Effects of Spiolto® Respimat® (Tiotropium/Olodaterol) on Cardiac Function in Hyperinflated COPD Subjects

NCT04231214 | Completed Phase 4

• 1 other identifier: 19-01 SPIOMI
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to examine the effect of a combined LABA/LAMA treatment with olodaterol/tiotropium on small airway function, autonomic nervous system and cardiac function in COPD. The main objective is to study the acute effect of dual bronchodilation with olodaterol/tiotropium on cardiac function measured by MRI. This work is unique as it assesses the effects of Spiolto® Respimat® on the left-ventricular end-diastolic volume and muscle sympathetic nerve activity, two endpoints relevant for cardiovascular disease. Furthermore, the study concept introduces exhaled particle analysis as a measure for small airway function, thus offering the opportunity for a mechanistic link between airway openness, hyperinflation, and cardiac function.

Conditions

Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (1)

• Change from baseline in left ventricular enddiastolic volume index (LVEDVi) after single dose of Spiolto® Respimat® versus nebulized saline

  Left ventricular enddiastolic volume index (LVEDVi) is a measurement of the volume of blood in the heart's left ventricular chamber at the end of the chamber's filling with blood and will be determined as measured by MRI

  Day -8 (baseline), Day 1, Day 9, Day 24

Secondary Outcomes (15)

• Channge from baseline in left ventricular enddiastolic volume index (LVEDVi) multiple doses of Spiolto® Respimat® versus nebulized saline

  Day 24

• Muscle sympathetic nerve activity (MSNA) evaluated by microneurography as bursts/ 100 heart beats after single dose administration of Spiolto® Respimat® versus nebulized saline

  Day 1, Day 9

• Forced Expiratory Volume in one second expressed as percent of Vital Capacity [FEV1/VC%] at baseline, after single dose and multiple of Spiolto® Respimat® versus nebulized saline.

  Day -28, Day -8, Day 1, Day 9, Day 24

• Mid Forced Expiratory Flow 25/75 [MFEF 25/75, L/s] at baseline, after single dose and multiple of Spiolto® Respimat® versus nebulized saline.

  Day -28, Day -8, Day 1, Day 9, Day 24

• Peak Expiratory Flow 50 [PEF, L/s] at baseline, after single dose and multiple of Spiolto® Respimat® versus nebulized saline.

  Day -28, Day -8, Day 1, Day 9, Day 24

Study Arms (2)

Treatment sequence 1

EXPERIMENTAL

Spiolto® Respimat® on Day 1 0.9% nebulized saline on Day 9 Spiolto® Respimat® from Day 10 to Day 24

Drug: Olodaterol-Tiotropium

Treatment sequence 2

EXPERIMENTAL

0.9% nebulized saline on Day 1 Spiolto® Respimat® on Day 9 Spiolto® Respimat® from Day 10 to Day 24

Drug: Olodaterol-Tiotropium

Interventions

Olodaterol-Tiotropium DRUG

5µg Olodaterol and 5 µg Tiotropium via the soft mist inhaler Respimat®, administered once on Day 1 or Day 9 and daily from Day 10 to Day 24

Treatment sequence 1; Treatment sequence 2

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able and willing to give written informed consent.
• Subjects with stable COPD according to the current GOLD guidelines (GOLD 2018).
• Subjects with airflow limitation indicated by a post-bronchodilator FEV1 \<80% of the predicted normal value and a post-bronchodilator FEV1/FC\<0.7 at Visit 1. Post-bronchodilator refers to within 10-15 min after inhalation of 400 µg (4x100 µg) of salbutamol.
• Current or ex-smokers who have a smoking history of at least 10 pack years. (Ten pack-years are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years etc.)
• Hyperinflated subjects with RVol\>135% predicted as measured at Visit 1, before intake of salbutamol.

You may not qualify if:

• Any clinically relevant abnormal findings in physical examination, clinical chemistry, haematology, urinalysis, vital signs, lung function or ECG at screening visit, which, in the opinion of the investigator, may either put the subject at risk because of participation in the study or may influence the results of the study, or the subject's ability to participate in the study.
• Past or present disease, which as judged by the investigator, may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease (including but not confined to aneurysm, hypokalemia, decompensated heart failure or hypertrophic obstructive cardiomyopathy), malignancy, hepatic disease, renal disease, haematological disease, neurological disease, endocrine disease (including but not confined to thyrotoxicosis) or pulmonary disease other than COPD (including but not confined to tuberculosis, bronchiectasis, cystic fibrosis, pulmonary hypertension, sarcoidosis, interstitial lung disease or lung fibrosis).
• Use of other investigational drug (approved or unapproved) at the time of enrolment, or within 30 days or 5 half-lives prior to Visit 1, whichever is longer.
• History of drug or alcohol abuse.
• Risk of non-compliance with study procedures.
• Suspected inability to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study.
• History of an acute respiratory infection four weeks prior to Visit 1 and between Visit 1 and 3. These patients will not be eligible, but will be permitted to rescreened 4 weeks after the resolution of the respiratory tract infection.
• Subjects with conditions contraindicated for treatment with, or having a history of reactions/hypersensitivity to any of the following inhaled drugs, drugs of a similar class or any component thereof:
• anticholinergics
• long and short acting beta-2 agonists
• sympathomimetic amines
• Subjects with a history of long QT syndrome or whose QTcF (Fridericia method) measured at Visit 1 is prolonged (\>450 ms for males and \>470 ms for females). These subjects should not be re-screened.
• Subjects who have clinically significant cardiovascular abnormalities, which could interfere with the assessment of the study treatment (such as but not limited to cardiac arrhythmias, heart failure with left ventricular ejection fraction \< 40 % as determined by MRI scan at Visit 2, unstable ischemic heart disease, NYHA Class III/IV left ventricular failure, history of myocardial infarction 6 months prior to Visit 1 or uncontrolled hypertension)
• Subjects with a known history or current atrial fibrillation to be confirmed by ECG at Visit 1.
• Subjects with pacemaker or bypass.

Sponsors & Collaborators

• Fraunhofer-Institute of Toxicology and Experimental Medicine: lead
• Boehringer Ingelheim: collaborator

Study Sites (1)

Fraunhofer ITEM

Hanover, Lower Saxony, 30625, Germany

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

tiotropium-olodaterol

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Staff at study site and data analysts are blinded for the primary endpoint (acute effects of Spiolto® Respimat® on cardiac function)
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Spiolto® Respimat® or nebulized 0.9 % saline on Day 1 and Day 9, followed by two weeks open label self-administration of Spiolto® Respimat®

Study Record Dates

• First Submitted: January 9, 2020
• First Posted: January 18, 2020
• Study Start: January 28, 2020
• Primary Completion: April 18, 2023
• Study Completion: April 18, 2023
• Last Updated: April 26, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)