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

NCT02576626 | Completed Phase 4 DMC

• 1 other identifier: NL5250604215
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Change in Borg dyspnea score at 30 min

  30 min up to 360 minutes

• 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)

• Changes in level of hyperinflation (by IC measurement)

  all time points (15, 30, 60, 120 240 and 360 min)

• Time to FEV1 increase of 100 ml

  all time points (15, 30, 60, 120 240 and 360 min)

• Peak effect of FEV1

  from 0 to 6 hours

Study Arms (2)

A

OTHER

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®; Device: Placebo by Breezhaler®; Drug: ipratropium/salbutamol 0,5 mg, 2,5 mg by nebulisation; Device: Placebo by nebulisation

B

OTHER

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®; Device: Placebo by Breezhaler®; Drug: ipratropium/salbutamol 0,5 mg, 2,5 mg by nebulisation; Device: Placebo by nebulisation

Interventions

indacaterol/glycopyrronium 110/50 Breezhaler® DRUG

Also known as: Ultibro

A; B

Placebo by Breezhaler® DEVICE

A; B

ipratropium/salbutamol 0,5 mg, 2,5 mg by nebulisation DRUG

Also known as: Combivent

A; B

Placebo by nebulisation DEVICE

A; B

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Allergic reaction or intolerance for a substance used in one of the products or atropine or atropine derived substances
• Pregnant or lactating females.

Sponsors & Collaborators

• Wouter H. van Geffen: lead
• Novartis: collaborator
• University Medical Center Groningen: collaborator

Study Sites (1)

UMCG

Groningen, 9700RB, Netherlands

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Dyspnea

Interventions

indacaterol; Ipratropium; Albuterol, Ipratropium Drug Combination

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Atropine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Belladonna Alkaloids; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Amines; Phenethylamines; Ethylamines; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Huib AM Kerstjens, prof. dr.

  Groningen Research Institute for Asthma and COPD

  PRINCIPAL INVESTIGATOR

• Wouter H van Geffen, MD

  Frisius Medisch Centrum

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Arts onderzoeker

Study Record Dates

• First Submitted: August 4, 2015
• First Posted: October 15, 2015
• Study Start: December 1, 2015
• Primary Completion: September 29, 2017
• Study Completion: September 29, 2017
• Last Updated: October 11, 2017

Record last verified: 2017-10

Locations

NL (1)