Trial Outcomes & Findings for Tiotropium (18mcg) in Chronic Obstructive Pulmonary Disease (COPD) Patients With a Respiratory Infection (NCT NCT01483625)

NCT ID: NCT01483625

Last Updated: 2014-06-09

Results Overview

The primary endpoint was trough forced expiratory volume in 1 second (FEV1) after 12 weeks on study drug. Trough forced expiratory volume in 1 second (FEV1)was defined as the FEV1 measurement prior to the next dosing of study drug and approximately 24 hours after the last inhalation of study drug.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 140 participants
• Primary outcome timeframe: 12 weeks
• Results posted on: 2014-06-09

Participant Flow

In this 12-week, randomised, double-blind, placebo-controlled, parallel group, multi-center Phase IV trial in chronic obstructive pulmonary disease (COPD), 140 patients were randomised to either Tiotropium 18 mcg or Placebo. Sixty eight (68) patients received Tiotropium 18 mcg and seventy two (72) patients received Placebo.

Participant milestones

Measure	Placebo placebo - Placebo Inhalation capsule, HandiHaler®	Tiotropium 18 mcg active - Tiotropium bromide Inhalation capsule 18 mcg, HandiHaler®
Overall Study STARTED	72	68
Overall Study COMPLETED	68	66
Overall Study NOT COMPLETED	4	2

Reasons for withdrawal

Measure	Placebo placebo - Placebo Inhalation capsule, HandiHaler®	Tiotropium 18 mcg active - Tiotropium bromide Inhalation capsule 18 mcg, HandiHaler®
Overall Study Adverse Event	1	1
Overall Study Refused to continue medication	2	1
Overall Study Due to other reason	1	0

Baseline Characteristics

Tiotropium (18mcg) in Chronic Obstructive Pulmonary Disease (COPD) Patients With a Respiratory Infection

Baseline characteristics by cohort

Measure	Placebo n=72 Participants placebo - Placebo Inhalation capsule, HandiHaler®	Tiotropium 18mcg n=68 Participants active - Tiotropium bromide Inhalation capsule 18 mcg, HandiHaler®	Total n=140 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	59 Participants n=5 Participants	53 Participants n=7 Participants	112 Participants n=5 Participants
Age, Categorical >=65 years	13 Participants n=5 Participants	15 Participants n=7 Participants	28 Participants n=5 Participants
Age, Continuous	56.8 years STANDARD_DEVIATION 8.7 • n=5 Participants	59.2 years STANDARD_DEVIATION 8.5 • n=7 Participants	58.0 years STANDARD_DEVIATION 8.7 • n=5 Participants
Sex: Female, Male Female	34 Participants n=5 Participants	43 Participants n=7 Participants	77 Participants n=5 Participants
Sex: Female, Male Male	38 Participants n=5 Participants	25 Participants n=7 Participants	63 Participants n=5 Participants
Trough forced expiratory value (FEV1)	1.75 Litre STANDARD_DEVIATION 0.65 • n=5 Participants	1.56 Litre STANDARD_DEVIATION 0.61 • n=7 Participants	1.65 Litre STANDARD_DEVIATION 0.64 • n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: Treated Set (TS) with non missing FEV1 data.

The primary endpoint was trough forced expiratory volume in 1 second (FEV1) after 12 weeks on study drug. Trough forced expiratory volume in 1 second (FEV1)was defined as the FEV1 measurement prior to the next dosing of study drug and approximately 24 hours after the last inhalation of study drug.

Outcome measures

Measure	Placebo n=67 Participants placebo - Placebo Inhalation capsule, HandiHaler®	Tiotropium 18 mcg n=67 Participants active - Tiotropium bromide Inhalation capsule 18 mcg, HandiHaler®
Trough FEV1 After 12 Weeks on Study Drug	0.0378 Litre Standard Error 0.0383	0.0947 Litre Standard Error 0.0390

SECONDARY outcome

Timeframe: 12 weeks

Population: TS with non missing EXACT-PRO data.

Time to recovery was assessed with the EXACT-PRO questionnaire tool. The EXACT-PRO was designed to collect data to quantify frequency, severity, and duration of exacerbations in patients with COPD including the onset of and the recovery from COPD exacerbations.

The EXACT-PRO is a 14-item questionnaire. Each attribute or item was assessed on a five- or six-point ordinal scale and summed to yield a total score that was converted to a 0-100 scale, with higher scores indicating a more severe health state or exacerbation.

The EXACT-PRO was answered by the patients on a daily basis in the evening.

Outcome measures

Measure	Placebo n=70 Participants placebo - Placebo Inhalation capsule, HandiHaler®	Tiotropium 18 mcg n=67 Participants active - Tiotropium bromide Inhalation capsule 18 mcg, HandiHaler®
Time to Recovery From Acute Respiratory Symptoms	48.44 units on a scale Standard Deviation 12.33	47.86 units on a scale Standard Deviation 11.95

SECONDARY outcome

Timeframe: 12 weeks

Population: TS with non missing FVC data.

The trough Forced Vital Capacity (FVC) was defined as the FVC measurement prior to the next dosing of study drug and approximately 24 hours after the last inhalation of study drug.

Outcome measures

Measure	Placebo n=67 Participants placebo - Placebo Inhalation capsule, HandiHaler®	Tiotropium 18 mcg n=67 Participants active - Tiotropium bromide Inhalation capsule 18 mcg, HandiHaler®
Trough FVC (in Litres) at 12 Weeks	3.1537 Litres Standard Deviation 0.9772	2.9097 Litres Standard Deviation 0.9675

SECONDARY outcome

Timeframe: 4 weeks

Population: Responder defined by \>= 20% improvement. TS with non missing responder data.

Responder status was determined at each clinic visit. The number and percentage of subjects in each of the following 3 classes were presented:

• Subject recovered without change of therapy (subjects who received an additional course of antibiotics and/or systemic corticosteroids starting after Visit 1 were not included).
• Subject recovered but had a change in therapy (subject received an additional course of antibiotics and/or systemic corticosteroids starting after Visit 1).
• Subject did not recover.

Outcome measures

Measure	Placebo n=70 Participants placebo - Placebo Inhalation capsule, HandiHaler®	Tiotropium 18 mcg n=67 Participants active - Tiotropium bromide Inhalation capsule 18 mcg, HandiHaler®
Responder Status at Week 4 Clinic Visit Week 4: Responder without therapy change	38 participants	39 participants
Responder Status at Week 4 Clinic Visit Week 4: Responder with changed therapy	1 participants	2 participants
Responder Status at Week 4 Clinic Visit Week 4: Non-responder	31 participants	26 participants

SECONDARY outcome

Timeframe: 12 weeks

Population: TS with non missing responder data at week 12. Responder defined by \>= 20% improvement. .

Responder status was determined at each clinic visit. The number and percentage of subjects in each of the following 3 classes were presented:

• Subject recovered without change of therapy (subjects who received an additional course of antibiotics and/or systemic corticosteroids starting after Visit 1 were not included).
• Subject recovered but had a change in therapy (subject received an additional course of antibiotics and/or systemic corticosteroids starting after Visit 1).
• Subject did not recover.

Outcome measures

Measure	Placebo n=66 Participants placebo - Placebo Inhalation capsule, HandiHaler®	Tiotropium 18 mcg n=58 Participants active - Tiotropium bromide Inhalation capsule 18 mcg, HandiHaler®
Responder Status at Week 12 Clinic Visit Week 12: Responder without therapy change	34 participants	34 participants
Responder Status at Week 12 Clinic Visit Week 12: Responder with changed therapy	0 participants	0 participants
Responder Status at Week 12 Clinic Visit Week 12: Non-responder	32 participants	24 participants

SECONDARY outcome

Timeframe: 12 weeks

Population: TS with non missing rescue medication use.

Daily rescue albuterol use was recorded in the diary in response to the following question: How many puffs of rescue medication did you use during the last 24 hours? The weekly rescue medication use was derived by summing the daily uses over the 12 weeks and dividing this total by 12 weeks.

Outcome measures

Measure	Placebo n=72 Participants placebo - Placebo Inhalation capsule, HandiHaler®	Tiotropium 18 mcg n=68 Participants active - Tiotropium bromide Inhalation capsule 18 mcg, HandiHaler®
Weekly Rescue Medication Use Over the 12 Weeks of Study	17.0 puffs Standard Deviation 18.9	12.9 puffs Standard Deviation 16.6

Adverse Events

Placebo

Serious events: 3 serious events

Other events: 8 other events

Deaths: 0 deaths

Tiotropium 18 mcg

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=72 participants at risk placebo - Placebo Inhalation capsule, HandiHaler®	Tiotropium 18 mcg n=68 participants at risk active - Tiotropium bromide Inhalation capsule 18 mcg, HandiHaler®
Cardiac disorders Cardiac failure congestive	1.4% 1/72 • 12 weeks	0.00% 0/68 • 12 weeks
Cardiac disorders Cardiomyopathy	1.4% 1/72 • 12 weeks	0.00% 0/68 • 12 weeks
Gastrointestinal disorders Colitis	0.00% 0/72 • 12 weeks	1.5% 1/68 • 12 weeks
General disorders Chest pain	0.00% 0/72 • 12 weeks	1.5% 1/68 • 12 weeks
Infections and infestations Gastroenteritis	0.00% 0/72 • 12 weeks	1.5% 1/68 • 12 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	1.4% 1/72 • 12 weeks	0.00% 0/68 • 12 weeks
Nervous system disorders Syncope	1.4% 1/72 • 12 weeks	0.00% 0/68 • 12 weeks
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	1.4% 1/72 • 12 weeks	1.5% 1/68 • 12 weeks
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	2.8% 2/72 • 12 weeks	2.9% 2/68 • 12 weeks

Other adverse events

Measure	Placebo n=72 participants at risk placebo - Placebo Inhalation capsule, HandiHaler®	Tiotropium 18 mcg n=68 participants at risk active - Tiotropium bromide Inhalation capsule 18 mcg, HandiHaler®
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	11.1% 8/72 • 12 weeks	8.8% 6/68 • 12 weeks

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

Results disclosure agreements

• Principal investigator is a sponsor employee Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
• Publication restrictions are in place

Restriction type: OTHER