Clinical trial NCT04994574: Effects of Tiotropium/Olodaterol on Cardio-pulmonary Exercise Capacity in Patients With Hyperinflated Chronic Obstructive Pulmonary Disease [ACHIEVE]
Official title: Effects of Tiotropium/Olodaterol on Cardio-pulmonary Exercise Capacity in Patients With Hyperinflated Chronic Obstructive Pulmonary Disease [ACHIEVE]
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Chronic Obstructive Pulmonary Disease
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2021-08-06
Enrollment: 44
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: \[Background\] Hyperinflation caused by increased airflow limitation and emphysema change commonly accompanies dyspnea, which leads to inactivity, reducing exercise capacity, and deconditioning. Hyperinflation in COPD is also associated with decreased left and right end-diastolic volume and stroke volume, and cardiac output.

Previous studies investigated effects of ICS/LABA or LABA/LAMA versus placebo on cardiac function in patients with COPD and lung hyperinflation. However, there are not evidences for effects of LABA/LAMA on cardio-pulmonary exercise capacity.

Cardiopulmonary exercise testing (CPET) is an exercise stress test with concomitant expired gas analysis, which provides objective parameters of functional capacity. Since CPET can assess integrated exercise responses of cardiopulmonary, vascular, and skeletomuscular systems, it can reveal abnormalities that are not apparent in a resting state. Moreover, change in oxygen consumption during exercise and anaerobic threshold can be evaluated.

The investigators would like to investigate change in cardio-pulmonary exercise capacity via CPET before and after tiotropium/olodaterol inhalation in COPD patients with hyperinflation, which is the first clinical study. Association between change in cardio-pulmonary exercise capacity with function of heart and lung would be further evaluated with cardiac magnetic resonance (CMR) and lung function.

The in investigators expect to enhance cardio-pulmonary exercise capacity though the improvement in cardiac and pulmonary function with tiotropium/olodaterol inhalation. This result would provide evidence to encourage to treat with dual bronchodilators in COPD patients with hyperinflation.

\[Study objectives\] To investigate and compare the bronchodilator effect of tiotropium/olodaterol on cardio-pulmonary exercise capacity in hyperinflated COPD patients

\[Study design\] Prospective, single-center, one-arm clinical study After using the tiotropium/olodaterol inhaler for 4weeks, the investigators will compare pre- and post- cardio-pulmonary exercise capacity, cardiac function, lung function, symptoms and quality of life

\[Statistic methods\] For continuous variables, data will be presented as median, minimum, maximum with standard deviation (95% confidence intervals). For categorical variables, data will be presented as percentage (95% confidence intervals). Paired t-test for continuous variables and chi-squared test for categorical variables will be performed to compare the difference in results before and after inhalation of the tiotropium/olodaterol inhaler.

This is a pilot study; therefore, sample size cannot be calculated by power analysis, because of the absence of any data in the literature that could be reviewed. A sample size is expected to be 40 patients. When the drop-out rate 10% is considered, final sample size is expected to be 44.


Eligibility criteria: Inclusion Criteria:

1. The person who voluntarily signed the consent form
2. Adults over 40 years of age
3. Patients who diagnosed with COPD
4. Patients with smoking history of 10 packs or more
5. Patients who are taking or in need of tiotropium/olodaterol inhaler for the treatment of COPD
6. Patients in a clinically stable state within 3 months of screening
7. Patients who confirmed FEV1/FVC \< 0.7 and FEV1 \<80% after using bronchodilator
8. Patients who confirmed FRC \> 125%
9. Patients who confirmed mMRC \> 2

Exclusion Criteria:

1. Patients with a history of asthma
2. Patients with asthma- COPD overlap
3. Patients with serious disease other than COPD
4. Patients with unstable or life-threatening cardiac arrhythmias
5. Patients hospitalized for heart failure or myocardial infarction within 1 year of screening
6. Patients with systolic ejection fraction less than 40%
7. Patients with unstable ischemic heart disease
8. Patients receiving regular oxygen therapy for 1hour or more per day
9. Others who are difficult to participate in the research under judgment of the investigation

Primary outcomes:
measure: Change of maximum oxygen consumption
timeFrame: At 4 weeks
Secondary outcomes:
measure: Change in cardiopulmonary exercise test results after 4 weeks compared to baseline
timeFrame: At 4 weeks
measure: Change in cardiac MRI results after 4 weeks compared to baseline
timeFrame: At 4 weeks
measure: Change in echocardiography results after 4 weeks compared to baseline
timeFrame: At 4 weeks
measure: Change in spirometry results after 4 weeks compared to baseline
timeFrame: At 4 weeks
measure: Change in questionnaire evaluation and quality of life (CAT score) after 4 weeks compared to baseline
timeFrame: At 4 weeks
measure: Change in questionnaire evaluation and quality of life (mMRC score) after 4 weeks compared to baseline
timeFrame: At 4 weeks
measure: Change in questionnaire evaluation and quality of life (BDI score) after 4 weeks compared to baseline
timeFrame: At 4 weeks
measure: Change in questionnaire evaluation and quality of life (TDI score) after 4 weeks compared to baseline
timeFrame: At 4 weeks
measure: Change in serologic cardiac biomarkers after 4 weeks compared to baseline
timeFrame: At 4 weeks
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
Study officials:
affiliation: Severance Hospital, Yonsei University Health System
name: Ji Ye Jung
role: PRINCIPAL_INVESTIGATOR
References:
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