Acute Effect of Pulmonary Desufflation on Cardiac Performance in COPD Patients

NCT01996124 | Completed Phase 4 DMC

• 1 other identifier: 902 CEC
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic Obstructive Pulmonary disease (COPD) is one of the major clinical entities that causes thousands of deaths every year all over the world and weights a lot on the health care system of every country in terms of direct and indirect costs. The physiopathological modifications that characterise COPD are represented by irreversible (sometimes partially reversible) airflow obstruction, and bronchiolar inflammation. Lungs that develop emphysema lack of elastic recoil and imply increased resistances and airflow obstruction due to loss of lung parenchyma and supporting elastic structures. All these modifications produce air trapping and so lung hyperinflation. The latter is precisely the cause of the symptoms and particularly dyspnoea which is often heavily perceived by COPD patients and that drives to the limitation of daily activities. Lung hyperinflation and the other alterations that occur in COPD imply gas retention and increase in pulmonary vascular resistances. Considering that the rib cage has limited elastic properties, the effects of gas trapping and lung parenchymal damage on mediastinum and particularly on heart mechanics is indisputable. Together with alveolar hypoxia, lung hyperinflation is responsible for the development, as the disease progresses, of the cor pulmonale. Tha latter causes pulmonary hypertension and increased mechanic load during right heart chambers contraction and relaxation. Those alterations may effect left heart chambers too. Airflow obstruction in COPD is usually treated by inhaled bronchodilators and corticosteroids. The main and most used bronchodilators are represented by beta 2 agonists (short, long and ultra-long acting) and anticholinergic inhalatory drugs, which can be also short, long and ultra long acting. Among ultra long acting beta 2 agonists, indacaterol is characterised by quick onset of action (5 minutes), and guarantees an effective bronchodilation duration of 24 hours. It is also known that it has an important effect on reducing lung hyperinflation decreasing residual volume and consequently allowing an increase of inspiratory capacity. The purpose of our study is to evaluate the effects of indacaterol on lung hyperinflation in COPD subjects of any stage and with lung air trapping, and the consequent potential effects on heart performance evaluated by cardiac trans thoracic echo color doppler.

Conditions

COPD; Hyperinflation; Right Cardiac Failure

Keywords

COPD; Pulmonary Hyperinflation; Ultra Long Acting Beta 2 Agonists; Cor Pulmonale; Cardiac performance

Outcome Measures

Primary Outcomes (1)

• Effect of the decrease of residual volume and functional residual capacity on right cardiac performance assessing E/A and E/e' parameters on the mitral, pulmonary and tricuspid valve anulus, telediastolic pulmonary gradient, and venous pulmonary flow.

  The right cardiac performance will be assessed throw trans-thoracic coor-doppler echocardiography. A trained technician will perform three echocardiographies at baseline, after 60 and 180 minutes after inhalation of indacaterol 150 mcg breezehaler. At every time point, after the echocardiographic assessment, a spirometric, plethysmographic and the lung diffusion for carbon monoxide test will be made in order to evaluate static and dynamic lung volumes.

  The assessment will be made at three different time points: 1) At baseline 2) sixty (60) minutes after indacaterol inhalation 3) a hundred eighty (180) minutes after indacaterol inhalation

Secondary Outcomes (5)

• Evaluation of interventricular septum motility modification

  The assessment will be made at three different time points: 1) At baseline 2) sixty (60) minutes after indacaterol inhalation 3) a hundred eighty (180) minutes after indacaterol inhalation

• Evaluation of cardiac left ventricular ejection fraction modifications

  The assessment will be made at three different time points: 1) At baseline 2) sixty (60) minutes after indacaterol inhalation 3) a hundred eighty (180) minutes after indacaterol inhalation

• Evaluation of right cardiac chambers kinetics modifications

  The assessment will be made at three different time points: 1) At baseline 2) sixty (60) minutes after indacaterol inhalation 3) a hundred eighty (180) minutes after indacaterol inhalation

• Evaluation of inspiratory capacity modifications

  A spirometric and plethysmographic assessment will be performed at three different time points: 1) At baseline 2) sixty (60) minutes after indacaterol inhalation 3) a hundred eighty (180) minutes after indacaterol inhalation

• Evaluation of specific airway resistances modifications

  A spirometric and plethysmographic assessment will be performed at three different time points: 1) At baseline 2) sixty (60) minutes after indacaterol inhalation 3) a hundred eighty (180) minutes after indacaterol inhalation

Study Arms (2)

Indacaterol

EXPERIMENTAL

Indacaterol Fumarate 150 mcg Breezehaler,Onbrez Novartis International AG, Basel Switzerland. Once daily.

Drug: Indacaterol Fumarate

Placebo

PLACEBO COMPARATOR

Placebo Breezehaler

Drug: Placebo

Interventions

Indacaterol Fumarate DRUG

150 mcg inhalation powder, hard capsules, once daily

Also known as: Onbrez Breezhaler (Novartis International AG, Basel Switzerland)

Indacaterol

Placebo DRUG

Fructose, dry inhalation powder, hard capsules via breezhaler

Also known as: Placebo, fructose 150 mcg via Breezhaler, inhalation powder

Placebo

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signature of informed consent
• COPD patients with age raging from 50 to 85 years old
• Patients with at least a history of COPD of one year
• COPD patients clinically stable in the last three months
• COPD subjects with FEV1 (Forced Expiratory Volume at one second)\<70% of predicted value
• FEV1/FVC (Forced Vital Capacity)\<88% (males) or \<89% (females) of LLN (Lower Levels of Normality)
• COPD former or active smokers with at least a smoking history of 20 pack years
• Residual Volume (RV) \>= 125% predicted value
• No Cardiac ultrasound signs of Cor Pulmonale

You may not qualify if:

• Acute Bronchial Exacerbation at recruitment
• Fertile women with age between 18 and 50 years old or with active period
• Pregnancy
• Subjects enrolled in other clinical trials or that have taken part in one of them in the month preceding the enrollment.
• FEV1/FVC more than 70% of predicted value in basal conditions
• FEV1 more than 70% of predicted value in basal conditions
• Residual Volume \< 125% predicted value
• Known deficit of alpha 1 antitrypsin
• Subjects that underwent a Lung Volume Reduction Surgery (LVRS)
• Subjects with known positivity to Human Immunodeficiency Virus (HIV)
• Misuse of alcool or drugs
• Lack of compliance in performing respiratory tests
• Subjects not capable to follow the study prescriptions because of psychic disorders or language problems.
• Long Term Oxygen Therapy with flows \> 6 litres per minute (l/min) at rest
• Cor Pulmonale

Sponsors & Collaborators

• University of Milan: lead
• Fondazione Salvatore Maugeri: collaborator

Study Sites (1)

Pneumologia Riabilitativa-Fondazione Maugeri-Istituto Scientifico di Milano- IRCCS

Milan, Milan, 20142, Italy

Location

Related Publications (2)

• Steiropoulos P, Papanas N, Nena E, Bouros D. Indacaterol: a new long-acting beta2-agonist in the management of chronic obstructive pulmonary disease. Expert Opin Pharmacother. 2012 May;13(7):1015-29. doi: 10.1517/14656566.2012.674513. Epub 2012 Apr 4.

  PMID: 22471750 BACKGROUND

• Barr RG, Bluemke DA, Ahmed FS, Carr JJ, Enright PL, Hoffman EA, Jiang R, Kawut SM, Kronmal RA, Lima JA, Shahar E, Smith LJ, Watson KE. Percent emphysema, airflow obstruction, and impaired left ventricular filling. N Engl J Med. 2010 Jan 21;362(3):217-27. doi: 10.1056/NEJMoa0808836.

  PMID: 20089972 BACKGROUND

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Pulmonary Heart Disease

Interventions

Fructose

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses

Study Officials

• Pierachille Santus, Md, PhD

  Università degli Studi di Milano-Pneumologia Riabilitativa-Fondazione Salvatore Maugeri-MILANO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Pulmonary Rehabilitation Unit

Study Record Dates

• First Submitted: November 21, 2013
• First Posted: November 27, 2013
• Study Start: November 1, 2013
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: November 13, 2014

Record last verified: 2014-11

Locations

IT (1)