AVAPS-AE: Validation of the AVAPS AE Algorithm in Chronic Obstructive Pulmonary Disease (COPD) Patients

• Sponsor: Patrick Murphy (Other)
• Overall Status: Completed
• CT.gov ID: NCT01601977
• Collaborator: Philips Respironics (Industry)
• Enrollment: 10
• Location: 1
• Arms: 2
• Duration (Months): 16
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief 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.

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.

Condition or Disease	Intervention/Treatment	Phase
COPD; OSA	Device: AVAPS-AE; Device: Usual care	Phase 2/Phase 3

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

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Validation of the AVAPS AE Algorithm in Chronic Obstructive Pulmonary Disease: A Non-randomised Pilot Study
• Study Start Date: May 1, 2012
• Actual Primary Completion Date: Aug 1, 2013
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention AVAPS-AE	Device: AVAPS-AE; Novel ventilation mode (Omnilab - AVAPS AE algorithm)
Active Comparator: Usual care Non-invasive ventilation	Device: Usual care; Non-invasive ventilation with standard ventilator

Outcome Measures

Primary Outcome Measures

1. Control of Nocturnal Hypoventilation [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

Secondary Outcome Measures

1. Health Related Quality of Life [2 weeks]

   Severe Respiratory Insufficiency (SRI) questionnaire. Higher scores indicate better quality of life (minimum 0, maximum 100)

2. Health Related Quality of Life [6 weeks]

   Severe Respiratory Insufficiency (SRI) questionnaire. Higher scores indicate better quality of life (minimum 0, maximum 100)

3. Total Sleep Time [baseline, 6 weeks]

   Full polysomnography performed at baseline (usual device) and 6 weeks (trial device) to examine TST

4. Control of Nocturnal Hypoventilation [2 weeks]

   mean tcCO2

5. Exercise Capacity [6 weeks]

   6 minute walk test

6. Exacerbation Frequency [6 weeks]

   patient reported exacerbations following 6 weeks of device usage

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age ≥ 21

• Diagnosis of COPD

• Currently using Bilevel device for COPD-OSA overlap syndrome

• Ability to provide consent

• Documentation of medical stability by PI

Exclusion Criteria:

• 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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St Thomas' Hospital	London		United Kingdom	SE1 7EH

Sponsors and Collaborators

• Patrick Murphy
• Philips Respironics

Investigators

• Principal Investigator: Nicholas Hart, GSTT

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Patrick Murphy, Clinical Research Fellow, Guy's and St Thomas' NHS Foundation Trust
• ClinicalTrials.gov Identifier: NCT01601977
• Other Study ID Numbers: AVAPS AE in COPD; NCT01611870
• First Posted: May 18, 2012
• Last Update Posted: Aug 18, 2016
• Last Verified: Jul 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Patrick Murphy, Clinical Research Fellow, Guy's and St Thomas' NHS Foundation Trust: COPD; Respiratory failure; NIV; OSA
• Additional relevant MeSH terms: Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive

Study Results

Participant Flow

Recruitment Details	Patients approached in ventilation clinic and assessed for trial participation. Patients were recruited and scheduled for trial initiation. Once 10 patients completed the study protocol the remaining recruited patients did not start the assessment period.

Arm/Group Title	All Study Participants
Arm/Group Description	Initial study period in usual care then switched to novel ventilation with AVAPS-AE algorithm
Period Title: Overall Study
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Single arm crossover nonrandomised study
Overall Participants	10
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63 (8)
Sex: Female, Male (Count of Participants)
Female	3 30%
Male	7 70%

Outcome Measures

1. Primary Outcome

Title	Control of Nocturnal Hypoventilation
Description	transcutaneous CO2 recording from overnight sleep study whilst using the device at 6 weeks compared to baseline control when using usual device
Time Frame	baseline, 6 week assessment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Usual Care
Arm/Group Description	Single arm, open labelled study Omnilab - AVAPS AE algorithm: Nocturnal NIV via Omnilab device using the AVAPS AE algorithm	Usual care including non-invasive ventilation Usual care: usual care crossover trial, as per intervention
Measure Participants	10	10
Mean (Standard Deviation) [kPa]	6.5 (1.6)	6.7 (1.4)

2. Secondary Outcome

Title	Health Related Quality of Life
Description	Severe Respiratory Insufficiency (SRI) questionnaire. Higher scores indicate better quality of life (minimum 0, maximum 100)
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Usual Care
Arm/Group Description	Single arm, open labelled study Omnilab - AVAPS AE algorithm: Nocturnal NIV via Omnilab device using the AVAPS AE algorithm	Usual care including non-invasive ventilation Usual care: usual care crossover trial, as per intervention
Measure Participants	10	10
Mean (Standard Deviation) [units on a scale]	60 (15)	59 (16)

3. Secondary Outcome

Title	Health Related Quality of Life
Description	Severe Respiratory Insufficiency (SRI) questionnaire. Higher scores indicate better quality of life (minimum 0, maximum 100)
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Usual Care
Arm/Group Description	Single arm, open labelled study Omnilab - AVAPS AE algorithm: Nocturnal NIV via Omnilab device using the AVAPS AE algorithm	Usual care including non-invasive ventilation Usual care: usual care crossover trial, as per intervention
Measure Participants	10	10
Mean (Standard Deviation) [units on a scale]	61 (17)	59 (16)

4. Secondary Outcome

Title	Total Sleep Time
Description	Full polysomnography performed at baseline (usual device) and 6 weeks (trial device) to examine TST
Time Frame	baseline, 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Usual Care
Arm/Group Description	Single arm, open labelled study Omnilab - AVAPS AE algorithm: Nocturnal NIV via Omnilab device using the AVAPS AE algorithm	Usual care including non-invasive ventilation Usual care: usual care crossover trial, as per intervention
Measure Participants	10	10
Mean (Standard Deviation) [minutes]	330 (72)	306 (72)

5. Secondary Outcome

Title	Control of Nocturnal Hypoventilation
Description	mean tcCO2
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Usual Care
Arm/Group Description	Single arm, open labelled study Omnilab - AVAPS AE algorithm: Nocturnal NIV via Omnilab device using the AVAPS AE algorithm	Usual care including non-invasive ventilation Usual care: usual care crossover trial, as per intervention
Measure Participants	10	10
Mean (Standard Deviation) [kPa]	6.4 (1.7)	6.5 (1.4)

6. Secondary Outcome

Title	Exercise Capacity
Description	6 minute walk test
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

1 patient declined to complete the walking test

Arm/Group Title	Intervention	Usual Care
Arm/Group Description	Single arm, open labelled study Omnilab - AVAPS AE algorithm: Nocturnal NIV via Omnilab device using the AVAPS AE algorithm	Usual care including non-invasive ventilation Usual care: usual care crossover trial, as per intervention
Measure Participants	9	9
Mean (Standard Deviation) [m]	190 (63)	175 (72)

7. Secondary Outcome

Title	Exacerbation Frequency
Description	patient reported exacerbations following 6 weeks of device usage
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Usual Care
Arm/Group Description	Single arm, open labelled study Omnilab - AVAPS AE algorithm: Nocturnal NIV via Omnilab device using the AVAPS AE algorithm	Usual care including non-invasive ventilation Usual care: usual care crossover trial, as per intervention
Measure Participants	10	10
Number [exacerbations]	0	0

Adverse Events

Time Frame	Adverse event data were collected during device usage.
Adverse Event Reporting Description	All patients under went clinical review to obtain adverse event data at study assessments
Arm/Group Title	Intervention		Usual Care
Arm/Group Description	Single arm, open labelled study Omnilab - AVAPS AE algorithm: Nocturnal NIV via Omnilab device using the AVAPS AE algorithm		Usual care including non-invasive ventilation Usual care: usual care
All Cause Mortality
	Intervention		Usual Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Intervention		Usual Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Intervention		Usual Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)

Limitations/Caveats

Non-randomised controlled study

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.