Efficacy of an Advanced Auto-titrating NIV in COPD

Study Overview
=================
Brief Summary
-----------------
Patients with chronic obstructive pulmonary disease (COPD) can eventually progress to respiratory failure, where they cannot adequately exchange oxygen and carbon dioxide, leading to worsening breathlessness, frequent hospitalisations and death. Non-invasive ventilation (NIV) is a ventilator therapy that is used in COPD patients who suffer from respiratory failure. Studies have demonstrated that using NIV at night regularly can result in improved clinical outcomes. Adherence to this therapy is variable, however. This can be due to poor synchrony between the device and the lungs. A novel ventilator has been designed that delivers NIV but is also incorporated with technology to assess for aberrations in respiratory physiology and correct them, breath-by-breath. The investigators aim to assess the efficacy, safety and tolerability of this novel ventilator. The primary research question is whether the novel ventilator can improve adherence to therapy, when compared with the usual ventilator. Patients with COPD who use ventilation at home will be screened for inclusion in the study. Participation will involve a screening visit, and a further two visits to the Lane Fox Respiratory Unit. The first will require a two-night admission and the second a single-night admission. They will undergo detailed assessment of their daytime and overnight respiratory and sleep physiology during these admissions. These visits will be separated by a six-week period during which they will be asked to use the novel ventilator at home. Patients will be recruited into a sub-study to evaluate the performance of the ventilator in a daytime physiological assessment. This will involve detailed invasive physiological assessment of expiratory flow limitation and how the machine is able to adjust settings to optimise respiratory support.

Official Title
-----------------
Clinical Validation, Safety & Efficacy Study of an Advanced Auto-titrating Non-invasive Ventilator in Patients With Severe Chronic Obstructive Pulmonary Disease

Conditions
-----------------
Chronic Obstructive Pulmonary Disease Severe

Intervention / Treatment
-----------------
* Device: Auto-titrating non-invasive ventilation


Participation Criteria
=================
Eligibility Criteria
-----------------
Patient Inclusion Criteria: Age ≥ 18 years BMI <30 kg/m¬2 Confirmed diagnosis of COPD Currently using domiciliary NIV with average reported compliance of at least 3hours Ability to provide informed consent Medical stability confirmed by recruiting physician Free of exacerbations for at least 2 weeks prior to enrolment Presence of expiratory flow limitation on forced oscillation technique criteria Exclusion Criteria: Current acute illness as determined by recruiting physician e.g. upper respiratory tract infection Presence of major medical comorbidity, e.g. severe heart failure (LVEF <30%), active malignancy, end-stage renal failure (CKD 4), and neuromuscular disease Subjects who have had surgery of the upper airway, nose, sinus, or middle ear within the previous 90 days. Psychosocial factors that would prevent compliance with study protocol Healthy participant inclusion criteria: Age ≥ 18 years No expiratory flow limitation on forced oscillation testing No acute illness on study day Ability to provide informed consent

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: 12 weeks sequential (pre/post) study. Participants will receive usual NIV treatment for 6 weeks followed by novel ventilator for 6 weeks. There will be a randomised crossover element for one night at the midpoint of the study to assess sleep parameters on the two ventilation modalities.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Usual non-invasive ventilation<br>The usual therapy the participant is receiving via non-invasive ventilator. | |
| Experimental: Auto-titrating non-invasive ventilation<br>A novel auto-titrating non-invasive ventilator | Device: Auto-titrating non-invasive ventilation<br>* A non-invasive ventilator designed to auto-adjust the expiratory positive airway pressure according to expiratory flow limitation, measured using the forced oscillation technique.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adherence to ventilation therapy | Number of hours spent on nocturnal ventilation therapy | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean nocturnal transcutaneous carbon dioxide level | Mean nocturnal transcutaneous carbon dioxide level measured on single night admission | 1 night during single night admission | 
| Maximal nocturnal transcutaneous carbon dioxide level | Maximal nocturnal transcutaneous carbon dioxide level measured on single night admission | 1 night during single night admission | 
| Sleep parameters | Sleep efficiency, measured by polysomnography | 1 night during single night admission | 
| Sleep parameters | Wake after sleep onset, measured by polysomnography | 1 night during single night admission | 
| Sleep parameters | Time in rapid eye movement/non rapid eye movement sleep, measured by polysomnography | 1 night during single night admission | 
| Sleep parameters | Apnoea/hypopnoea index, measured by polysomnography | 1 night during single night admission | 
| Sleep parameters | 4 per cent oxygen desaturation index, measured by polysomnography | 1 night during single night admission | 
| Inspiratory capacity | Inspiratory capacity following 6 weeks of each NIV device | 6 weeks | 
| Health-related quality of life | Measured using COPD Assessment Test | 6 weeks | 
| Health-related quality of life | Measured using Severe Respiratory Insufficiency Questionnaire | 6 weeks | 
| Daytime physical activity | Measured using wrist actigraphs during the final 2 weeks of each 6 week arm | 2 weeks |