Effects of Dual Bronchodilator Treatment on Cardiopulmonary Interactions in COPD

NCT03425617 | Completed Phase 4

• 1 other identifier: 6018318
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The deleterious consequences of lung hyperinflation seem not to be restricted to the respiratory system in patients with chronic obstructive pulmonary disease (COPD). Cardiac function, in particular, is strongly influenced by changes in lung volumes and intra-thoracic pressures. In this context, strategies to reduce lung hyperinflation and the work of breathing can positively impact upon cardiac output and blood flow redistribution to peripheral muscles in these patients. There is growing evidence that combination of bronchodilators of different classes is an efficacious and safe strategy for further improving airflow obstruction and hyperinflation in patients with more advanced COPD. Therefore, we aim to investigate that, compared with placebo, a novel LABA/LAMA fixed combination (tiotropium 5 mcg plus olodaterol 5 mcg via Respimat® (Inspiolto®) (TIO/OLO) would decrease lung volumes at rest and during exercise, thereby improving: 1) central and peripheral hemodynamics and 2) arterial oxygenation, with positive consequences on skeletal muscle oxygenation and exercise tolerance in hyperinflated patients with moderate to very severe COPD.

Conditions

Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (1)

• Blood Flow Index (BFI)

  Near infrared spectroscopy (NIRS)-derived muscle ICG difference divided by the rise time from 10 to 90% of peak.

  1 day

Secondary Outcomes (6)

• Cardiac output

  1 day

• Muscle oxygenation

  1 day

• Tlim

  1 day

• Exercise dyspnea

  1 day

• Inspiratory capacity

  1 day

Study Arms (2)

Tiotropium + Olodaterol first

EXPERIMENTAL

tiotropium 5 mcg plus olodaterol 5 mcg via Respimat® single dose in Visit 3 followed by PLACEBO via Respimat® single dose in Visit 4

Drug: Tiotropium + Olodaterol; Other: PLACEBO

PLACEBO FIRST

EXPERIMENTAL

Placebo via Respimat® single dose in Visit 3 followed bytiotropium 5 mcg plus olodaterol 5 mcg via Respimat® single dose in Visit 4

Drug: Tiotropium + Olodaterol; Other: PLACEBO

Interventions

Tiotropium + Olodaterol DRUG

tiotropium 5 mcg plus olodaterol 5 mcg via Respimat® single dose

Also known as: INSPIOLTO®

PLACEBO FIRST; Tiotropium + Olodaterol first

PLACEBO OTHER

PLACEBO via Respimat® single dose

PLACEBO FIRST; Tiotropium + Olodaterol first

Eligibility Criteria

• Age: 50 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥50 years;
• Male or female gender;
• Long-term history of active smoking;
• Signs and symptoms of COPD with adequate treatment according to the GOLD recommendations for at least 3 months (1);
• A modified MRC dyspnea score ≥2 or a Baseline Dyspnea Index ≤8;
• Resting lung hyperinflation as demonstrated by inspiratory capacity \<80% predicted or functional residual capacity \>120% predicted at Visit 1;
• Objective evidence of dynamic hyperinflation (a decrease in inspiratory capacity from rest \>200 mL)(24,25) and peak exercise dyspnea (breathing discomfort) ≥ leg discomfort scores during the incremental cardiopulmonary exercise test at Visit 1;
• A positive "volume" response (≥200 mL increase in inspiratory capacity) to a bronchodilator (400μg salbutamol) at Visit 1
• Ability to perform all study procedures and provide/sign informed consent.

You may not qualify if:

• Asthma or other concomitant pulmonary disease;
• Use of oral steroids in the preceding month;
• Orthopedic/rheumatological limitation precluded cycling;
• Type I or non-controlled type II diabetes mellitus or other endocrine diseases;
• Unstable angina, life-threatening cardiac arrhythmias, use of an implantable defibrillator;
• Myocardial infarction within the previous 6 months;
• History of long QT syndrome (or prolonged corrected QT interval (\>450 ms during screening);
• Clinically significant ECG abnormality;
• History of exercise-induced syncope;
• Any contraindication for exercise testing;
• Inability to understand and cooperate with the procedures.

Sponsors & Collaborators

• Queen's University: lead
• Boehringer Ingelheim: collaborator

Study Sites (1)

Kingston General Hospital

Kingston, Ontario, k7l2v7, Canada

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 Officials

• J Alberto Neder, Prof

  Queen'sUniversity/Kingston General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical professor

Study Record Dates

• First Submitted: February 1, 2018
• First Posted: February 7, 2018
• Study Start: January 1, 2017
• Primary Completion: June 30, 2018
• Study Completion: June 30, 2018
• Last Updated: February 5, 2019

Record last verified: 2019-02

Locations

CA (1)