Pulmonary Disease, Chronic ObstructiveNCT04497090
Adaptive Non-invasive Ventilation to Abolish Tidal Flow Limitation
A study testing fixed-EPAP and auto-EPAP in people with Pulmonary Disease, Chronic Obstructive and Hypercapnia, run by Politecnico di Milano at 1 site in Italy.
Trial summary
This study aimed to evaluate the effects of a novel automatic non-invasive ventilation (NIV) mode that continuously adjusts expiratory positive airway pressure (EPAP) to the lowest value that abolishes tidal expiratory flow limitation. Read more about this study
- Who is it for?
- Ages 18 to 84 years
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive, Hypercapnia, Ventilator Lung
- What is being tested?
- fixed-EPAP and auto-EPAP
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteItaly
- Study dates
- 23 Oct 2014to 15 May 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 18 to 84 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- moderate to severe COPD (GOLD 2017);
- long-term users of nocturnal non-invasive ventilation for chronic hypercapnic respiratory failure;
- presence of tidal expiratory flow limitation in the supine position at an expiratory positive airway pressure of 4 cmH2O.
Who cannot join
- COPD exacerbation within the past two months;
- acute illness;
- clinical instability.
Trial locations and contacts
1 site in 1 country.
Italy1 site
Divisione di Pneumologia, Fondazione S. Maugeri, IRCCS
Lumezzane, BS
About this study
Official title: Non-invasive Ventilation With Automatic Expiratory Positive Airway Pressure Titration to Abolish Tidal Expiratory Flow Limitation in COPD Patients With Chronic Hypercapnia
This study aimed to evaluate the effects of a novel automatic non-invasive ventilation (NIV) mode that continuously adjusts expiratory positive airway pressure (EPAP) to the lowest value that abolishes tidal expiratory flow limitation. The investigators conducted a prospective, randomized, cross-over study on stable chronic obstructive pulmonary disease (COPD) patients. Patients were studied in the hospital during two non-consecutive nights while using either fixed or adaptive EPAP. The primary outcome was the transcutaneous partial pressure of carbon dioxide. Secondary outcomes were: oxygen saturation, breathing pattern, oscillatory mechanics, patient-ventilation asynchronies, sleep quality and sleep-related respiratory events.
Read the detailed description
Study design: prospective, randomized, cross-over study. Study population: moderate to severe COPD patients, long-term users of nocturnal non-invasive ventilation for chronic hypercapnic respiratory failure. Inclusion criteria: age<85 years; presence of tidal expiratory flow limitation in the supine position at an expiratory positive airway pressure of 4 cmH2O. Exclusion criteria: COPD exacerbation within the past two months; acute illness; clinical instability.
Study protocol: Patients were studied in the hospital over 2 non-consecutive nights while using either fixed or automatic EPAP.
Ventilation strategy: pressure-controlled NIV was delivered using a non-commercial version of BiPAP Synchrony Ventilator (Philips-Respironics) via an unvented facial mask (AMARA, Philips-Respironics). The ventilator evaluated the presence of tidal expiratory flow limitation by the forced oscillation technique. In the automatic-EPAP mode, the ventilator continuously adjusted EPAP to the minimum level able to abolish tidal expiratory flow limitation, with a minimum EPAP of 4 cmH2O and keeping the pressure support constant.
Measurements: During each study night, the investigators recorded transcutaneous partial pressure of carbon dioxide and oxygen saturation (TOSCA, Radiometer) continuously. Airway opening pressure, flow and volume tracings were exported from the ventilator. Full laboratory polysomnography (Alice5, Philips-Respironics) was performed according to the American Academy of Sleep Medicine recommendations.
Data analysis: the investigators compared parameters from the two nights using Wilcoxon signed-rank test. P-values <0.05 were considered statistically significant.
- Being tested
- fixed-EPAP, auto-EPAP
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Hypercapnia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fixed-EPAPDevice
In the fixed-EPAP mode, the device kept EPAP fixed at the prescribed value
auto-EPAPDevice
In the Auto-EPAP mode, the device automatically adjusted EPAP to the minimum level able to abolish tidal expiratory flow limitation.
| Study group | Role | What they receive |
|---|---|---|
| Fixed-EPAP | Active comparator | EPAP was kept fixed at the prescribed level throughout the night Receives: Device: fixed-EPAP |
| Auto-EPAP | Experimental | EPAP was continuously adjusted using the experimental approach aimed at abolishing tidal expiratory flow limitation Receives: Device: auto-EPAP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean transcutaneous partial pressure of carbon dioxide (PtcCO2)
The partial pressure of carbon dioxide measures the efficacy of ventilation. Reducing PCO2 is the aim of nocturnal non-invasive ventilation in stable COPD patients with chronic hypercapnia. PCO2 is normally measured non-invasively using a transcutaneous probe during overnight studies.
Measured: Overnight (about 8 hours)
Percent of night time spent in hypercapnia
Hypercapnia is defined as PtcCO2 > 45 mm Hg. The aim of non-invasive ventilation in stable COPD patients is to reduce the time spent with PCO2 levels above the physiological range.
Measured: Overnight (about 8 hours)
Secondary outcomes (10)
Mean peripheral oxygen saturation (SpO2)
Peripheral oxygen saturation in a non-invasive measure of oxygenation, which is routinely evaluated in sleep and ventilation trials.
Measured: Through study completion, an average of 8 hours
Desaturation
Desaturations are common complications in respiratory disorders. A desaturation is commonly defined by a reduction in SpO2 < 90%. The investigators computed the percent of night time in which SpO2 was < 90% and the Oxygen Desaturation Index (number of desaturations per hour).
Measured: Through study completion, an average of 8 hours
Number of ineffective efforts per hour (IE)
Ineffective efforts are defined as inspiratory efforts that are not supported by the ventilator. They are indicative of patient-ventilator asynchrony, they may be associated with tidal expiratory flow limitation and they increase work of breathing and cause discomfort.
Measured: Through study completion, an average of 8 hours
Sleep quality
Sleep quality is a key outcome during overnight studies. Nocturnal non-invasive ventilation may affect sleep quality in two ways: 1) it may improve it by reducing sleep-related respiratory problems; 2) it may worsen it if the ventilation mode causes discomfort to the patient. Sleep quality was evaluated by full laboratory polysomnography. Sleep stages were identified on epochs lasting 30 seconds by a trained operator blind to the study arms. Sleep quality was quantified using the following parameters: Sleep efficiency (percent of night time asleep), percentage of sleep time spent in phase 3 sleep and in REM sleep, number of awakenings per hour.
Measured: Through study completion, an average of 8 hours
EPAP
The expiratory positive airway pressure (EPAP) is the parameter that is adjusted in the experimental arm. The ventilator automatically titrates EPAP to the minimum value able to abolish expiratory flow limitation.
Measured: Through study completion, an average of 8 hours
Breathing pattern
Tidal volume, respiratory rate, minute ventilation, and inspiratory to expiratory time ratio are the breathing pattern parameters that the respiratory control system adjusts to achieve an adequate gas exchange while minimizing work of breathing. Non-invasive ventilation interacts with and supports breathing pattern.
Measured: Through study completion, an average of 8 hours
Difference between mean inspiratory and expiatory reactance
The difference between mean inspiratory and expiatory reactance is measured using the forced oscillation technique. The difference between mean inspiratory and expiratory reactance is an index of tidal expiratory flow limitation. Values > 2.8 cmH2O*s/L are indicative of tidal expiratory flow limitation.
Measured: Through study completion, an average of 8 hours
Mean inspiratory resistance
Mean inspiratory resistance is measured using the forced oscillation technique. Inspiratory resistance is an index of airway obstruction, which increases work of breathing and contributes to the development of flow limitation.
Measured: Through study completion, an average of 8 hours
Mean inspiratory reactance
Mean inspiratory reactance is measured using the forced oscillation technique.
Measured: Through study completion, an average of 8 hours
Sleep related respiratory event
During full laboratory polysomnography the respiratory activity is monitored and sleep related respiratory events are analysed, such as apneas, hypopnea, with a breakdown into central, peripheral or mixed events.
Measured: Through study completion, an average of 8 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2020
- Study start23 Oct 2014
- Primary completion15 May 2018
- Study completion15 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Disease, Chronic ObstructiveStudies 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 N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Politecnico di Milano
- Sponsor type
- University, hospital or other
- Collaborators
- Istituti Clinici Scientifici Maugeri SpA, Philips Healthcare
- Responsible party
- Principal investigator, Raffaele Dellaca, Politecnico di Milano
- Investigators
- Raffaele L Dellacà, Prof., Principal investigator, Politecnico di Milano
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04497090
- Sponsor's protocol ID
- Polimi
- Status last verified
- Jul 2020
- First submitted
- 25 Jul 2020
- Last updated
- 4 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Milesi I, Porta R, Barbano L, Cacciatore S, Vitacca M, Dellaca RL. Automatic tailoring of the lowest PEEP to abolish tidal expiratory flow limitation in seated and supine COPD patients. Respir Med. 2019 Aug;155:13-18. doi: 10.1016/j.rmed.2019.06.022. Epub 2019 Jun 23.
PubMed 31276979Zannin E, Milesi I, Porta R, Cacciatore S, Barbano L, Trentin R, Fanfulla F, Vitacca M, Dellaca RL. Effect of nocturnal EPAP titration to abolish tidal expiratory flow limitation in COPD patients with chronic hypercapnia: a randomized, cross-over pilot study. Respir Res. 2020 Nov 18;21(1):301. doi: 10.1186/s12931-020-01567-x.
PubMed 33208164
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-invasive Ventilation With Automatic Expiratory Positive Airway Pressure Titration to Abolish Tidal Expiratory Flow Limitation in COPD Patients With Chronic Hypercapnia
- ClinicalTrials.gov ID
- NCT04497090
- Acronym / sponsor ID
- Polimi
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Politecnico di MilanoUniversity, hospital or other
- Collaborators
- Istituti Clinici Scientifici Maugeri SpA, Philips Healthcare
- Study start
- 23 Oct 2014 (actual)
- Primary completion
- 15 May 2018 (actual)
- Study completion
- 15 May 2018 (actual)
- First posted
- 4 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aimed to evaluate the effects of a novel automatic non-invasive ventilation (NIV) mode that continuously adjusts expiratory positive airway pressure (EPAP) to the lowest value that abolishes tidal expiratory flow limitation. The investigators conducted a prospective, randomized, cross-over study on stable chronic obstructive pulmonary disease (COPD) patients. Patients were studied in the hospital during two non-consecutive nights while using either fixed or adaptive EPAP. The primary outcome was the transcutaneous partial pressure of carbon dioxide. Secondary outcomes were: oxygen saturation, breathing pattern, oscillatory mechanics, patient-ventilation asynchronies, sleep quality and sleep-related respiratory events.
Detailed description
Study design: prospective, randomized, cross-over study. Study population: moderate to severe COPD patients, long-term users of nocturnal non-invasive ventilation for chronic hypercapnic respiratory failure. Inclusion criteria: age<85 years; presence of tidal expiratory flow limitation in the supine position at an expiratory positive airway pressure of 4 cmH2O. Exclusion criteria: COPD exacerbation within the past two months; acute illness; clinical instability.
Study protocol: Patients were studied in the hospital over 2 non-consecutive nights while using either fixed or automatic EPAP.
Ventilation strategy: pressure-controlled NIV was delivered using a non-commercial version of BiPAP Synchrony Ventilator (Philips-Respironics) via an unvented facial mask (AMARA, Philips-Respironics). The ventilator evaluated the presence of tidal expiratory flow limitation by the forced oscillation technique. In the automatic-EPAP mode, the ventilator continuously adjusted EPAP to the minimum level able to abolish tidal expiratory flow limitation, with a minimum EPAP of 4 cmH2O and keeping the pressure support constant.
Measurements: During each study night, the investigators recorded transcutaneous partial pressure of carbon dioxide and oxygen saturation (TOSCA, Radiometer) continuously. Airway opening pressure, flow and volume tracings were exported from the ventilator. Full laboratory polysomnography (Alice5, Philips-Respironics) was performed according to the American Academy of Sleep Medicine recommendations.
Data analysis: the investigators compared parameters from the two nights using Wilcoxon signed-rank test. P-values <0.05 were considered statistically significant.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fixed-EPAP | Active comparator | Device: fixed-EPAPEPAP was kept fixed at the prescribed level throughout the night |
| Auto-EPAP | Experimental | Device: auto-EPAPEPAP was continuously adjusted using the experimental approach aimed at abolishing tidal expiratory flow limitation |
Who may qualify
- Ages
- 18 to 84 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- moderate to severe COPD (GOLD 2017);
- long-term users of nocturnal non-invasive ventilation for chronic hypercapnic respiratory failure;
- presence of tidal expiratory flow limitation in the supine position at an expiratory positive airway pressure of 4 cmH2O.
Key exclusion criteria (3 listed)
- COPD exacerbation within the past two months;
- acute illness;
- clinical instability.
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 |
|---|---|---|
| fixed-EPAPIn the fixed-EPAP mode, the device kept EPAP fixed at the prescribed value | Device | Fixed-EPAP |
| auto-EPAPIn the Auto-EPAP mode, the device automatically adjusted EPAP to the minimum level able to abolish tidal expiratory flow limitation. | Device | Auto-EPAP |
Primary outcome
Mean transcutaneous partial pressure of carbon dioxide (PtcCO2)
Time frame: Overnight (about 8 hours)
The partial pressure of carbon dioxide measures the efficacy of ventilation. Reducing PCO2 is the aim of nocturnal non-invasive ventilation in stable COPD patients with chronic hypercapnia. PCO2 is normally measured non-invasively using a transcutaneous probe during overnight studies.
Percent of night time spent in hypercapnia
Time frame: Overnight (about 8 hours)
Hypercapnia is defined as PtcCO2 > 45 mm Hg. The aim of non-invasive ventilation in stable COPD patients is to reduce the time spent with PCO2 levels above the physiological range.
10 secondary outcomes
Mean peripheral oxygen saturation (SpO2)
Time frame: Through study completion, an average of 8 hours
Desaturation
Time frame: Through study completion, an average of 8 hours
Number of ineffective efforts per hour (IE)
Time frame: Through study completion, an average of 8 hours
Sleep quality
Time frame: Through study completion, an average of 8 hours
EPAP
Time frame: Through study completion, an average of 8 hours
Breathing pattern
Time frame: Through study completion, an average of 8 hours
Difference between mean inspiratory and expiatory reactance
Time frame: Through study completion, an average of 8 hours
Mean inspiratory resistance
Time frame: Through study completion, an average of 8 hours
Mean inspiratory reactance
Time frame: Through study completion, an average of 8 hours
Sleep related respiratory event
Time frame: Through study completion, an average of 8 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2020.
- Background: PubMed 31276979Milesi I, Porta R, Barbano L, Cacciatore S, Vitacca M, Dellaca RL. Automatic tailoring of the lowest PEEP to abolish tidal expiratory flow limitation in seated and supine COPD patients. Respir Med. 2019 Aug;155:13-18. doi: 10.1016/j.rmed.2019.06.022. Epub 2019 Jun 23.
- Derived from this study: PubMed 33208164Zannin E, Milesi I, Porta R, Cacciatore S, Barbano L, Trentin R, Fanfulla F, Vitacca M, Dellaca RL. Effect of nocturnal EPAP titration to abolish tidal expiratory flow limitation in COPD patients with chronic hypercapnia: a randomized, cross-over pilot study. Respir Res. 2020 Nov 18;21(1):301. doi: 10.1186/s12931-020-01567-x.
- Individual participant dataSharing planned: No
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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.
Raffaele L Dellacà, Prof. principal investigator
Politecnico di Milano
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing fixed-EPAP and auto-EPAP in people with Pulmonary Disease, Chronic Obstructive and Hypercapnia, run by Politecnico di Milano at 1 site in Italy.
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 3 inclusion and 3 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 4 Aug 2020. 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 Italy. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Mean transcutaneous partial pressure of carbon dioxide (PtcCO2) (time frame: Overnight (about 8 hours)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04497090, which also lists 2 linked publications.
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 4 Aug 2020.