COPDPhase 2/3AVAPS-AENCT01601977
Validation of the AVAPS AE Algorithm in Chronic Obstructive Pulmonary Disease (COPD) Patients
A Phase 2/3 study testing AVAPS-AE in people with COPD and OSA, run by Patrick Murphy at 1 site in United Kingdom.
Trial summary
COPD continues to be a cause of major morbidity for patients. Those patients who also have respiratory failure and obstructive sleep apnoea are at higher risk of exacerbations and death and have worse health related quality of life than similar COPD patients without respiratory failure. Read more about this study
- Who is it for?
- Ages 21 to 90 years
- What is being tested?
- AVAPS-AE
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- May 2012to Sep 2013
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 21
- Diagnosis of COPD
- Currently using Bilevel device for COPD-OSA overlap syndrome
- Ability to provide consent
- Documentation of medical stability by PI
Who cannot join
- Subjects, who are acutely ill, medically complicated or who are medically unstable.
- Subjects in whom PAP therapy is otherwise medically contraindicated.
- Subjects who have had surgery of the upper airway, nose, sinus, or middle ear within the previous 90 days.
- Subjects with untreated, non-OSA sleep disorders, including but not limited to; insomnia, periodic limb movement syndrome, or restless legs syndrome (PLMI > 10).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Validation of the AVAPS AE Algorithm in Chronic Obstructive Pulmonary Disease: A Non-randomised Pilot Study
COPD continues to be a cause of major morbidity for patients. Those patients who also have respiratory failure and obstructive sleep apnoea are at higher risk of exacerbations and death and have worse health related quality of life than similar COPD patients without respiratory failure.
Treatment options in this group of patients have been limited and data to support the use of machines to assist breathing (non-invasive ventilators) in stable patients are limited. A major limitation of these devices has been patient acceptance and achieving sufficient control of sleep breathing disturbance.
Currently devices are set at a fixed pressure to support the breathing throughout the night. The new software within the trial device will aim to better match the support provided by the machine to that needed by the patient. It is hoped that this may offer enhanced comfort as well as superior control of respiratory failure.
Read the detailed description
Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality worldwide.
Treatment options for COPD patients consist of medications, such as bronchodilators and anti-inflammatory drugs, pulmonary rehabilitation, long term oxygen therapy (LTOT), lung volume reduction surgery and lung transplantation. Studies have shown that bronchodilators and anti-inflammatory drugs show minor or no benefit on long term outcomes but rather are used mainly for symptomatic relief.1 Pulmonary rehabilitation has been demonstrated to improve functional status and symptoms but there is lacking evidence on long term outcomes of this therapy. 2 Lung volume reduction surgery and lung transplantation is only appropriate for a small number of patients; therefore, there is no demonstration of improved long-term survival rate.3, 4
Of these available therapies, few have been shown to significantly improve long term patient outcomes. For the severe COPD patient, LTOT is the only treatment that demonstrated prolonged survival in controlled studies. 5, 6 But, despite the effectiveness of LTOT, COPD is still characterized by a high morbidity and mortality rate.
Although the treatment of OSA with CPAP therapy has been associated with reduced hospital admissions and exacerbations there are possible adverse consequences on pulmonary mechanics due to exacerbating hyperinflation.
Noninvasive positive pressure ventilation (NPPV) is one therapy that may prove beneficial to stable COPD patients. NPPV is the use of positive pressure ventilation administered via a nasal or full face mask (that covers both the nose and mouth). This type of ventilation has become a well established and increasingly used therapeutic option for patients with hypercapnic respiratory failure (HRF) due to COPD.7
NPPV, used nocturnally, may improve nighttime hypoventilation that is common with COPD patients. An improvement in nocturnal hypoventilation would reset the respiratory center sensitivity for CO2.8 9 This would result in an improvement in daytime gas exchange and sleep quality. It is also known that hyperinflation in patients with COPD increases their work of breathing, thus fatiguing the respiratory muscles.10 It has been suggested that by applying nocturnal NPPV it would allow the respiratory muscles to rest, resulting in muscle function recovery, increased muscle strength, reduced tendency for fatigue and improvement in pulmonary function and gas exchange.11
AVAPS AE AVAPS AE is a mode of therapy (Philips Respironics Inc, Monroeville, PA, USA) with potential advantages over the currently established modes of noninvasive positive pressure ventilation (CPAP and bilevel therapy). This mode of therapy incorporates AVAPS (automated adjustable IPAP setting to maintain target ventilation with a settable rate of change), AutoEPAP and Auto Back up Rate. In particular the automated EPAP algorithm will ensure optimal upper airway patency without exacerbating hyperinflation.
In this study, we are evaluating the AVAPS AE mode as compared to the participant's current mode of ventilation. We believe that these automated parameters will allow better nocturnal ventilatory control to offset the differing elastic and resistive loads imposed by changes in body position during sleep. Furthermore, AVAPS AE will counter the changing ventilatory requirements due to alterations in lung volumes and airway resistance during different stages of sleep. In summary, the AVAPS AE mode will enable automatic adjustment in response to ventilatory changes throughout the night.
Study Objective The objective of this study is to validate the performance of the AVAPS AE therapy in COPD-OSA overlap patients during nocturnal ventilation.
- Being tested
- AVAPS-AE, Usual care
- Keywords
- COPD, Respiratory failure, NIV, OSA
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AVAPS-AEDevice
Novel ventilation mode (Omnilab - AVAPS AE algorithm)
Usual careDevice
Non-invasive ventilation with standard ventilator
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | AVAPS-AE Receives: Device: AVAPS-AE |
| Usual care | Active comparator | Non-invasive ventilation Receives: Device: Usual care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Control of Nocturnal Hypoventilation
transcutaneous CO2 recording from overnight sleep study whilst using the device at 6 weeks compared to baseline control when using usual device
Measured: baseline, 6 week assessment
Secondary outcomes (6)
Health Related Quality of Life
Severe Respiratory Insufficiency (SRI) questionnaire. Higher scores indicate better quality of life (minimum 0, maximum 100)
Measured: 2 weeks
Health Related Quality of Life
Severe Respiratory Insufficiency (SRI) questionnaire. Higher scores indicate better quality of life (minimum 0, maximum 100)
Measured: 6 weeks
Total Sleep Time
Full polysomnography performed at baseline (usual device) and 6 weeks (trial device) to examine TST
Measured: baseline, 6 weeks
Control of Nocturnal Hypoventilation
mean tcCO2
Measured: 2 weeks
Exercise Capacity
6 minute walk test
Measured: 6 weeks
Exacerbation Frequency
patient reported exacerbations following 6 weeks of device usage
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2012 (estimated)
- Study startMay 2012
- Primary completionAug 2013
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for COPDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Patrick Murphy
- Sponsor type
- University, hospital or other
- Collaborators
- Philips Respironics
- Responsible party
- Sponsor-investigator, Patrick Murphy, Guy's and St Thomas' NHS Foundation Trust
- Investigators
- Nicholas Hart, Principal investigator, GSTT
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01601977
- Sponsor's protocol ID
- AVAPS AE in COPD
- Acronym
- AVAPS-AE
- Status last verified
- Jul 2016
- First submitted
- 17 May 2012
- Last updated
- 18 Aug 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Validation of the AVAPS AE Algorithm in Chronic Obstructive Pulmonary Disease: A Non-randomised Pilot Study
- ClinicalTrials.gov ID
- NCT01601977
- Acronym / sponsor ID
- AVAPS-AE / AVAPS AE in COPD
- Keywords
- COPD, Respiratory failure, NIV, OSA
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Patrick MurphyUniversity, hospital or other
- Collaborators
- Philips Respironics
- Study start
- May 2012
- Primary completion
- Aug 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 18 May 2012 (estimated)
- Results
- Posted 18 Aug 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
COPD continues to be a cause of major morbidity for patients. Those patients who also have respiratory failure and obstructive sleep apnoea are at higher risk of exacerbations and death and have worse health related quality of life than similar COPD patients without respiratory failure.
Treatment options in this group of patients have been limited and data to support the use of machines to assist breathing (non-invasive ventilators) in stable patients are limited. A major limitation of these devices has been patient acceptance and achieving sufficient control of sleep breathing disturbance.
Currently devices are set at a fixed pressure to support the breathing throughout the night. The new software within the trial device will aim to better match the support provided by the machine to that needed by the patient. It is hoped that this may offer enhanced comfort as well as superior control of respiratory failure.
Detailed description
Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality worldwide.
Treatment options for COPD patients consist of medications, such as bronchodilators and anti-inflammatory drugs, pulmonary rehabilitation, long term oxygen therapy (LTOT), lung volume reduction surgery and lung transplantation. Studies have shown that bronchodilators and anti-inflammatory drugs show minor or no benefit on long term outcomes but rather are used mainly for symptomatic relief.1 Pulmonary rehabilitation has been demonstrated to improve functional status and symptoms but there is lacking evidence on long term outcomes of this therapy. 2 Lung volume reduction surgery and lung transplantation is only appropriate for a small number of patients; therefore, there is no demonstration of improved long-term survival rate.3, 4
Of these available therapies, few have been shown to significantly improve long term patient outcomes. For the severe COPD patient, LTOT is the only treatment that demonstrated prolonged survival in controlled studies. 5, 6 But, despite the effectiveness of LTOT, COPD is still characterized by a high morbidity and mortality rate.
Although the treatment of OSA with CPAP therapy has been associated with reduced hospital admissions and exacerbations there are possible adverse consequences on pulmonary mechanics due to exacerbating hyperinflation.
Noninvasive positive pressure ventilation (NPPV) is one therapy that may prove beneficial to stable COPD patients. NPPV is the use of positive pressure ventilation administered via a nasal or full face mask (that covers both the nose and mouth). This type of ventilation has become a well established and increasingly used therapeutic option for patients with hypercapnic respiratory failure (HRF) due to COPD.7
NPPV, used nocturnally, may improve nighttime hypoventilation that is common with COPD patients. An improvement in nocturnal hypoventilation would reset the respiratory center sensitivity for CO2.8 9 This would result in an improvement in daytime gas exchange and sleep quality. It is also known that hyperinflation in patients with COPD increases their work of breathing, thus fatiguing the respiratory muscles.10 It has been suggested that by applying nocturnal NPPV it would allow the respiratory muscles to rest, resulting in muscle function recovery, increased muscle strength, reduced tendency for fatigue and improvement in pulmonary function and gas exchange.11
AVAPS AE AVAPS AE is a mode of therapy (Philips Respironics Inc, Monroeville, PA, USA) with potential advantages over the currently established modes of noninvasive positive pressure ventilation (CPAP and bilevel therapy). This mode of therapy incorporates AVAPS (automated adjustable IPAP setting to maintain target ventilation with a settable rate of change), AutoEPAP and Auto Back up Rate. In particular the automated EPAP algorithm will ensure optimal upper airway patency without exacerbating hyperinflation.
In this study, we are evaluating the AVAPS AE mode as compared to the participant's current mode of ventilation. We believe that these automated parameters will allow better nocturnal ventilatory control to offset the differing elastic and resistive loads imposed by changes in body position during sleep. Furthermore, AVAPS AE will counter the changing ventilatory requirements due to alterations in lung volumes and airway resistance during different stages of sleep. In summary, the AVAPS AE mode will enable automatic adjustment in response to ventilatory changes throughout the night.
Study Objective The objective of this study is to validate the performance of the AVAPS AE therapy in COPD-OSA overlap patients during nocturnal ventilation.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Device: AVAPS-AEAVAPS-AE |
| Usual care | Active comparator | Device: Usual careNon-invasive ventilation |
Who may qualify
- Ages
- 21 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age ≥ 21
- Diagnosis of COPD
- Currently using Bilevel device for COPD-OSA overlap syndrome
- Ability to provide consent
- Documentation of medical stability by PI
Key exclusion criteria (4 listed)
- Subjects, who are acutely ill, medically complicated or who are medically unstable.
- Subjects in whom PAP therapy is otherwise medically contraindicated.
- Subjects who have had surgery of the upper airway, nose, sinus, or middle ear within the previous 90 days.
- Subjects with untreated, non-OSA sleep disorders, including but not limited to; insomnia, periodic limb movement syndrome, or restless legs syndrome (PLMI > 10).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AVAPS-AENovel ventilation mode (Omnilab - AVAPS AE algorithm) | Device | Intervention |
| Usual careNon-invasive ventilation with standard ventilator | Device | Usual care |
Primary outcome
Control of Nocturnal Hypoventilation
Time frame: baseline, 6 week assessment
transcutaneous CO2 recording from overnight sleep study whilst using the device at 6 weeks compared to baseline control when using usual device
6 secondary outcomes
Health Related Quality of Life
Time frame: 2 weeks
Health Related Quality of Life
Time frame: 6 weeks
Total Sleep Time
Time frame: baseline, 6 weeks
Control of Nocturnal Hypoventilation
Time frame: 2 weeks
Exercise Capacity
Time frame: 6 weeks
Exacerbation Frequency
Time frame: 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicholas Hart principal investigator
GSTT
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing AVAPS-AE in people with COPD and OSA, run by Patrick Murphy at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Aug 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Control of Nocturnal Hypoventilation (time frame: baseline, 6 week assessment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2016.