Clinical trial NCT04497090: Adaptive Non-invasive Ventilation to Abolish Tidal Flow Limitation
Official title: Non-invasive Ventilation With Automatic Expiratory Positive Airway Pressure Titration to Abolish Tidal Expiratory Flow Limitation in COPD Patients With Chronic Hypercapnia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pulmonary Disease, Chronic Obstructive
Hypercapnia
Ventilator Lung
Lead sponsor: Politecnico di Milano
Sponsor class: OTHER
Collaborators: name: Istituti Clinici Scientifici Maugeri SpA
name: Philips Healthcare
First posted: 2020-08-04
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 84
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: SUPPORTIVE_CARE

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* COPD exacerbation within the past two months;
* acute illness;
* clinical instability.

Primary outcomes:
measure: Mean transcutaneous partial pressure of carbon dioxide (PtcCO2)
timeFrame: Overnight (about 8 hours)
measure: Percent of night time spent in hypercapnia
timeFrame: Overnight (about 8 hours)
Secondary outcomes:
measure: Mean peripheral oxygen saturation (SpO2)
timeFrame: Through study completion, an average of 8 hours
measure: Desaturation
timeFrame: Through study completion, an average of 8 hours
measure: Number of ineffective efforts per hour (IE)
timeFrame: Through study completion, an average of 8 hours
measure: Sleep quality
timeFrame: Through study completion, an average of 8 hours
measure: EPAP
timeFrame: Through study completion, an average of 8 hours
measure: Breathing pattern
timeFrame: Through study completion, an average of 8 hours
measure: Difference between mean inspiratory and expiatory reactance
timeFrame: Through study completion, an average of 8 hours
measure: Mean inspiratory resistance
timeFrame: Through study completion, an average of 8 hours
measure: Mean inspiratory reactance
timeFrame: Through study completion, an average of 8 hours
measure: Sleep related respiratory event
timeFrame: Through study completion, an average of 8 hours
Other outcomes:
Locations:
city: Lumezzane
country: Italy
facility: Divisione di Pneumologia, Fondazione S. Maugeri, IRCCS
state: BS
Study officials:
affiliation: Politecnico di Milano
name: Raffaele L Dellacà, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Zannin 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.