Clinical trial NCT06884228: Effects of Vibrating Mesh Nebulisation in Patients With COPD During Non-invasive Ventilation (VMN-NIV)
Official title: Effects of Vibrating Mesh Nebulisation in Patients With COPD During Non-invasive Ventilation (VMN-NIV)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: COPD (Chronic Obstructive Pulmonary Disease)
Non-invasive Ventilation
Keywords: vibrating mesh nebuliser
jet nebuliser
Lead sponsor: Guy's and St Thomas' NHS Foundation Trust
Sponsor class: OTHER
First posted: 2025-03-19
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Pilot randomised crossover trial
Primary purpose: TREATMENT

Brief summary: Assessment of the effects of vibrating mesh nebulisation versus jet nebulisation on the electrical activity of the muscles involved in breathing (neural respiratory drive), breathing mechanics (respiratory impedance measured by forced oscillation technique), respiratory flow, heart rate and rhythm, spirometry and breathlessness symptoms in patients with chronic obstructive pulmonary disease who require non-invasive ventilation.

Detailed description: Background Chronic obstructive pulmonary disease (COPD) remains a leading cause of morbidity and mortality in the United Kingdom. Acute exacerbations of COPD (AECOPD) frequently necessitate hospitalisation, with standard treatment comprising nebulised bronchodilators, antibiotics, and systemic corticosteroids. Approximately 20% of patients hospitalised with AECOPD require non-invasive ventilation (NIV) to manage decompensated hypercapnic respiratory failure, often necessitating concurrent administration of nebulised therapy.

Home NIV use is increasing among COPD patients to improve respiratory symptoms, quality of life, reduce hospitalisation frequency, and enhance survival. These patients may also require nebulised bronchodilator therapy during NIV, particularly when managing acute exacerbations not severe enough to warrant hospitalisation.

Currently, two nebulisation modalities are used as standard of care for patients on NIV:

Jet nebulisation (JN) - the conventional delivery method Vibrating mesh nebulisation (VMN) - a newer technology that utilises a mesh membrane oscillating at high frequency to produce drug-carrying droplets of predetermined size

VMN has been developed to optimise drug delivery in various patient populations, including those who are spontaneously breathing, receiving invasive mechanical ventilation, or on NIV. This technology is designed to enhance pulmonary drug deposition while minimising residual drug volume post-nebulisation.

Previous research has demonstrated that VMN achieves superior pulmonary drug deposition during NIV compared to JN in both healthy subjects and stable COPD patients. VMN has also been shown to produce greater improvements in forced expiratory volume in one second (FEV₁) among hospitalised patients. However, the comparative effects of these nebulisation methods on physiological parameters such as neural respiratory drive and respiratory system impedance during NIV in COPD patients with chronic respiratory failure remain unexplored.

Study Objective This pilot randomised crossover trial aims to compare the physiological effects of vibrating mesh versus jet nebulisation of salbutamol during NIV in patients with chronic respiratory failure due to COPD.

Methods Study Design A randomised crossover trial with participants receiving both interventions with a 48-hour washout period between treatments.

Participants We will recruit 12 patients with COPD currently receiving NIV under the care of the Lane Fox Unit. All participants will provide written informed consent prior to study procedures.

Procedures

Following consent, we will record baseline data including:

NIV settings Anthropometric measurements Arterial blood gas analysis Clinical observations

Participants will be randomised to receive salbutamol via either VMN or JN during NIV. We will measure the following parameters at multiple time points within one hour after nebulisation:

Neural respiratory drive via parasternal electromyography Spirometry Respiratory impedance (mechanics of breathing)

Participants will self-report breathlessness using both a numerical scale and a validated scale.

After a minimum of 48-hour washout period, participants will return to repeat the protocol with the alternative nebuliser type.

Eligibility criteria: Inclusion Criteria:

* Patients with COPD receiving home non-invasive ventilation for chronic respiratory failure under the Lane Fox Respiratory Service at Guy's and St Thomas' NHS Foundation Trust
* Tolerating home non-invasive ventilation for at least 4 hours/24 hours
* Aged 18-80 years old
* Able to communicate symptom burden to the research team
* Able to give informed consent for participation in the study
* Clinical stability, with no acute exacerbations of COPD for 2 weeks prior to enrolment

Exclusion Criteria:

* Severe, non-respiratory organ dysfunction including, but not limited to:

  * Congestive cardiac failure
  * Significant cardiovascular disease
  * End-stage malignancy
  * End-stage renal failure
* Acute pulmonary pathology requiring emergency treatment including, but not limited to:

  * Pneumonia
  * Pneumothorax
  * Pulmonary embolism
* Severe cognitive impairment
* Psychosocial factors that would preclude completion of the study protocol

Primary outcomes:
measure: Change in neural respiratory drive
timeFrame: NRD assessed on both visits at baseline and 5, 15, 30 and 60 minutes after nebulisation
Secondary outcomes:
measure: Respiratory System impedence
timeFrame: Both visits at baseline, 5 and 60 minutes post nebulisation therapy.
measure: Symptom of Breathlessness (numerical rating scale)
timeFrame: At baseline and at 5, 15, 30 and 60 minutes post nebulisation on both visits
measure: Symptom of Breathlessness (modified Borg Dyspnoea scale)
timeFrame: At baseline and at 5, 15, 30 and 60 minutes post nebulisation on both visits
measure: Transcutaneous CO2 Monitoring
timeFrame: At baseline and for 60 minutes following nebulisation
measure: Spirometry - Forced expiratory volume in 1 second
timeFrame: At baseline and during 1 hour after administration of nebuliser on both visits
measure: Spirometry - Forced vital capacity
timeFrame: At baseline and during 1 hour after administration of nebuliser on both visits
measure: Spirometry ratio - FEV1/FVC
timeFrame: At baseline and during 1 hour after administration of nebuliser on both visits
measure: Cardiac rate
timeFrame: At baseline and for 60 minutes following nebulisation
measure: Cardiac rhythm
timeFrame: At baseline and for 60 minutes following nebulisation
measure: Respiratory flow
timeFrame: At baseline and for 60 minutes following nebulisation
Other outcomes:
measure: Arterial blood gas
timeFrame: At baseline on first visit
Locations:
city: London
country: United Kingdom
facility: Lane Fox Unit, St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust
Study officials:
affiliation: Guy's and St Thomas' NHS Foundation Trust
name: Eui-Sik Suh, MBBS MChem(Oxon) PhD FRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Davidson AC, Banham S, Elliott M, Kennedy D, Gelder C, Glossop A, Church AC, Creagh-Brown B, Dodd JW, Felton T, Foex B, Mansfield L, McDonnell L, Parker R, Patterson CM, Sovani M, Thomas L; BTS Standards of Care Committee Member, British Thoracic Society/Intensive Care Society Acute Hypercapnic Respiratory Failure Guideline Development Group, On behalf of the British Thoracic Society Standards of Care Committee. BTS/ICS guideline for the ventilatory management of acute hypercapnic respiratory failure in adults. Thorax. 2016 Apr;71 Suppl 2:ii1-35. doi: 10.1136/thoraxjnl-2015-208209. No abstract available.
citation: Plant PK, Owen JL, Elliott MW. Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial. Lancet. 2000 Jun 3;355(9219):1931-5. doi: 10.1016/s0140-6736(00)02323-0.
citation: Brochard L. Non-invasive ventilation for acute exacerbations of COPD: a new standard of care. Thorax. 2000 Oct;55(10):817-8. doi: 10.1136/thorax.55.10.817. No abstract available.