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

COPD Clinical Trial

— ULT01  

Official title:

The Effectiveness of Single Dose Ultibro Breezhaler (Indacaterol/Glycopyrronium) by Sd-DPI Versus Ipratropium/Salbutamol by Nebulizer in Improving FEV1 and Dyspnea During Stable State of COPD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02576626
• Other study ID #: NL5250604215
• Status: Completed
• Phase: Phase 4
• First received: August 4, 2015
• Last updated: October 10, 2017
• Start date: December 2015
• Est. completion date: September 29, 2017

Study information

• Verified date: October 2017
• Source: Groningen Research Institute for Asthma and COPD
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: September 29, 2017
• Est. primary completion date: September 29, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COPD

Intervention

Drug:
• indacaterol/glycopyrronium 110/50 Breezhaler®

Device:
• Placebo by Breezhaler®

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

Device:
• Placebo by nebulisation

Locations

Country	Name	City	State
Netherlands	UMCG	Groningen

Sponsors (3)

Lead Sponsor	Collaborator
Wouter H. van Geffen	Novartis, University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the curve (AUC) of FEV1	Area under the curve (AUC) from 0 to 6 hours of FEV1 with indacaterol and glycopyrronium, compared to nebulisation with ipratropium/salbutamol.	from 0 to 6 hours
Secondary	Change in Borg dyspnea score at 30 min	1. Change in Borg dyspnea score at 30 min: change in Borg score at other time points	30 min up to 360 minutes
Secondary	Proportion of patients reaching the minimal clinically important difference (MCID) at all time points	proportion of patients reaching the MCID at all time points (15, 30, 60, 120 240 and 360 min) (1)	all time points (15, 30, 60, 120 240 and 360 min)
Secondary	Changes in level of hyperinflation (by IC measurement)		all time points (15, 30, 60, 120 240 and 360 min)
Secondary	Time to FEV1 increase of 100 ml		all time points (15, 30, 60, 120 240 and 360 min)
Secondary	Peak effect of FEV1	Maximum FEV1 per group, calculated using the best FEV1 per participant	from 0 to 6 hours
Secondary	Time to peak of FEV1		all time points (15, 30, 60, 120 240 and 360 min)
Secondary	FEV1		at all time points (15, 30, 60, 120 240 and 360 min)
Secondary	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)