Trial Outcomes & Findings for Blacks and Exacerbations on Long Acting Beta Agonists (LABA) vs. Tiotropium (BELT) (NCT NCT01290874)

NCT ID: NCT01290874

Last Updated: 2018-03-30

Results Overview

We summarize the survival experience using mean number of exacerbations/person-year and compare it using the log-rank test comparing kaplan-meier survival curve.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1070 participants
• Primary outcome timeframe: evaluated monthly (on average) via questionnaire for 12 months
• Results posted on: 2018-03-30

Participant Flow

Initial enrollment began March 30, 2011 at the Asthma Research Center at Brigham and Women's Hospital. Subjects were recruited with print advertisements, internet postings, physician referrals, and by contacting patients in databases who asked to be contacted for studies.

Subjects on combination ICS/LABA were switched to equivalent-dose ICS monotherapy at the same time they were assigned to the Tiotropium vs. LABA arm of the study.

Participant milestones

Measure	Tiotropium Tiotropium: Tiotropium bromide 18 mcg once daily for one year of treatment.	Salmeterol or Formoterol Long acting beta agonists (Serevent, Foradil) are the standard treatments for moderate asthma. The efficacy of Tiotropium will be compared to this standard. Salmeterol: Salmeterol 50 mcg twice daily for one year of treatment. Formoterol: Formoterol 12 mcg twice daily for one year
Overall Study STARTED	532	538
Overall Study COMPLETED	122	134
Overall Study NOT COMPLETED	410	404

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Blacks and Exacerbations on Long Acting Beta Agonists (LABA) vs. Tiotropium (BELT)

Baseline characteristics by cohort

Measure	Tiotropium n=532 Participants Tiotropium bromide will be evaluated as a treatment for asthma. Tiotropium: Tiotropium bromide 18 mcg once daily for one year of treatment.	Salmeterol or Formoterol n=538 Participants Long acting beta agonists (Serevent, Foradil) are the standard treatments for moderate asthma. The efficacy of Tiotropium will be compared to this standard. Salmeterol: Salmeterol 50 mcg twice daily for one year of treatment. Formoterol: Formoterol 12 mcg twice daily for one year	Total n=1070 Participants Total of all reporting groups
Age, Continuous	45.2 years STANDARD_DEVIATION 12.6 • n=93 Participants	45.1 years STANDARD_DEVIATION 12.6 • n=4 Participants	45.15 years STANDARD_DEVIATION 12.6 • n=27 Participants
Sex: Female, Male Female	405 Participants n=93 Participants	408 Participants n=4 Participants	813 Participants n=27 Participants
Sex: Female, Male Male	127 Participants n=93 Participants	130 Participants n=4 Participants	257 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	31 Participants n=93 Participants	36 Participants n=4 Participants	67 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	501 Participants n=93 Participants	502 Participants n=4 Participants	1003 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	532 Participants n=93 Participants	538 Participants n=4 Participants	1070 Participants n=27 Participants
Race (NIH/OMB) White	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants

PRIMARY outcome

Timeframe: evaluated monthly (on average) via questionnaire for 12 months

Population: intention-to-treat

We summarize the survival experience using mean number of exacerbations/person-year and compare it using the log-rank test comparing kaplan-meier survival curve.

Outcome measures

Measure	Tiotropium n=532 Participants Tiotropium: Tiotropium bromide 18 mcg once daily for one year of treatment.	Salmeterol or Formoterol n=538 Participants Long acting beta agonists (Serevent, Foradil) are the standard treatments for moderate asthma. The efficacy of Tiotropium will be compared to this standard. Salmeterol: Salmeterol 50 mcg twice daily for one year of treatment. Formoterol: Formoterol 12 mcg twice daily for one year
Time to Asthma Exacerbation (Mean Number of Exacerbations/Person-year)	0.37 event per person-year Interval 0.32 to 0.43	0.42 event per person-year Interval 0.36 to 0.48

SECONDARY outcome

Timeframe: from baseline to 12 months

Population: 255 and 253 participants are missing data on change in FEV1 in the Tiotropium and Salmeterol or Formoterol arms, respectively.

Average change in lung function (FEV1) evaluated by spirometry per participant over 12 months

Outcome measures

Measure	Tiotropium n=277 Participants Tiotropium: Tiotropium bromide 18 mcg once daily for one year of treatment.	Salmeterol or Formoterol n=285 Participants Long acting beta agonists (Serevent, Foradil) are the standard treatments for moderate asthma. The efficacy of Tiotropium will be compared to this standard. Salmeterol: Salmeterol 50 mcg twice daily for one year of treatment. Formoterol: Formoterol 12 mcg twice daily for one year
Change in FEV1	-0.018 liters Interval -0.047 to 0.012	0.003 liters Interval -0.026 to 0.031

SECONDARY outcome

Timeframe: from baseline to 12 months

Population: 334 and 326 participants are missing data on ACQ in the Tiotropium and Salmeterol or Formoterol arms, respectively.

Average Change in Asthma Control Score Per Participant Over 12 Months Using the Asthma Control Questionnaire (ACQ).

The ACQ has six questions regarding symptoms, rescue short-acting β-agonist use and one about FEV1 % predicted. A 7-point scale (0 = no impairment, 6 = maximum impairment) is used for each question and the ACQ score is the mean value of these questions - hence between 0 (totally controlled) and 6 (severely uncontrolled).

Outcome measures

Measure	Tiotropium n=198 Participants Tiotropium: Tiotropium bromide 18 mcg once daily for one year of treatment.	Salmeterol or Formoterol n=212 Participants Long acting beta agonists (Serevent, Foradil) are the standard treatments for moderate asthma. The efficacy of Tiotropium will be compared to this standard. Salmeterol: Salmeterol 50 mcg twice daily for one year of treatment. Formoterol: Formoterol 12 mcg twice daily for one year
Change in Asthma Control Questionnaire (ACQ)	-0.70 units on a scale Interval -0.81 to -0.6	-0.66 units on a scale Interval -0.77 to -0.55

SECONDARY outcome

Timeframe: from baseline to 12 months

Population: 242 and 239 participants are missing data on AQLQ in the Tiotropium and Salmeterol or Formoterol arms, respectively.

Average Change in Asthma Quality of Life Score Per Participant Over 12 Months Using the Asthma Quality of Life Questionnaire (AQLQ).

The AQLQ has 32 questions in four domains (symptoms, activity limitation, emotional function, and environmental stimuli) and measures the functional problems that are troublesome to individuals with asthma. Symptoms (11 items), Activity Limitation (12 items, 5 of which are individualized), Emotional Function (5 items), and Environmental Exposure (4 items); 7-point Likert scale (7 = not impaired at all - 1 = severely impaired); scores range 1-7, with higher scores indicating better quality of life.

Outcome measures

Measure	Tiotropium n=290 Participants Tiotropium: Tiotropium bromide 18 mcg once daily for one year of treatment.	Salmeterol or Formoterol n=299 Participants Long acting beta agonists (Serevent, Foradil) are the standard treatments for moderate asthma. The efficacy of Tiotropium will be compared to this standard. Salmeterol: Salmeterol 50 mcg twice daily for one year of treatment. Formoterol: Formoterol 12 mcg twice daily for one year
Change in Asthma Quality of Life (AQLQ)	1.00 units on a scale Interval 0.88 to 1.12	1.02 units on a scale Interval 0.9 to 1.14

SECONDARY outcome

Timeframe: from baseline to 12 months

Population: 257 and 265 participants are missing data on ASUI in the Tiotropium and Salmeterol or Formoterol arms, respectively.

Average Change in Asthma Symptom Utility Score Per Participant Over 12 Months Using the Asthma Symptom Utility Index (ASUI).

The ASUI is an 11-item preference-based outcome measure used in clinical trials and cost-effectiveness studies for asthma and is designed to assess the frequency and severity of cough, wheeze, dyspnea, nighttime awakenings, and side effects, weighted according to patient preferences.

4-point Likert scale to assess frequency (not at all, 1 to 3 days, 4 to 7 days, and 8 to 14 days) and severity (not applicable, mild, moderate and severe); scores range from 0 (worst possible symptoms) to 1 (no symptoms).

Outcome measures

Measure	Tiotropium n=275 Participants Tiotropium: Tiotropium bromide 18 mcg once daily for one year of treatment.	Salmeterol or Formoterol n=273 Participants Long acting beta agonists (Serevent, Foradil) are the standard treatments for moderate asthma. The efficacy of Tiotropium will be compared to this standard. Salmeterol: Salmeterol 50 mcg twice daily for one year of treatment. Formoterol: Formoterol 12 mcg twice daily for one year
Change in Asthma Symptom Utility Index (ASUI)	0.11 units on a scale Interval 0.09 to 0.13	0.10 units on a scale Interval 0.08 to 0.13

SECONDARY outcome

Timeframe: from baseline to 12 months

Population: The instrument used to collect data proved to be unreliable. The statistic for internal consistency demonstrated less than 30% internal consistency.

Average Change in Symptom-Free Days Per Participant Over 12 Months Using the Symptom-Free Day Questionnaire (SFDQ).

The asthma symptom free day questionnaire (SFDQ) quantifies the number of days with neither daytime nor nighttime asthma symptoms, nor awakenings due to asthma symptoms.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from baseline to 12 months

Population: 335 and 328 participants are missing data on rescue medication use in the Tiotropium and Salmeterol or Formoterol arms, respectively.

Average Change in Rescue Medication Use Per Participant Over 12 Months. Monthly questionnaires will evaluate the amount of rescue medication subjects have used on average, measured in puffs per day.

Outcome measures

Measure	Tiotropium n=197 Participants Tiotropium: Tiotropium bromide 18 mcg once daily for one year of treatment.	Salmeterol or Formoterol n=210 Participants Long acting beta agonists (Serevent, Foradil) are the standard treatments for moderate asthma. The efficacy of Tiotropium will be compared to this standard. Salmeterol: Salmeterol 50 mcg twice daily for one year of treatment. Formoterol: Formoterol 12 mcg twice daily for one year
Change in Rescue Medication Use	-0.92 units on a scale Interval -1.27 to -0.57	-0.97 units on a scale Interval -1.32 to -0.63

SECONDARY outcome

Timeframe: from baseline to 12 months

Population: Inadequate baseline data was collected so that the change in this variable could not be assessed.

Average Change in Moderate Asthma Deterioration Per Participant Over 12 Months. The definition of a moderate asthma deterioration should include one or more of the following: deterioration in symptoms, deterioration in lung function, or increased rescue bronchodilator use. These features should last for 2 days or more, but not be severe enough to warrant systemic corticosteroid use and/or hospitalization.

Outcome measures

Outcome data not reported

Adverse Events

Tiotropium

Serious events: 84 serious events

Other events: 338 other events

Deaths: 0 deaths

Salmeterol or Formoterol

Serious events: 69 serious events

Other events: 342 other events

Deaths: 0 deaths

Serious adverse events

Measure	Tiotropium n=532 participants at risk Tiotropium: Tiotropium bromide 18 mcg once daily for one year of treatment.	Salmeterol or Formoterol n=538 participants at risk Long acting beta agonists (Serevent, Foradil) are the standard treatments for moderate asthma. The efficacy of Tiotropium will be compared to this standard. Salmeterol: Salmeterol 50 mcg twice daily for one year of treatment. Formoterol: Formoterol 12 mcg twice daily for one year
Cardiac disorders Acute Myocardial Infarction	0.38% 2/532 • Number of events 2 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Cardiac disorders Angina Pectoris	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Cardiac disorders Angina Unstable	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Cardiac disorders Cardiac Disorder	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Cardiac disorders Cardiac Failure Congestive	0.56% 3/532 • Number of events 3 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.37% 2/538 • Number of events 2 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Cardiac disorders Cardiomyopathy	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Cardiac disorders Cardiopulmonary Failure	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Cardiac disorders Coronary Artery Disease	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Cardiac disorders Coronary Artery Occlusion	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Cardiac disorders Dysponea	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Cardiac disorders Myocardial Infarction	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Cardiac disorders Tachycardia	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.37% 2/538 • Number of events 2 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Endocrine disorders Goitre	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Eye disorders Vision blurred	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Gastrointestinal disorders Abdominal Distension	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Gastrointestinal disorders Abdominal Hernia	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Gastrointestinal disorders Abdominal Pain	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Gastrointestinal disorders Diarrhoea	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Gastrointestinal disorders Diverticulum Intestinal	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Gastrointestinal disorders Gastritis	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Gastrointestinal disorders Hiatus Hernia	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Gastrointestinal disorders Impaired Gastric Emptying	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Gastrointestinal disorders Rectal Haemorrhage	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Gastrointestinal disorders Small Intestinal Obstruction	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Gastrointestinal disorders Upper Gastrointestinal Haemorrhage	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
General disorders Chest Discomfort	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
General disorders Chest Pain	1.5% 8/532 • Number of events 8 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	1.1% 6/538 • Number of events 6 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
General disorders Non-cardiac chest pain	0.38% 2/532 • Number of events 2 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.37% 2/538 • Number of events 2 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
General disorders Oedema	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
General disorders Oedema Peripheral	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Hepatobiliary disorders Gallbladder Disorder	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Immune system disorders Anaphylactic Reaction	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Infections and infestations Appendicitis	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Infections and infestations Diverticulitis	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Infections and infestations Gastrointestinal bacterial infection	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Infections and infestations Localized Infection	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Infections and infestations Pyelonephritis	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Infections and infestations Sepsis	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Infections and infestations Urinary tract infection	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Infections and infestations Viral infection	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Infections and infestations Wound infection	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Injury, poisoning and procedural complications Incisional hernia	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Investigations Blood glucose increased	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Metabolism and nutrition disorders Dehydration	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Metabolism and nutrition disorders Diabetes mellitus	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.37% 2/538 • Number of events 2 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Musculoskeletal and connective tissue disorders Costochondritis	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Musculoskeletal and connective tissue disorders Pain in extremity	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial cancer	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Nervous system disorders Cerebral cyst	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Nervous system disorders Cerebrovascular accident	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Nervous system disorders Convulsion	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.37% 2/538 • Number of events 2 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Nervous system disorders Dizziness	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Nervous system disorders Dysarthria	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Nervous system disorders Headache	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Nervous system disorders Hemiparesis	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Nervous system disorders Hypoaesthesia	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Nervous system disorders Loss of consciousness	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Nervous system disorders Myelopathy	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Nervous system disorders Syncope	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Nervous system disorders Transient ischaemic attack	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Psychiatric disorders Depression	0.38% 2/532 • Number of events 2 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Psychiatric disorders Mental status change	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Renal and urinary disorders Nephrolithiasis	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Renal and urinary disorders Renal failure	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Renal and urinary disorders Renal failure acute	0.38% 2/532 • Number of events 2 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Reproductive system and breast disorders Menorrhagia	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Reproductive system and breast disorders Postmenopausal haemorrhage	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Respiratory, thoracic and mediastinal disorders Bronchitis	0.38% 2/532 • Number of events 2 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Respiratory, thoracic and mediastinal disorders Pneumonia	1.3% 7/532 • Number of events 7 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.93% 5/538 • Number of events 5 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Skin and subcutaneous tissue disorders Blister	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Vascular disorders Deep vein thrombosis	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Vascular disorders Hypertension	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Vascular disorders Hypertensive crisis	0.38% 2/532 • Number of events 2 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Vascular disorders Hypotension	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.37% 2/538 • Number of events 2 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Vascular disorders Vasculitis	0.00% 0/532 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.19% 1/538 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
General disorders Disease Progression	0.19% 1/532 • Number of events 1 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	0.00% 0/538 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Respiratory, thoracic and mediastinal disorders Asthma	5.6% 30/532 • Number of events 30 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	4.3% 23/538 • Number of events 23 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.

Other adverse events

Measure	Tiotropium n=532 participants at risk Tiotropium: Tiotropium bromide 18 mcg once daily for one year of treatment.	Salmeterol or Formoterol n=538 participants at risk Long acting beta agonists (Serevent, Foradil) are the standard treatments for moderate asthma. The efficacy of Tiotropium will be compared to this standard. Salmeterol: Salmeterol 50 mcg twice daily for one year of treatment. Formoterol: Formoterol 12 mcg twice daily for one year
General disorders Disease Progression	39.7% 211/532 • Number of events 211 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	37.7% 203/538 • Number of events 203 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.
Respiratory, thoracic and mediastinal disorders Asthma	23.9% 127/532 • Number of events 127 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.	25.8% 139/538 • Number of events 139 • Adverse events were reported from the time of patient enrollment to up to 18 months after study completion.

Additional Information

Dr. Elliot Israel

Brigham and Women's Hospital

Phone: 6177328201

Email: eisrael@partners.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place