Effect of Simeox® on Residual Volume in COPD Patients With Pulmonary Hyperinflation

Official title

Prospective, Uncontrolled, Single-arm, Interventional Study With Pre-post Intervention Assessment on the Effect of the Simeox® Electro-medical Device on Residual Volume in Patients With COPD and Pulmonary Hyperinflation

Overview

Brief Summary People with severe chronic obstructive pulmonary disease (COPD) often have too much air trapped in their lungs (pulmonary hyperinflation). This makes it hard to breathe and reduces quality of life. This study tests whether a single session with a medical device called Simeox® can reduce the amount of air trapped in the lungs. Simeox® works by applying gentle intermittent negative pressure during exhalation to help air move out of the lungs more easily. Patients with severe or very severe COPD and documented hyperinflation will undergo lung function measurements before and immediately after a 20-minute Simeox® session. The main measurement is the change in residual volume (RV), which is the amount of air left in the lungs after a full exhalation. We will also measure changes in other lung volumes, breathlessness, and any side effects. This is a single-arm pilot study enrolling 23 patients at one center in Italy (ASST Lodi). The study is non-profit and has been approved by the Ethics Committee Comitato Etico Territoriale Lombardia 1 (CET Lombardia 1).

Detailed description

Detailed Description Pulmonary hyperinflation is a key pathophysiological feature of advanced chronic obstructive pulmonary disease (COPD), resulting from air trapping due to airflow obstruction and reduced elastic recoil. It is strongly associated with dyspnea, exercise intolerance, and impaired quality of life. Reducing residual volume (RV) is therefore a clinically meaningful therapeutic target in patients with severe and very severe COPD.

Simeox® is a CE-marked electro-medical device currently used in clinical practice for bronchial secretion drainage. It applies intermittent negative pressure at high frequency (6-12 Hertz, Hz) during the expiratory phase, with the aim of increasing expiratory flow velocity and promoting air mobilization. While the device is routinely used in patients with bronchial hypersecretion, its potential effect on static lung volumes in patients with hyperinflation - regardless of the presence of significant secretions - has not been systematically investigated.

This prospective, single-arm, non-controlled pilot study aims to explore the immediate effect of a single Simeox® session on RV in patients with severe or very severe COPD and documented pulmonary hyperinflation.

Study procedure:

Each participant undergoes baseline lung function assessment using spirometry and nitrogen wash-out (N₂ wash-out), followed by a single Simeox® treatment session lasting approximately 20 minutes (4 series of 10 tidal breathing cycles in a seated position, with rest breaks according to tolerance). During each breathing cycle, the patient performs slow controlled exhalations while the device applies high-frequency intermittent negative pressure modulated to the maximum tolerated intensity. Lung function measurements are repeated immediately after the session (within 30 minutes).

Safety monitoring:

Respiratory rate, heart rate, and peripheral oxygen saturation (SpO₂) are monitored throughout the session. Adverse events are recorded and classified by type, severity, and relationship to the treatment. Tolerability is assessed through subjective patient rating and dyspnea score variation.

Statistical analysis:

Pre- and post-intervention comparisons will be performed using a paired t-test or Wilcoxon signed-rank test depending on data distribution (significance level p \< 0.05). Sample size was calculated based on a clinically meaningful RV reduction of 0.40 L (standard deviation, SD: 0.60 L), yielding a minimum of 21 patients (80% power, α = 0.05), with 23 patients planned to account for dropouts.

This pilot study will provide the methodological basis for designing a future randomized controlled trial (RCT) with a larger sample and longer follow-up.

Interventions

• Device Simeox
  Single treatment session of approximately 20 minutes with the Simeox® electro-medical device. The session consists of 4 series of 10 tidal breathing cycles performed in a seated position, with rest breaks according to patient tolerance. During each breathing cycle, the patient performs slow controlled exhalations while the device applies high-frequency intermittent negative pressure (6-12 Hz), modulated to the maximum tolerated intensity. Treatment efficacy is monitored through visual indicators

Primary outcome measures

• Change in Residual Volume (RV) [Time frame: Baseline and within 30 minutes after the end of the treatment session]

Secondary outcome measures (5)

• Change in Functional Residual Capacity (FRC) [Time frame: Baseline and within 30 minutes after the end of the treatment session]
• Change in Vital Capacity (VC) [Time frame: Baseline and within 30 minutes after the end of the treatment session]
• Change in Dyspnea Score [Time frame: Baseline and within 30 minutes after the end of the treatment session]
• Incidence of Adverse Events [Time frame: From the start of the treatment session up to 30 minutes after session completion]
• Treatment Tolerability [Time frame: From the start of the treatment session up to 30 minutes after session completion]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years
• Diagnosis of severe or very severe COPD (GOLD stage 3-4)
• Documented pulmonary hyperinflation defined by at least one of the following criteria measured by nitrogen wash-out (N₂ wash-out):
• Residual volume (RV) > 150% of predicted
• Functional residual capacity (FRC) > 130% of predicted
• Total lung capacity (TLC) > 120% of predicted
• RV/TLC ratio > 40%
• Clinical stability (no exacerbations in the 3 weeks prior to enrollment)
• Patients for whom assessment of the effect of Simeox® on reduction of pulmonary hyperinflation is considered clinically appropriate, in the context of exploratory device use
• Written informed consent

Exclusion criteria

• Active or recent pneumothorax (< 6 weeks), predisposition to pneumothorax or pneumomediastinum, or known pleural fragility
• Active or recent gross haemoptysis (< 6 weeks) or active pulmonary haemorrhage
• Haemodynamic instability
• Unstable cardiovascular conditions, including:
• Recent myocardial infarction
• Unstable angina
• Uncontrolled arrhythmias
• Unstable heart failure
• Recent cardiothoracic surgery (< 3 months), including oesophageal surgery
• Recent thoracic trauma or severe acute lung injury
• Continuous mechanical ventilation, active need for inspiratory assistance, or tracheostomy
• Neuromuscular diseases with respiratory muscle weakness
• Inspiratory muscle weakness precluding increased respiratory effort
• Oropharyngeal or oral muscle weakness
• Inability to cough effectively, forcefully and autonomously
• Severe restrictive lung disease (TLC < 60% of predicted)
• Airways at risk of aspiration (e.g. recent nasogastric tube feeding)
• Uncontrolled gastro-oesophageal reflux disease (GERD)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Italy · 1 center

• ASST Lodi - Presidio Ospedaliero di Codogno — Codogno

Publications

• . Chow SC, Shao J, Wang H. Sample Size Calculations in Clinical Research. 2nd ed. Boca Raton: Chapman & Hall/CRC; 2008.
• Hartman JE, Ten Hacken NH, Klooster K, Boezen HM, de Greef MH, Slebos DJ. The minimal important difference for residual volume in patients with severe emphysema. Eur Respir J. 2012 Nov;40(5):1137-41. doi: 10.1183/09031936.00219111. Epub 2012 Mar 22. PMID 22441742
• Fessler HE, Scharf SM, Permutt S. Improvement in spirometry following lung volume reduction surgery: application of a physiologic model. Am J Respir Crit Care Med. 2002 Jan 1;165(1):34-40. doi: 10.1164/ajrccm.165.1.2101149. PMID 11779727
• Hopkinson NS, Toma TP, Hansell DM, Goldstraw P, Moxham J, Geddes DM, Polkey MI. Effect of bronchoscopic lung volume reduction on dynamic hyperinflation and exercise in emphysema. Am J Respir Crit Care Med. 2005 Mar 1;171(5):453-60. doi: 10.1164/rccm.200407-961OC. Epub 2004 Dec 3. PMID 15579725
• Wanger J, Clausen JL, Coates A, Pedersen OF, Brusasco V, Burgos F, Casaburi R, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Hankinson J, Jensen R, Johnson D, Macintyre N, McKay R, Miller MR, Navajas D, Pellegrino R, Viegi G. Standardisation of the measurement of lung volumes. Eur Respir J. 2005 Sep;26(3):511-22. doi: 10.1183/09031936.05.00035005. No abstract available. PMID 16135736
• O'Donnell DE, Laveneziana P. Dyspnea and activity limitation in COPD: mechanical factors. COPD. 2007 Sep;4(3):225-36. doi: 10.1080/15412550701480455. PMID 17729066
• Garcia-Rio F, Lores V, Mediano O, Rojo B, Hernanz A, Lopez-Collazo E, Alvarez-Sala R. Daily physical activity in patients with chronic obstructive pulmonary disease is mainly associated with dynamic hyperinflation. Am J Respir Crit Care Med. 2009 Sep 15;180(6):506-12. doi: 10.1164/rccm.200812-1873OC. Epub 2009 Jun 19. PMID 19542481
• Puente-Maestu L, Stringer WW. Hyperinflation and its management in COPD. Int J Chron Obstruct Pulmon Dis. 2006;1(4):381-400. doi: 10.2147/copd.2006.1.4.381. PMID 18044095

Identifiers

NCT: NCT07665931 · CET 100-2026

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗