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

October 10, 2017 updated by: Wouter H. van Geffen

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: A
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
Drug: indacaterol/glycopyrronium 110/50 Breezhaler®
Other Names:
  • Ultibro
Device: Placebo by Breezhaler®
Drug: ipratropium/salbutamol 0,5 mg, 2,5 mg by nebulisation
Other Names:
  • Combivent
Device: Placebo by nebulisation
Other: B

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
Drug: indacaterol/glycopyrronium 110/50 Breezhaler®
Other Names:
  • Ultibro
Device: Placebo by Breezhaler®
Drug: ipratropium/salbutamol 0,5 mg, 2,5 mg by nebulisation
Other Names:
  • Combivent
Device: Placebo by nebulisation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area under the curve (AUC) of FEV1
Time Frame: 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.
from 0 to 6 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Borg dyspnea score at 30 min
Time Frame: 30 min up to 360 minutes
1. Change in Borg dyspnea score at 30 min: change in Borg score at other time points
30 min up to 360 minutes
Proportion of patients reaching the minimal clinically important difference (MCID) at all time points
Time Frame: 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)
all time points (15, 30, 60, 120 240 and 360 min)
Changes in level of hyperinflation (by IC measurement)
Time Frame: all time points (15, 30, 60, 120 240 and 360 min)
all time points (15, 30, 60, 120 240 and 360 min)
Time to FEV1 increase of 100 ml
Time Frame: all time points (15, 30, 60, 120 240 and 360 min)
all time points (15, 30, 60, 120 240 and 360 min)
Peak effect of FEV1
Time Frame: from 0 to 6 hours
Maximum FEV1 per group, calculated using the best FEV1 per participant
from 0 to 6 hours
Time to peak of FEV1
Time Frame: all time points (15, 30, 60, 120 240 and 360 min)
all time points (15, 30, 60, 120 240 and 360 min)
FEV1
Time Frame: at all time points (15, 30, 60, 120 240 and 360 min)
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: Time Frame: all time points (15, 30, 60, 120 240 and 360 min)
Time Frame: all time points (15, 30, 60, 120 240 and 360 min)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wouter H. van Geffen

Collaborators

Novartis
University Medical Center Groningen

Investigators

  • Principal Investigator: Huib AM Kerstjens, prof. dr., Groningen Research Institute for Asthma and COPD
  • Study Director: Wouter H van Geffen, MD, Medical Centre Leeuwarden

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2015

Primary Completion (Actual)

September 29, 2017

Study Completion (Actual)

September 29, 2017

Study Registration Dates

First Submitted

August 4, 2015

First Submitted That Met QC Criteria

October 14, 2015

First Posted (Estimate)

October 15, 2015

Study Record Updates

Last Update Posted (Actual)

October 11, 2017

Last Update Submitted That Met QC Criteria

October 10, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL5250604215

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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