Single Dose Ultibro Breezhaler by Sd-DPI Versus Ipratropium/Salbutamol by Nebulizer in COPD (ULT01)

Wouter H. van Geffen

Status and phase: Completed; Phase 4

Conditions: COPD

Treatments: Drug: indacaterol/glycopyrronium 110/50 Breezhaler®; Device: Placebo by nebulisation; Device: Placebo by Breezhaler®; Drug: ipratropium/salbutamol 0,5 mg, 2,5 mg by nebulisation

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02576626

NL5250604215

Details and patient eligibility

About

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

Enrollment: 40 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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40 participants in 2 patient groups

A

Other group

Description:

Participants start with Ultibro (indacaterol/glycopyrronium 110/50) + placebo nebulization , then after a new washout period of 7 days they will receive ipratropium/salbutamol nebulization and placebo Breezhaler Interventions: indacaterol/glycopyrronium 110/50 Breezhaler® ,Placebo by Breezhaler®, ipratropium/salbutamol 0,5 mg, 2,5 mg by nebulisation, Placebo by nebulisation

Treatment:

Device: Placebo by nebulisation

Device: Placebo by Breezhaler®

Drug: ipratropium/salbutamol 0,5 mg, 2,5 mg by nebulisation

Drug: indacaterol/glycopyrronium 110/50 Breezhaler®

B

Other group

Description:

Participants start with ipratropium/salbutamol nebulization and placebo Breezhaler , then after a new washout period of 7 days they will receive Ultibro(indacaterol/glycopyrronium 110/50) + placebo nebulization. Interventions: indacaterol/glycopyrronium 110/50 Breezhaler® ,Placebo by Breezhaler®, ipratropium/salbutamol 0,5 mg, 2,5 mg by nebulisation, Placebo by nebulisation

Treatment:

Device: Placebo by nebulisation

Device: Placebo by Breezhaler®

Drug: ipratropium/salbutamol 0,5 mg, 2,5 mg by nebulisation

Drug: indacaterol/glycopyrronium 110/50 Breezhaler®