Clinical trial NCT02576626: Single Dose Ultibro Breezhaler by Sd-DPI Versus Ipratropium/Salbutamol by Nebulizer in COPD
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: COPD
Keywords: Nebulizer
DPI
COPD
indacaterol
ipratropium
glycopyrronium
salbutamol
Breezhaler
Nebuliser
Hyperinflation
Dyspnea
SABA
short-acting muscarinic antagonists (SAMA)
long-acting beta2-agonist (LABA)
LAMA
FEV1
Lead sponsor: Groningen Research Institute for Asthma and COPD
Sponsor class: OTHER
Collaborators: name: Novartis
name: University Medical Center Groningen
First posted: 2015-10-15
Enrollment: 40
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Area under the curve (AUC) of FEV1
timeFrame: from 0 to 6 hours
Secondary outcomes:
measure: Change in Borg dyspnea score at 30 min
timeFrame: 30 min up to 360 minutes
measure: Proportion of patients reaching the minimal clinically important difference (MCID) at all time points
timeFrame: all time points (15, 30, 60, 120 240 and 360 min)
measure: Changes in level of hyperinflation (by IC measurement)
timeFrame: all time points (15, 30, 60, 120 240 and 360 min)
measure: Time to FEV1 increase of 100 ml
timeFrame: all time points (15, 30, 60, 120 240 and 360 min)
measure: Peak effect of FEV1
timeFrame: from 0 to 6 hours
measure: Time to peak of FEV1
timeFrame: all time points (15, 30, 60, 120 240 and 360 min)
measure: FEV1
timeFrame: at all time points (15, 30, 60, 120 240 and 360 min)
measure: Proportion of participants reaching a difference of 100 ml of inspiratory capacity (IC)
timeFrame: Time Frame: all time points (15, 30, 60, 120 240 and 360 min)
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: UMCG
Study officials:
affiliation: Groningen Research Institute for Asthma and COPD
name: Huib AM Kerstjens, prof. dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Frisius Medisch Centrum
name: Wouter H van Geffen, MD
role: STUDY_DIRECTOR
References: