Single Dose Ultibro Breezhaler by Sd-DPI Versus Ipratropium/Salbutamol by Nebulizer in COPD
- Conditions
- COPD
- Interventions
- Drug: indacaterol/glycopyrronium 110/50 Breezhaler®Device: Placebo by Breezhaler®Drug: ipratropium/salbutamol 0,5 mg, 2,5 mg by nebulisationDevice: Placebo by nebulisation
- Registration Number
- NCT02576626
- Lead Sponsor
- Wouter H. van Geffen
- Brief Summary
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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
- COPD, post-bronchodilator FEV1/FVC < 70%; post-br FEV1 < 80%pred
- Active mastery of Dutch
- Written informed consent
- At least 40 years old
- Participants must be able to understand and complete protocol requirements, Instructions, and questionnaires provided in Dutch
- Non invasive ventilation
- Saturation by pulse oxymetry <88%
- Documented history of asthma
- Instable cardiac disease within 6 months.
- Known long corrected QT interval (QTC) syndrome
- Known estimated Glomerular Filtration Rate (EGFR) ( <30 ml/min *1,73m2
- Exacerbations of COPD or change of medication for COPD in the last 6 weeks prior to inclusion
- Allergic reaction or intolerance for a substance used in one of the products or atropine or atropine derived substances
- Pregnant or lactating females.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description A indacaterol/glycopyrronium 110/50 Breezhaler® 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 A ipratropium/salbutamol 0,5 mg, 2,5 mg by nebulisation 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 B indacaterol/glycopyrronium 110/50 Breezhaler® 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 A Placebo by Breezhaler® 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 A Placebo by nebulisation 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 B ipratropium/salbutamol 0,5 mg, 2,5 mg by nebulisation 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 B Placebo by Breezhaler® 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 B Placebo by nebulisation 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
- Primary Outcome Measures
Name Time Method Area under the curve (AUC) of FEV1 from 0 to 6 hours Area under the curve (AUC) from 0 to 6 hours of FEV1 with indacaterol and glycopyrronium, compared to nebulisation with ipratropium/salbutamol.
- Secondary Outcome Measures
Name Time Method Time to FEV1 increase of 100 ml all time points (15, 30, 60, 120 240 and 360 min) Changes in level of hyperinflation (by IC measurement) all time points (15, 30, 60, 120 240 and 360 min) Time to peak of FEV1 all time points (15, 30, 60, 120 240 and 360 min) Change in Borg dyspnea score at 30 min 30 min up to 360 minutes 1. Change in Borg dyspnea score at 30 min: change in Borg score at other time points
Proportion of patients reaching the minimal clinically important difference (MCID) at all time points all time points (15, 30, 60, 120 240 and 360 min) proportion of patients reaching the MCID at all time points (15, 30, 60, 120 240 and 360 min) (1)
Peak effect of FEV1 from 0 to 6 hours Maximum FEV1 per group, calculated using the best FEV1 per participant
FEV1 at all time points (15, 30, 60, 120 240 and 360 min) Proportion of participants reaching a difference of 100 ml of inspiratory capacity (IC) Time Frame: all time points (15, 30, 60, 120 240 and 360 min)
Trial Locations
- Locations (1)
UMCG
🇳🇱Groningen, Netherlands