Effectiveness of Bronchodilator Nebulization With and Without Noninvasive Ventilation in COPD

Effectiveness of Bronchodilator Nebulization With and Without Noninvasive Ventilation During Respiratory Failure in Chronic Obstructive Pulmonary Disease

The study aim to evaluate effectiveness of two bronchodilator nebulization strategies in patients with acute decompensated type 2 respiratory failure due to acute exacerbation of chronic obstructive pulmonary disease..

Study Overview

• Status: Terminated
• Conditions: Chronic Obstructive Pulmonary Disease (COPD); Type 2 Respiratory Failure
• Intervention / Treatment: Procedure: In-line nebulization through NIV mask; Procedure: Off-NIV nebulization

Detailed Description

Decompensated type 2 respiratory failure during acute exacerbation of chronic obstructive pulmonary disease (COPD) is treated with non-invasive ventilation (NIV) and nebulized bronchodilators. Nebulization during NIV can be applied by two methods: in-line nebulization through NIV mask and off-NIV nebulization during which NIV mask is taken off for a short time and reapplied when nebulization is finished.

This study is a prospective randomized controlled trial to compare in-line nebulization through NIV versus off- NIV nebulization. After starting NIV in eligible COPD patients with type 2 respiratory failure, the baseline end-expiratory lung impedance (EELI) will be measured. Patient is randomized to receive either in-line or off-NIV nebulization. EELI will be measured again following completion of the nebulization, 15min after NIV is restarted (off-NIV group) or continued (in-line group). Ultrasound measurement of the thickness of the diaphragm will be recorded at baseline, 15min after NIV is restarted (off-NIV group) or continued (in-line group) and 48 hours after stopping the NIV. The main outcome measure, difference in mean end expiratory lung volume at 15min after NIV is restarted (off-NIV group) or continued (in-line group) between the two nebulization methods will be compared using independent sample T test. Thickness of the diaphragm and changes in the arterial blood gases (in terms of pH and carbon-di-oxide) will be compared between in-line nebulization and off-NIV nebulization.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore
    • National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥21 years.
2. Known or suspected COPD (defined by a ratio of Forced Expiratory Volume in 1 second (FEV1) to Forced Vital Capacity (FVC) of less than 0.7).
3. Acute decompensated type 2 respiratory failure (ABG pH ≤ 7.35 and PaCO2>45mmHg).
4. Clinical decision made to start NIV.

Exclusion Criteria:

1. Other acute decompensated type 2 respiratory failure related conditions (e.g. neuromuscular, heart failure etc.).
2. Pneumonia present in the chest radiograph.
3. Other conditions which may change lung impedance (e.g. heart failure or lung fibrosis).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: In-line nebulization through NIV mask; Bronchodilator nebulization is given through NIV circuit.	Procedure: In-line nebulization through NIV mask; In-line nebulization will be given through NIV circuit.
Active Comparator: Off-NIV nebulization; Bronchodilator nebulization is given during which NIV mask is taken off for a short time and reapplied when nebulization is finished.	Procedure: Off-NIV nebulization; Bronchodilator nebulization is given during which NIV mask is taken off for a short time and reapplied when nebulization is finished..

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in mean end-expiratory lung volumes between the two nebulization methods.	End-expiratory lung volumes between in-line nebulization and off-NIV nebulization.	At baseline (approximately 15min after starting NIV) to approximately 15min after restarting (or continuing NIV) following the nebulization.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thickness of the diaphragm (by ultrasound) between in-line nebulization and off-NIV nebulization.	Measure thickness of the diaphragm between inspiration and expiration.	At baseline (approximately 15min after starting NIV) to approximately 15min after restarting (or continuing NIV) following the nebulization and repeated 48hours after stopping NIV.
Changes in arterial blood gases in terms of pH and carbon dioxide between in-line. nebulization and off-NIV nebulization.	Measure changes of arterial blood gases between in-line nebulization and off-NIV. nebulization. Differences in pH (absolute,no unit) and carbon dioxide (in mmHg) will be noted.	At baseline (approximately 15min after starting NIV) to approximately 15min after restarting (or continuing NIV) following the nebulization.

Collaborators and Investigators

• Sponsor: National University Health System, Singapore
• Investigators: Principal Investigator: Amartya Mukhopadhyay, MBBS, National University Health System

Publications and helpful links

General Publications

• Vivier E, Mekontso Dessap A, Dimassi S, Vargas F, Lyazidi A, Thille AW, Brochard L. Diaphragm ultrasonography to estimate the work of breathing during non-invasive ventilation. Intensive Care Med. 2012 May;38(5):796-803. doi: 10.1007/s00134-012-2547-7. Epub 2012 Apr 5.
• Brochard L, Mancebo J, Wysocki M, Lofaso F, Conti G, Rauss A, Simonneau G, Benito S, Gasparetto A, Lemaire F, et al. Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med. 1995 Sep 28;333(13):817-22. doi: 10.1056/NEJM199509283331301.
• Pauwels RA, Buist AS, Calverley PM, Jenkins CR, Hurd SS; GOLD Scientific Committee. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Am J Respir Crit Care Med. 2001 Apr;163(5):1256-76. doi: 10.1164/ajrccm.163.5.2101039. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2018
• Primary Completion (Actual): November 12, 2020
• Study Completion (Actual): November 12, 2020

Study Registration Dates

• First Submitted: March 15, 2018
• First Submitted That Met QC Criteria: March 27, 2018
• First Posted (Actual): March 29, 2018

Study Record Updates

• Last Update Posted (Actual): October 13, 2022
• Last Update Submitted That Met QC Criteria: October 10, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Nebulization; Respiratory failure; Chronic Obstructive Pulmonary Disease (COPD); Non-invasive ventilation(NIV)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Insufficiency
• Other Study ID Numbers: DSRB 2017/00990

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No