Acute Effect of Aclidinium on Hyperinflation and Ventilation Inhomogeneity in Severe COPD Patients

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title: Acute Effect of Aclidinium on Hyperinflation and Lung Volume Distribution in Severe COPD Patients

Status Completed

Clinical Trial Summary

• Chronic Obstructive Pulmonary Disease (COPD) is characterized by lung hyperinflation and flow limitation. These physiopathological modifications are secondary to loss of elastic recoil and bronchial obstruction due to emphysema.

• The cornerstone of COPD treatment is represented by inhaled beta-2 agonists and anticholinergics. The molecules of the latter classes can be characterized by short lasting action (few hours), long acting action (12 hours) or ultra long acting duration of action (24 hours).

• For years the only anticholinergic (or antimuscarinic) drug other than those used by aerosol, was Tiotropium Bromide. Recently two new antimuscarinic agents have been launched on the market: glycopyrronium bromide (once daily) and aclidinium (twice daily).

• The Single Breath Nitrogen Test is capable of identifying the pulmonary closing volume. The part of the curve that reflects lung ventilation inhomogeneity is the slope of phase III

• For COPD patients, the most important characteristic for an inhalatory drug is a prompt action in order to give a quick relief from respiratory symptoms, in particular dyspnoea.

• The objective of this study is to study the acute action of glycopyrronium and aclidinium in terms of reduction of hyperinflation, pulmonary specific resistances, lung volume distribution and dyspnoea at rest in severe COPD patients.

• To our knowledge no study has explored these aspects before.

Clinical Trial Description

Chronic Obstructive Pulmonary Disease (COPD) is a disease characterized by progressive and evolutionary physiopathological changes that are responsible for the developing of respiratory symptoms, disability, poor quality of life and morbidity. These changes are secondary to parenchymal disruption and chronic bronchiolar inflammation in major part due to cigarette smoke.

Lung architectural derangement and loss of elastic recoil secondary to emphysema together with decreased internal bronchiolar lumen due to mucosal chronic inflammation are responsible for bronchial obstruction, flow limitation and lung hyperinflation. All these features bring to exertional dyspnoea, chronic cough and sputum and so decreased activeness in daily life activities.

The Single Breath Nitrogen Washout Test (SBN2) is one of the test that more adequately can catch the modifications of small airways and their premature collapse called closing volume (CV). Together with CV the test reflects pulmonary ventilation inhomogeneity through the slope of the so called phase III (a plateau line of nitrogen concentration that is steeper the bigger the ventilation inhomogeneity). In literature the effects of COPD inhalatory treatments on this modifications and on hyperinflation were until today poorly analysed. Recently some new anticholinergic molecules were developed, in particular Aclidinium Bromide and Glycopyrronium Bromide, and there is no trace of such evaluation in medical literature with those new inhalatory drugs.

The study of the acute effects of these drugs on lung mechanics are mandatory because the quicker the effects, the faster the patient's dyspnoea relief.

The study will comprise a first enrollment visit and then the suitable subjects will undergo a pharmacological washout of 72 hours from any inhalatory drug except from Salbutamol.

Then the patients will be randomised to be given Glycopyrronium Bromide 44 mcg (and matched Aclidinium Bromide 322 mcg placebo) or Aclidinium Bromide 322 mcg (and matched Glycopyrronium Bromide 44 mcg placebo) (Day 1) with a double dummy scheme.

At day 1 the pre-dose (baseline) evaluation consists of:

• body plethysmography (with residual volume and specific resistances evaluation),

• arterial blood gas analysis (partial pressure of oxygen and carbon dioxide evaluation),

• SBN2

• Visual Analogic Scale for Dyspnoea (VAS scale) evaluation

• Diffusion Lung Capacity for Carbon Monoxide with Single Breath method (DLCO). These tests will be repeated after 5, 15, 30, 60 and 180 minutes after study drug inhalation. DLCO and arterial blood gas analysis will be performed only at baseline and after 180 minutes after study drug inhalation.

After day 1 all the patients will undergo another period of inhalatory therapy washout of 72 hours (only rescue Salbutamol spray permitted).

After the second pharmacological washout the patients will undergo the crossing over. The ones who were given Aclidinium Bromide will assume Glycopyrronium Bromide and vice versa (Day 2) always in double dummy conditions.

At Day 2 all the patients will undergo the same evaluation as in day 1. At day 1 and day 2 the study drugs with the two different devices (active drug + placebo) will be given to the patients by medical personnel not involved in the performing of any of the tests of day 1 and 2, in order to maintain the double blind conditions. ;

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

• NCT number: NCT02181023
• Study type: Interventional
• Source: University of Milan
• Status: Completed
• Phase: Phase 4
• Start date: June 2014
• Completion date: October 2014