Chest Wall Disorder, Neuromuscular Disease, Nocturnal Hypoventilation
Conditions
Keywords
Respiratory insufficiency, Hypercapnia, Hypoventilation, Sleep, Polysomnography, Hypoxia, Titration, Non Invasive Ventilation
Brief summary
The aim of the study is to compare the efficacy and tolerance of autotitrating non-invasive ventilation (NIV) versus standard NIV in patients with newly diagnosed nocturnal hypoventilation who have never experienced nocturnal, home NIV.
Detailed description
The aim of the study is to compare the effect of two types of noninvasive ventilator (a small machine that assists breathing) in patients newly diagnosed with nocturnal hypoventilation who are inexperienced in the use of noninvasive ventilation (NIV). NIV is standard therapy for patients with nocturnal hypoventilation. The most common type of NIV is bilevel pressure support which assists patient breathing by delivering different levels of air pressure during inspiration and expiration via a mask covering the nose or nose and mouth. Standard bilevel NIV (VPAP™) has been further developed to create a new automatically adjusting NIV (AutoVPAP™). Automatically adjusting NIV varies the inspiratory air pressure according to the airflow rates generated by the patient. This may improve patient comfort, hours of NIV use and recovery time. Patients over the age of 18 referred to, or under follow up at, the Royal Brompton Hospital who require domiciliary NIV but are inexperienced with use of NIV will be considered for entry into this randomised crossover study. If eligible for inclusion and willing to take part patients will be setup on automatically adjusting NIV or standard NIV, assigned in random order. At the end of one month the patient will be swapped to the alternative NIV for a further one month of domiciliary NIV treatment. At the end of each one month treatment period the patient will undergo overnight polysomnography, transcutaneous CO2 monitoring and 24 hour Holter monitoring.
Interventions
DEVICEAutoVPAP
Automatically titrated non-invasive ventilator, with target gross alveolar ventilation and back up respiratory rate determined by learn function. Nocturnal use for one month in patient's home.
DEVICEVPAPIIIST-A
Standard non-invasive ventilator with pressure and respiratory rate settings determined by healthcare professional. Nocturnal use for one month in the patient's home.
Sponsors
Royal Brompton & Harefield NHS Foundation Trust
ResMed
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* new clinical diagnosis of nocturnal hypoventilation * requirement for long-term domiciliary non-invasive ventilation * no previous experience with domiciliary non-invasive ventilation
Exclusion criteria
* uncontrolled cardiac failure * acute exacerbation of respiratory failure * daytime resting PaO2 \< 7.5kPa * moderate or severe bulbar weakness * inability to understand rationale and/or consent form for study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overnight Mean Oxygen Saturation | 4 weeks | Overnight oximetry (SaO2) and transcutaneous capnography (PtcCO2) (TOSCA, Linde Medical Sensors, Switzerland) were performed during a sleep a on NIV at the end of each month's NIV therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overnight Mean Transcutaneous Carbon Dioxide | 4 weeks | Overnight oximetry (SaO2) and transcutaneous capnography (PtcCO2) (TOSCA, Linde Medical Sensors, Switzerland) were performed during a sleep a on NIV at the end of each month's NIV therapy. |
| Overnight Peak Transcutaneous Carbon Dioxide | 4 weeks | Overnight oximetry (SaO2) and transcutaneous capnography (PtcCO2) (TOSCA, Linde Medical Sensors, Switzerland) were performed during a sleep a on NIV at the end of each month's NIV therapy. |
| Oxygen Desaturation Index (>4%) | 4 weeks | Overnight oximetry (SaO2) and transcutaneous capnography (PtcCO2) (TOSCA, Linde Medical Sensors, Switzerland) were performed during a sleep a on NIV at the end of each month's NIV therapy. ODI is the number of events per hour that SaO2 drops by \>4%. |
| Sleep Quality: Arousal Index | 4 weeks | A full PSG was performed during a sleep a on NIV at the end of each month's NIV therapy. Standard polysomnography analysis was performed by two team members blinded to patient identity and ventilator mode (REP/JJ). Sleep quality was assessed by the Arousal Index (no of arousals/hour) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Subjective Ventilator Tolerance: Comfort of Breath Delivered | 4 weeks | Subjective tolerance of ventilator modes was assessed by 10cm visual analogue scales (VAS) in response to questions on comfort of breath, ease of falling asleep, use of ventilator, and mode preference. VAS was scored from 0-100 for each question (0 - negative and 100 -s positive) |
| Subjective Ventilator Tolerance: Ease of Falling Asleep | 4 weeks | Subjective tolerance of ventilator modes was assessed by 10cm visual analogue scales (VAS) in response to questions on comfort of breath, ease of falling asleep, use of ventilator, and mode preference. VAS was scored from 0-100 for each question (0 - negative and 100 -s positive) |
| Ventilator Adherence | 4 weeks | Summary data from the ventilators were downloaded after each month's therapy, including adherence (hours of use), and ventilator output (nightly mean pressure support, minute ventilation (MV), RR and leak). |
| Subjective Ventilator Tolerance: Liked Using Ventilator | 4 weeks | Subjective tolerance of ventilator modes was assessed by 10cm visual analogue scales (VAS) in response to questions on comfort of breath, ease of falling asleep, use of ventilator, and mode preference. VAS was scored from 0-100 for each question (0 - negative and 100 -s positive) |
| Ventilator Mode Preference | 4 weeks | Subjective tolerance of ventilator modes was assessed by 10cm visual analogue scales (VAS) in response to questions on comfort of breath, ease of falling asleep, use of ventilator, and mode preference. VAS was scored from 0-100 for each question (0 - negative and 100 -s positive) |
| Subjective Ventilation Tolerance: Ease of Use of Ventilator | 4 weeks | Subjective tolerance of ventilator modes was assessed by 10cm visual analogue scales (VAS) in response to questions on comfort of breath, ease of falling asleep, use of ventilator, and mode preference. VAS was scored from 0-100 for each question (0 - negative and 100 -s positive) |
| Median Overnight Minute Ventilation | 4 weeks | Summary data from the ventilators were downloaded after each month's therapy, including adherence (hours of use), and ventilator output (nightly mean pressure support, minute ventilation (MV), RR and leak). |
| Median Overnight Pressure Support | 4 weeks | Summary data from the ventilators were downloaded after each month's therapy, including adherence (hours of use), and ventilator output (nightly mean pressure support, minute ventilation (MV), RR and leak). |
| Median Overnight Tidal Volume | 4 weeks | Summary data from the ventilators were downloaded after each month's therapy, including adherence (hours of use), and ventilator output (nightly mean pressure support, minute ventilation (MV), RR and leak). |
| Median Overnight Respiratory Rated | 4 weeks | Summary data from the ventilators were downloaded after each month's therapy, including adherence (hours of use), and ventilator output (nightly mean pressure support, minute ventilation (MV), RR and leak). |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Patients Patients underwent a cross over study design. In a randomised order they used 1 month of domiciliary nocturnal autotitrating, intelligent volume assured pressure support (iVAPS) non-invasive ventilation, and one month of standard non-invasive ventilation | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | All Patients |
|---|---|
| Age, Continuous | 54 years |
| FEV1 (forced expiratory volume) (L) | 1.5 L |
| FEV1/FVC | 0.75 ratio |
| FVC (forced vital capacity) | 1.9 L |
| maximal inspiratory effort (MIP) (cmH2O) | 50 cmH2O |
| Maximum expiratory pressure (MEP) | 118 cmH2O |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 14 Participants |
| sniff nasal inspiratory pressure (SNIP) | 39 cmH2O |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 23 |
| other Total, other adverse events | 0 / 23 | 0 / 23 |
| serious Total, serious adverse events | 0 / 23 | 0 / 23 |
Outcome results
Primary
Overnight Mean Oxygen Saturation
Overnight oximetry (SaO2) and transcutaneous capnography (PtcCO2) (TOSCA, Linde Medical Sensors, Switzerland) were performed during a sleep a on NIV at the end of each month's NIV therapy.
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Autotitrating iVAPS NIV | Overnight Mean Oxygen Saturation | 96 % SaO2 |
| Standard Non-invasive PS Ventilation | Overnight Mean Oxygen Saturation | 96 % SaO2 |
Comparison: We tested the hypothesis that iVAPS can ventilate a patient naive to NIV at least as effectively as standard PS.~Sleep and breathing parameters at the end of each treatment period were compared using Wilcoxon Signed Rank test. The median difference between treatments with 95% confidence intervals was then compared by related-samples Hodges-Lehman testp-value: 0.1395% CI: [-0.2, 1]Wilcoxon (Mann-Whitney)
Secondary
Overnight Mean Transcutaneous Carbon Dioxide
Overnight oximetry (SaO2) and transcutaneous capnography (PtcCO2) (TOSCA, Linde Medical Sensors, Switzerland) were performed during a sleep a on NIV at the end of each month's NIV therapy.
Time frame: 4 weeks
Population: All patients had a sleep study after 1 month of each mode of ventilation and all results are included in this analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Autotitrating iVAPS NIV | Overnight Mean Transcutaneous Carbon Dioxide | 6.5 kPa |
| Standard Non-invasive PS Ventilation | Overnight Mean Transcutaneous Carbon Dioxide | 6.2 kPa |
Comparison: Hypothesis: that we tested the hypothesis that iVAPS, with automated selection of ventilator settings, was non-inferior to standard pressure support (PS) ventilation, with settings determined by an experienced healthcare professional, for controlling nocturnal hypoventilation in patients naïve to NIV.p-value: 0.5495% CI: [-0.3, 0.4]Wilcoxon (Mann-Whitney)
Secondary
Overnight Peak Transcutaneous Carbon Dioxide
Overnight oximetry (SaO2) and transcutaneous capnography (PtcCO2) (TOSCA, Linde Medical Sensors, Switzerland) were performed during a sleep a on NIV at the end of each month's NIV therapy.
Time frame: 4 weeks
Population: All patients had a sleep study after 1 month of each mode of ventilation and all results are included in this analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Autotitrating iVAPS NIV | Overnight Peak Transcutaneous Carbon Dioxide | 7.1 kPa |
| Standard Non-invasive PS Ventilation | Overnight Peak Transcutaneous Carbon Dioxide | 6.9 kPa |
p-value: 0.9495% CI: [-0.5, 0.5]Wilcoxon (Mann-Whitney)
Secondary
Oxygen Desaturation Index (>4%)
Overnight oximetry (SaO2) and transcutaneous capnography (PtcCO2) (TOSCA, Linde Medical Sensors, Switzerland) were performed during a sleep a on NIV at the end of each month's NIV therapy. ODI is the number of events per hour that SaO2 drops by \>4%.
Time frame: 4 weeks
Population: All patients had a sleep study after 1 month of each mode of ventilation and all results are included in this analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Autotitrating iVAPS NIV | Oxygen Desaturation Index (>4%) | 2.5 events/hr |
| Standard Non-invasive PS Ventilation | Oxygen Desaturation Index (>4%) | 5.0 events/hr |
p-value: 0.4295% CI: [-2, 1]Wilcoxon (Mann-Whitney)
Secondary
Sleep Quality: Arousal Index
A full PSG was performed during a sleep a on NIV at the end of each month's NIV therapy. Standard polysomnography analysis was performed by two team members blinded to patient identity and ventilator mode (REP/JJ). Sleep quality was assessed by the Arousal Index (no of arousals/hour)
Time frame: 4 weeks
Population: 16 patients had comparative PSG data with all signals present for their sleep studies on both ventilator modes.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Autotitrating iVAPS NIV | Sleep Quality: Arousal Index | 17 events/hour |
| Standard Non-invasive PS Ventilation | Sleep Quality: Arousal Index | 14 events/hour |
p-value: 0.8295% CI: [-8, 4]Wilcoxon (Mann-Whitney)
Other Pre-specified
Median Overnight Minute Ventilation
Summary data from the ventilators were downloaded after each month's therapy, including adherence (hours of use), and ventilator output (nightly mean pressure support, minute ventilation (MV), RR and leak).
Time frame: 4 weeks
Population: 2 patients had missing values from one of the ventilator modes, thus were excluded from the analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Autotitrating iVAPS NIV | Median Overnight Minute Ventilation | 6.8 L/min |
| Standard Non-invasive PS Ventilation | Median Overnight Minute Ventilation | 6.2 L/min |
p-value: 0.595% CI: [-1.2, 0.5]Wilcoxon (Mann-Whitney)
Other Pre-specified
Median Overnight Pressure Support
Summary data from the ventilators were downloaded after each month's therapy, including adherence (hours of use), and ventilator output (nightly mean pressure support, minute ventilation (MV), RR and leak).
Time frame: 4 weeks
Population: 2 patients had missing data from one of the ventialtory modes and were excluded from the analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Autotitrating iVAPS NIV | Median Overnight Pressure Support | 8.3 cmH2O |
| Standard Non-invasive PS Ventilation | Median Overnight Pressure Support | 10.0 cmH2O |
p-value: 0.00195% CI: [-4.5, 0.3]Wilcoxon (Mann-Whitney)
Other Pre-specified
Median Overnight Respiratory Rated
Summary data from the ventilators were downloaded after each month's therapy, including adherence (hours of use), and ventilator output (nightly mean pressure support, minute ventilation (MV), RR and leak).
Time frame: 4 weeks
Population: 2 patients had missing data from one ventilatory mode and thus were excluded from analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Autotitrating iVAPS NIV | Median Overnight Respiratory Rated | 16.7 bpm |
| Standard Non-invasive PS Ventilation | Median Overnight Respiratory Rated | 15.5 bpm |
p-value: 0.4195% CI: [-0.7, 2.2]Wilcoxon (Mann-Whitney)
Other Pre-specified
Median Overnight Tidal Volume
Summary data from the ventilators were downloaded after each month's therapy, including adherence (hours of use), and ventilator output (nightly mean pressure support, minute ventilation (MV), RR and leak).
Time frame: 4 weeks
Population: 2 patients had missing data from one of the ventilatory modes and so were excluded
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Autotitrating iVAPS NIV | Median Overnight Tidal Volume | 421 ml |
| Standard Non-invasive PS Ventilation | Median Overnight Tidal Volume | 400 ml |
p-value: 0.4795% CI: [-54, 23]Wilcoxon (Mann-Whitney)
Other Pre-specified
Subjective Ventilation Tolerance: Ease of Use of Ventilator
Subjective tolerance of ventilator modes was assessed by 10cm visual analogue scales (VAS) in response to questions on comfort of breath, ease of falling asleep, use of ventilator, and mode preference. VAS was scored from 0-100 for each question (0 - negative and 100 -s positive)
Time frame: 4 weeks
Population: 2 patients had missing data and were thus excluded from analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Autotitrating iVAPS NIV | Subjective Ventilation Tolerance: Ease of Use of Ventilator | 90 units on a scale |
| Standard Non-invasive PS Ventilation | Subjective Ventilation Tolerance: Ease of Use of Ventilator | 86 units on a scale |
p-value: 0.5995% CI: [-5, 14]Wilcoxon (Mann-Whitney)
Other Pre-specified
Subjective Ventilator Tolerance: Comfort of Breath Delivered
Subjective tolerance of ventilator modes was assessed by 10cm visual analogue scales (VAS) in response to questions on comfort of breath, ease of falling asleep, use of ventilator, and mode preference. VAS was scored from 0-100 for each question (0 - negative and 100 -s positive)
Time frame: 4 weeks
Population: 2 patients had missing data and thus were excluded from analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Autotitrating iVAPS NIV | Subjective Ventilator Tolerance: Comfort of Breath Delivered | 73 units on a scale |
| Standard Non-invasive PS Ventilation | Subjective Ventilator Tolerance: Comfort of Breath Delivered | 72 units on a scale |
p-value: 0.3695% CI: [-5, 12]Wilcoxon (Mann-Whitney)
Other Pre-specified
Subjective Ventilator Tolerance: Ease of Falling Asleep
Subjective tolerance of ventilator modes was assessed by 10cm visual analogue scales (VAS) in response to questions on comfort of breath, ease of falling asleep, use of ventilator, and mode preference. VAS was scored from 0-100 for each question (0 - negative and 100 -s positive)
Time frame: 4 weeks
Population: 2 patients had missing data and so were excluded from analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Autotitrating iVAPS NIV | Subjective Ventilator Tolerance: Ease of Falling Asleep | 86 units on a scale |
| Standard Non-invasive PS Ventilation | Subjective Ventilator Tolerance: Ease of Falling Asleep | 79 units on a scale |
p-value: 0.5995% CI: [-5, 14]Wilcoxon (Mann-Whitney)
Other Pre-specified
Subjective Ventilator Tolerance: Liked Using Ventilator
Subjective tolerance of ventilator modes was assessed by 10cm visual analogue scales (VAS) in response to questions on comfort of breath, ease of falling asleep, use of ventilator, and mode preference. VAS was scored from 0-100 for each question (0 - negative and 100 -s positive)
Time frame: 4 weeks
Population: 2 patients had missing data, thus were excluded from analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Autotitrating iVAPS NIV | Subjective Ventilator Tolerance: Liked Using Ventilator | 81 units on a scale |
| Standard Non-invasive PS Ventilation | Subjective Ventilator Tolerance: Liked Using Ventilator | 68 units on a scale |
p-value: 0.7295% CI: [-9, 5]Wilcoxon (Mann-Whitney)
Other Pre-specified
Ventilator Adherence
Summary data from the ventilators were downloaded after each month's therapy, including adherence (hours of use), and ventilator output (nightly mean pressure support, minute ventilation (MV), RR and leak).
Time frame: 4 weeks
Population: 1 participant had missing adherence data and so was excluded from this analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Autotitrating iVAPS NIV | Ventilator Adherence | 5.40 hh:mm/day |
| Standard Non-invasive PS Ventilation | Ventilator Adherence | 4.20 hh:mm/day |
p-value: 0.000495% CI: [0.27, 1.44]Wilcoxon (Mann-Whitney)
Other Pre-specified
Ventilator Mode Preference
Subjective tolerance of ventilator modes was assessed by 10cm visual analogue scales (VAS) in response to questions on comfort of breath, ease of falling asleep, use of ventilator, and mode preference. VAS was scored from 0-100 for each question (0 - negative and 100 -s positive)
Time frame: 4 weeks