LABA to medium/high dose ICS/LABA or from baseline medium dose ICS/LABA to high dose ICS/LABA or an additional prescription/refill of high-dose ICS/LABA following the first prescription of baseline high dose ICS/LABA within the study period. Advair Diskus, Advair HFA, AirDuo, Breo, Dulera or Symbicort were used for the ICS/LABA therapy from low dose (Advair Diskus (100mcg), Advair HFA (45mcg), AirDuo (55mcg), Breo (100mcg), Dulera (100mcg), Symbicort (80mcg)), to medium dose (Advair Diskus (250mcg), Advair HFA (115mcg), AirDuo (113mcg)) and high dose (Advair Diskus (500mcg), Advair HFA (230mcg), AirDuo (232mcg), Breo (200mcg), Dulera (200mcg), Symbicort (160mcg)).
Rate of Exacerbation at 6 Months and 1 Year of Follow-up At 6 months of follow-up	41.40 Events per 100 person-years	116.07 Events per 100 person-years
Rate of Exacerbation at 6 Months and 1 Year of Follow-up At 1 year of follow-up	15.65 Events per 100 person-years	57.24 Events per 100 person-years

SECONDARY outcome

Timeframe: During follow-up period, From baseline until end of follow-up, up to 3 years

Population: This study included asthma patients from two retrospective data sources (IMS Pharmetrics and EMRClaims+) after propensity score matching based on ICS/LABA dose on initiation date, demographics, Charlson Comorbidity index (CCI) score, specific comorbidities, medications and asthma control status.

Follow-up period was from index date (date of the first prescription for Tiotropium Respimat® 1.25 mcg in Tio group; date of the first prescription from low to medium/high does or medium to high does or additional high-does of Inhaled Corticosteroid (ICS)/long-acting beta-agonists (LABA) for NonTio group) and up to 3 years of study period.

Outcome measures

Outcome measures
Measure	Tiotropium Respimat® (Tio Group) n=2619 Participants 1.25 microgram (mcg) of solution of inhalation of Tiotropium Respimat® added-on to Inhaled Corticosteroid (ICS)/long-acting beta-agonists (LABA) therapy. Advair Diskus, Advair HFA, AirDuo, Breo, Dulera or Symbicort were used for the ICS/LABA therapy from low dose (Advair Diskus (100mcg), Advair HFA (45mcg), AirDuo (55mcg), Breo (100mcg), Dulera (100mcg), Symbicort (80mcg)), to medium dose (Advair Diskus (250mcg), Advair HFA (115mcg), AirDuo (113mcg)) and high dose (Advair Diskus (500mcg), Advair HFA (230mcg), AirDuo (232mcg), Breo (200mcg), Dulera (200mcg), Symbicort (160mcg)).	Inhaled Corticosteroid/Long-acting Beta-agonist (NonTio Group) n=5238 Participants Low dose ICS/LABA to medium/high dose ICS/LABA or from baseline medium dose ICS/LABA to high dose ICS/LABA or an additional prescription/refill of high-dose ICS/LABA following the first prescription of baseline high dose ICS/LABA within the study period. Advair Diskus, Advair HFA, AirDuo, Breo, Dulera or Symbicort were used for the ICS/LABA therapy from low dose (Advair Diskus (100mcg), Advair HFA (45mcg), AirDuo (55mcg), Breo (100mcg), Dulera (100mcg), Symbicort (80mcg)), to medium dose (Advair Diskus (250mcg), Advair HFA (115mcg), AirDuo (113mcg)) and high dose (Advair Diskus (500mcg), Advair HFA (230mcg), AirDuo (232mcg), Breo (200mcg), Dulera (200mcg), Symbicort (160mcg)).
Health Care Resource Utilization (HCRU) During Follow-up Hospitalization (all cause)	23.97 Events per 100 person-years	46.51 Events per 100 person-years
Health Care Resource Utilization (HCRU) During Follow-up Hospitalization (asthma related)	4.89 Events per 100 person-years	20.27 Events per 100 person-years
Health Care Resource Utilization (HCRU) During Follow-up Emergency room (ER) visit (all cause)	45.00 Events per 100 person-years	84.67 Events per 100 person-years
Health Care Resource Utilization (HCRU) During Follow-up ER visit (asthma related)	12.23 Events per 100 person-years	47.70 Events per 100 person-years
Health Care Resource Utilization (HCRU) During Follow-up Outpatient (OP) visit (all cause)	206.92 Events per 100 person-years	232.55 Events per 100 person-years
Health Care Resource Utilization (HCRU) During Follow-up OP visit (asthma related)	133.06 Events per 100 person-years	158.61 Events per 100 person-years

SECONDARY outcome

Timeframe: From baseline until end of follow-up, up to 3 years

Population: This study included asthma patients from two retrospective data sources (IMS Pharmetrics and EMRClaims+) after propensity score matching based on ICS/LABA dose on initiation date, demographics, CCI score, specific comorbidities, medications and asthma control status. Analysis conducted with participants with non-missing endpoint results.

Follow-up period was from index date (date of the first prescription for Tiotropium Respimat® 1.25 mcg in Tio group; date of the first prescription from low to medium/high does or medium to high does or additional high-does of Inhaled Corticosteroid (ICS)/long-acting beta-agonists (LABA) for NonTio group) and up to 3 years of study period. FEV1 score range from 0 to 100. Higher FEV1 score suggests normal lung function, while lower for dangerous. Only the descriptive statistics of FEV1 score were reported other than change of FEV1 score from baseline due to lack of enough data points.

Outcome measures

Outcome measures
Measure	Tiotropium Respimat® (Tio Group) n=13 Participants 1.25 microgram (mcg) of solution of inhalation of Tiotropium Respimat® added-on to Inhaled Corticosteroid (ICS)/long-acting beta-agonists (LABA) therapy. Advair Diskus, Advair HFA, AirDuo, Breo, Dulera or Symbicort were used for the ICS/LABA therapy from low dose (Advair Diskus (100mcg), Advair HFA (45mcg), AirDuo (55mcg), Breo (100mcg), Dulera (100mcg), Symbicort (80mcg)), to medium dose (Advair Diskus (250mcg), Advair HFA (115mcg), AirDuo (113mcg)) and high dose (Advair Diskus (500mcg), Advair HFA (230mcg), AirDuo (232mcg), Breo (200mcg), Dulera (200mcg), Symbicort (160mcg)).	Inhaled Corticosteroid/Long-acting Beta-agonist (NonTio Group) n=26 Participants Low dose ICS/LABA to medium/high dose ICS/LABA or from baseline medium dose ICS/LABA to high dose ICS/LABA or an additional prescription/refill of high-dose ICS/LABA following the first prescription of baseline high dose ICS/LABA within the study period. Advair Diskus, Advair HFA, AirDuo, Breo, Dulera or Symbicort were used for the ICS/LABA therapy from low dose (Advair Diskus (100mcg), Advair HFA (45mcg), AirDuo (55mcg), Breo (100mcg), Dulera (100mcg), Symbicort (80mcg)), to medium dose (Advair Diskus (250mcg), Advair HFA (115mcg), AirDuo (113mcg)) and high dose (Advair Diskus (500mcg), Advair HFA (230mcg), AirDuo (232mcg), Breo (200mcg), Dulera (200mcg), Symbicort (160mcg)).
Change in Lung Function (Forced Expiratory Volume in 1 Second (FEV1) Score) at Baseline and Follow up Period	77.77 Score on a scale Standard Deviation 20.16	85.69 Score on a scale Standard Deviation 20.77

SECONDARY outcome

Timeframe: From baseline until end of follow-up, up to 3 years

Population: This study included asthma patients from two retrospective data sources (IMS Pharmetrics and EMRClaims+) after propensity score matching based on ICS/LABA dose on initiation date, demographics, CCI score, specific comorbidities, medications and asthma control status. Analysis conducted with participants with non-missing endpoint results.

Follow-up period was from index date (date of the first prescription for Tiotropium Respimat® 1.25 mcg in Tio group; date of the first prescription from low to medium/high does or medium to high does or additional high-does of Inhaled Corticosteroid (ICS)/long-acting beta-agonists (LABA) for NonTio group) and up to 3 years of study period. ACT score is based on a range of 5 to 25. Higher score indicates better asthma control. A score of 19 or less may be a sign that asthma symptoms not under control. Only the descriptive statistics of ACT score were reported other than change of ACT score from baseline due to lack of enough data points.

Outcome measures

Outcome measures
Measure	Tiotropium Respimat® (Tio Group) n=23 Participants 1.25 microgram (mcg) of solution of inhalation of Tiotropium Respimat® added-on to Inhaled Corticosteroid (ICS)/long-acting beta-agonists (LABA) therapy. Advair Diskus, Advair HFA, AirDuo, Breo, Dulera or Symbicort were used for the ICS/LABA therapy from low dose (Advair Diskus (100mcg), Advair HFA (45mcg), AirDuo (55mcg), Breo (100mcg), Dulera (100mcg), Symbicort (80mcg)), to medium dose (Advair Diskus (250mcg), Advair HFA (115mcg), AirDuo (113mcg)) and high dose (Advair Diskus (500mcg), Advair HFA (230mcg), AirDuo (232mcg), Breo (200mcg), Dulera (200mcg), Symbicort (160mcg)).	Inhaled Corticosteroid/Long-acting Beta-agonist (NonTio Group) n=31 Participants Low dose ICS/LABA to medium/high dose ICS/LABA or from baseline medium dose ICS/LABA to high dose ICS/LABA or an additional prescription/refill of high-dose ICS/LABA following the first prescription of baseline high dose ICS/LABA within the study period. Advair Diskus, Advair HFA, AirDuo, Breo, Dulera or Symbicort were used for the ICS/LABA therapy from low dose (Advair Diskus (100mcg), Advair HFA (45mcg), AirDuo (55mcg), Breo (100mcg), Dulera (100mcg), Symbicort (80mcg)), to medium dose (Advair Diskus (250mcg), Advair HFA (115mcg), AirDuo (113mcg)) and high dose (Advair Diskus (500mcg), Advair HFA (230mcg), AirDuo (232mcg), Breo (200mcg), Dulera (200mcg), Symbicort (160mcg)).
Change in Asthma Control Test (ACT) Score at Baseline and in the Follow up Period	15.65 Score on a scale Standard Deviation 7.0	16.16 Score on a scale Standard Deviation 5.3

Adverse Events

Tiotropium Respimat® (Tio Group)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Inhaled Corticosteroid/Long-acting Beta-agonist (NonTio Group)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
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