Single Dose Ultibro Breezhaler by Sd-DPI Versus Ipratropium/Salbutamol by Nebulizer in COPD
Single Dose Ultibro Breezhaler by Sd-DPI Versus Ipratropium/Salbutamol by Nebulizer in COPD
Rationale:

 Inhaled bronchodilators, beta-2-agonist or anticholinergic or combinations, can be delivered
 by several types of devices: dry powder (DPI), pressurized metered dose inhalers (pMDI), and
 wet nebulizers. Wet nebulization is available for short-acting bronchodilators only, is
 cumbersome, and, importantly, has never been scientifically been proven to be more
 efficacious than delivery by the other two methods. Yet many patients are happy with wet
 nebulization and in many clinics this administration method prevails. The investigators
 believe that combined long-acting bronchodilators, are more efficacious than combined short
 acting bronchodilators per nebulizers.

 Objective:

 To test the hypothesis that: The combination of the two long-acting bronchodilators
 indacaterol and glycopyrronium by dry powder inhalation confers a superior improvement
 compared to nebulisation with ipratropium/salbutamol, when administered as single dose in
 patients with stable state chronic obstructive pulmonary disease (COPD).

 Study design: Investigator initiated, randomised, active controlled, cross-over double-blind
 (and therefore double-dummy), study comparing the effects of single dose
 indacaterol/glycopyrronium 110/50 Breezhaler® versus single dose ipratropium/salbutamol
 nebulisation in patients with COPD in stable state Study population: Patients visiting the
 outpatient clinics or from general practitioner (GP) practices with COPD GOLD stage A-D, and
 (FEV1) post-bronchodilator FEV1/ forced vital capacity (FVC) < 70%; post-br FEV1 < 80%pred.
 Intervention The investigators will compare the effects of single dose
 indacaterol/glycopyrronium 110/50 Breezhaler® versus single dose ipratropium/salbutamol
 nebulisation in patients with COPD in stable state

 Main study parameters/endpoints:

 Area under the curve (AUC) from 0 to 6 hours of FEV1 with indacaterol and glycopyrronium,
 compared to nebulisation with ipratropium/salbutamol

 Nature and extent of the burden and risks associated with participation, benefit and group
 relatedness:

 This study has no specific benefits for the participating patients. The study also has no
 major risks. Minor risks for participants after a single dosis can be throat irritation,
 cough, headache and dizziness, sinus tachycardia. The combination of treatments with
 β2-agonist bronchodilators and anticholinergic bronchodilators have been used in daily
 practice for many years in many countries and they are often prescribed both in COPD. Both
 indacaterol/glycopyrronium and ipratropium/salbutamol are approved for COPD treatment in the
 Netherlands
Inclusion Criteria:

 1. COPD, post-bronchodilator FEV1/FVC < 70%; post-br FEV1 < 80%pred

 2. Active mastery of Dutch

 3. Written informed consent

 4. At least 40 years old

 5. Participants must be able to understand and complete protocol requirements,
 Instructions, and questionnaires provided in Dutch

 Exclusion Criteria:

 1. Non invasive ventilation

 2. Saturation by pulse oxymetry <88%

 3. Documented history of asthma

 4. Instable cardiac disease within 6 months.

 5. Known long corrected QT interval (QTC) syndrome

 6. Known estimated Glomerular Filtration Rate (EGFR) ( <30 ml/min *1,73m2

 7. Exacerbations of COPD or change of medication for COPD in the last 6 weeks prior to
 inclusion

 8. Allergic reaction or intolerance for a substance used in one of the products or
 atropine or atropine derived substances

 9. Pregnant or lactating females.