Acute Respiratory FailurePhase 2/3PENSAFE-HFNCNCT06815679
Physiological Effects of Nebulized Salbutamol in Acute Respiratory Failure Patients on HFNC
A Phase 2/3 study testing salbutamol 2.5 mg via vibrating mesh nebulizer (VMN) in people with Acute Respiratory Failure and Pneumonia, run by Università degli Studi di Ferrara at 1 site in Italy.
Trial summary
This is a prospective physiological interventional study that assess the feasibility and safety of administering salbutamol using a vibrating mesh nebulizer during HFNC in patients with acute hypoxemic respiratory failure (AHRF). Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Acute Respiratory Failure, Pneumonia
- What is being tested?
- salbutamol 2.5 mg via vibrating mesh nebulizer (VMN)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- 1 Mar 2025to Jul 2026
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
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 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- • Age > 18, < 90 years
- Non-intubated critically ill patients with AHRF due to pneumonia (diagnosis is based on the presence of infiltrates on chest X-ray and the onset of clinical signs of infection less than 7 days earlier)
- PaO2/FiO2 ≤ 300 mmHg
- Patients receiving oxygen therapy
Who cannot join
- • Age < 18 years
- Hypercapnia (PaCO2 > 50 mmHg)
- Hemodynamic instability (Systolic blood pressure < 90 mmHg or Mean arterial pressure < 60 or high dose of vasoactive drugs)
- Tachycardia or tachyarrhythmia (HR > 130 b/min)
- Known allergy or intolerance to salbutamol
- Patient has received inhaled therapy with short-acting beta 2 agonists < 8 hours before or with long-acting beta 2 agonists < 24 hours before
Show all 12Show fewer
- Acute exacerbation of COPD or bronchial asthma
- Cardiogenic pulmonary edema
- GCS ≤ 12
- Contraindication for EIT (e.g. ICD)
- Pregnancy
- Patient refuses to participate
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Carlo Alberto Volta, Professor contact
Italy1 site
Azienda ospedaliera Universitaria di Ferrara
Ferrara, 44121
Savino Spadaro, Associate Professor, spdsvn@unife.it
About this study
Official title: The Physiological Effects of Nebulized Salbutamol in Patients With Acute Respiratory Failure During HFNC
This is a prospective physiological interventional study that assess the feasibility and safety of administering salbutamol using a vibrating mesh nebulizer during HFNC in patients with acute hypoxemic respiratory failure (AHRF). We evaluate whether this method of salbutamol delivery can reduce inspiratory effort and improve global and regional lung ventilation in AHRF patients. To achieve this, the study will record and analyze the following: esophageal pressure (Pes) curves, global and regional tidal volumes, minute ventilation, and changes in global and regional lung ventilation assessed through Electrical Impedance Tomography (EIT).
Read the detailed description
To evaluate the patient's respiratory effort, the pressure-time product (PTPes) and the delta of Pes oscillations during inspiration (∆ Pes) will be obtained from the analysis of the Pes curve. Global and regional pulmonary tidal volumes will be evaluated with EIT.
- Conditions
- Acute Respiratory Failure, Pneumonia
- Being tested
- salbutamol 2.5 mg via vibrating mesh nebulizer (VMN)
- Keywords
- salbutamol, acute respiratory failure, high flow nasal cannalae, aerosol delivery
- Medical subject headings
- Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
salbutamol 2.5 mg via vibrating mesh nebulizer (VMN)Drug
To evaluate the patient's respiratory effort, the pressure-time product (PTPes) and the delta of Pes oscillations during inspiration (∆ Pes) will be obtained from the analysis of the Pes curve. Global and regional pulmonary tidal volumes will be evaluated with Electrical Impedance Tomography
| Study group | Role | What they receive |
|---|---|---|
| Salbutamol | Experimental | All patients will received ventilatory support with HFNC by adjusting gas flows to 30 L/min with 100% relative humidity, heated to 37 C, adjusting FiO2 levels to maintain SpO2 between 92 and 96%. After 20 min, each patient remaining on ventilatory support with HFNC will receive administration of salbutamol 2.5 mg via the vibrating mesh nebulizer (VMN) (Aerogen Solo®, Aerogen Ltd., Galway, Ireland) positioned immediately downstream of the humidification chamber of the HFNC system, using the dedicated connector. Receives: Drug: salbutamol 2.5 mg via vibrating mesh nebulizer (VMN) |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the changes of inspiratory effort based on the analysis of the oesophageal pressure curve.
Our hypothesis is based on changes of inspiratory effort, based on the analysis of the delta esophageal pressure (ΔPes), after the administration of Salbutamol by via a vibrating mesh nebulizer during HFNC in patients with AHRF. Evaluating the delta esophageal pressure (ΔPes) requires careful measurement of esophageal pressure (Pes) during the respiratory cycle. ΔPes specifically reflects the inspiratory effort or the work of breathing (WOB), as it measures the difference between the maximum inspiratory and expiratory Pes values during each breath.
Measured: The measurement of ΔPes will be conducted: After 20 minutes of ventilatory support with HFNC (Time 0) 10 minutes following the completion of Salbutamol administration (Time 1) At 1 hour, 2 hours, and 3 hours post-Salbutamol administration
Secondary outcomes (7)
Feasibility and safety of administering salbutamol via a vibrating mesh nebulize
To evaluate the feasibility and safety of administering salbutamol via a vibrating mesh nebulizer during HFNC in patients with AHRF. The safety evaluation involves identifying and mitigating potential risks associated with the intervention.
Monitor patients for known side effects of Salbutamol, such as:
Tachycardia (>100bpm) Arrhythmias (identified by bpm; millisecond)
Continuously monitor:
Heart rate (to detect tachycardia; bpm)
Measured: Data Collection Points: Baseline (prior to Salbutamol administration). During nebulization. Post-nebulization at 10 minutes, 1 hour, 2 hours, and 3 hours.
Feasibility and safety of administering salbutamol via a vibrating mesh nebulize To evaluate the feasibility and safety of administering salbutamol via a vibrating mesh nebulizer during HFNC in patients with AHRF. The safety evaluation involves identif
To evaluate the feasibility and safety of administering salbutamol via a vibrating mesh nebulizer during HFNC in patients with AHRF. The safety evaluation involves identifying and mitigating potential risks associated with the intervention. Hypokalemia (definied <3.0 to 3.4 mEq/L)
Measured: Data Collection Points: Baseline (prior to Salbutamol administration). During nebulization. Post-nebulization at 10 minutes, 1 hour, 2 hours, and 3 hours.
Feasibility and safety of administering salbutamol via a vibrating mesh nebulize
To evaluate the feasibility and safety of administering salbutamol via a vibrating mesh nebulizer during HFNC in patients with AHRF. The safety evaluation involves identifying and mitigating potential risks associated with the intervention. Record any exacerbation of respiratory distress or intolerance to the nebulization process. Continuously monitor: Oxygen saturation (SpO₂,%) and respiratory rate (to ensure adequate oxygenation and ventilation)
Measured: [Time Frame: Data Collection Points: Baseline (prior to Salbutamol administration). During nebulization. Post-nebulization at 10 minutes, 1 hour, 2 hours, and 3 hours.]
Feasibility and safety of administering salbutamol via a vibrating mesh nebulize
To evaluate the feasibility and safety of administering salbutamol via a vibrating mesh nebulizer during HFNC in patients with AHRF. Patient Tolerance: Document patient comfort scale (from 1 to 10)
Measured: : Baseline (prior to Salbutamol administration). During nebulization. Post-nebulization at 10 minutes, 1 hour, 2 hours, and 3 hours.]
Evaluation of global and regional ventilation by EIT
To evaluate the improvement of global and regional ventilation based on data obtained with EIT after the administration of salbutamol via a vibrating mesh nebulizer during HFNC in patients with AHRF. EIT provides real-time, non-invasive monitoring of ventilation by measuring regional changes in electrical impedance within the thorax. Parameters to Monitor with EIT: Global Ventilation: Overall changes in lung ventilation during tidal breathing.
Regional Ventilation Distribution in percentage in tidal volume (%).
Measured: Data Collection Points: Baseline (before Salbutamol administration) during HFNC therapy. Post-Salbutamol: 10 minutes (early phase of response) 1 hour, 2 hours, and 3 hours after Salbutamol administration.
Evaluation of global and regional ventilation by EIT
To evaluate the improvement of regional ventilation based on data obtained with EIT after the administration of salbutamol via a vibrating mesh nebulizer during HFNC in patients with AHRF. Regional Ventilation Delay (RVD) Definition: Measures the time delay in the filling of different lung regions during inhalation.
Unit: Milliseconds (ms) or as a percentage of the respiratory cycle.
Measured: Data Collection Points: Baseline (before Salbutamol administration) during HFNC therapy. Post-Salbutamol: 10 minutes (early phase of response) 1 hour, 2 hours, and 3 hours after Salbutamol administration.
Evaluation of global and regional ventilation by EIT
To evaluate the improvement of regional ventilation based on data obtained with EIT after the administration of salbutamol via a vibrating mesh nebulizer during HFNC in patients with AHRF. Center of Ventilation (CoV) Definition: Describes the gravity-dependent distribution of ventilation from ventral (front) to dorsal (back) lung regions.
Unit: Percentage (%), representing the shift in ventilation
Measured: Data Collection Points: Baseline (before Salbutamol administration) during HFNC therapy. Post-Salbutamol: 10 minutes (early phase of response) 1 hour, 2 hours, and 3 hours after Salbutamol administration.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2025
- Study start1 Mar 2025 (estimated)
- Primary completionJan 2026 (estimated)
- Study completionJul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Acute Respiratory FailureStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Università degli Studi di Ferrara
- Sponsor type
- University, hospital or other
- Collaborators
- Aerogen
- Responsible party
- Principal investigator, Savino Spadaro, Università degli Studi di Ferrara
- Investigators
- Carlo Alberto Volta, Professor, Principal investigator, Università degli Studi di Ferrara
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06815679
- Sponsor's protocol ID
- Nebulized Salbutamol and HFNC
- Acronym
- PENSAFE-HFNC
- Status last verified
- Feb 2025
- First submitted
- 9 Jan 2025
- Last updated
- 7 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
MacLoughlin R, Mac Giolla Eain M. Performance Characterisation of the Airvo2TM Nebuliser Adapter in Combination with the Aerogen SoloTM Vibrating Mesh Nebuliser for in Line Aerosol Therapy during High Flow Nasal Oxygen Therapy. Pharmaceutics. 2024 Apr 20;16(4):565. doi: 10.3390/pharmaceutics16040565.
PubMed 38675226Calabrese C, Annunziata A, Mariniello DF, Allocca V, Imitazione P, Cauteruccio R, Simioli F, Fiorentino G. Aerosol delivery through high-flow nasal therapy: Technical issues and clinical benefits. Front Med (Lausanne). 2023 Jan 18;9:1098427. doi: 10.3389/fmed.2022.1098427. eCollection 2022.
PubMed 36743674Arunsurat I, Rittayamai N, Chuaychoo B, Tangchityongsiva S, Promsarn S, Yuenyong S, Chow CW, Brochard L. Bronchodilator Efficacy of High-Flow Nasal Cannula in COPD: Vibrating Mesh Nebulizer Versus Jet Nebulizer. Respir Care. 2024 Jan 24;69(2):157-165. doi: 10.4187/respcare.11139.
PubMed 37607815
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Physiological Effects of Nebulized Salbutamol in Patients With Acute Respiratory Failure During HFNC
- ClinicalTrials.gov ID
- NCT06815679
- Acronym / sponsor ID
- PENSAFE-HFNC / Nebulized Salbutamol and HFNC
- Conditions
- Acute Respiratory Failure, Pneumonia
- Keywords
- salbutamol, acute respiratory failure, high flow nasal cannalae, aerosol delivery
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Università degli Studi di FerraraUniversity, hospital or other
- Collaborators
- Aerogen
- Study start
- 1 Mar 2025 (estimated)
- Primary completion
- Jan 2026 (estimated)
- Study completion
- Jul 2026 (estimated)
- First posted
- 7 Feb 2025 (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 is a prospective physiological interventional study that assess the feasibility and safety of administering salbutamol using a vibrating mesh nebulizer during HFNC in patients with acute hypoxemic respiratory failure (AHRF). We evaluate whether this method of salbutamol delivery can reduce inspiratory effort and improve global and regional lung ventilation in AHRF patients. To achieve this, the study will record and analyze the following: esophageal pressure (Pes) curves, global and regional tidal volumes, minute ventilation, and changes in global and regional lung ventilation assessed through Electrical Impedance Tomography (EIT).
Detailed description
To evaluate the patient's respiratory effort, the pressure-time product (PTPes) and the delta of Pes oscillations during inspiration (∆ Pes) will be obtained from the analysis of the Pes curve. Global and regional pulmonary tidal volumes will be evaluated with EIT.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Salbutamol | Experimental | Drug: salbutamol 2.5 mg via vibrating mesh nebulizer (VMN)All patients will received ventilatory support with HFNC by adjusting gas flows to 30 L/min with 100% relative humidity, heated to 37 C, adjusting FiO2 levels to maintain SpO2 between 92 and 96%. After 20 min, each patient remaining on ventilatory support with HFNC will receive administration of salbutamol 2.5 mg via the vibrating mesh nebulizer (VMN) (Aerogen Solo®, Aerogen Ltd., Galway, Ireland) positioned immediately downstream of the humidification chamber of the HFNC system, using the dedicated connector. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- • Age > 18, < 90 years
Key exclusion criteria (12 listed)
- • Age < 18 years
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 |
|---|---|---|
| salbutamol 2.5 mg via vibrating mesh nebulizer (VMN)To evaluate the patient's respiratory effort, the pressure-time product (PTPes) and the delta of Pes oscillations during inspiration (∆ Pes) will be obtained from the analysis of the Pes curve. Global and regional pulmonary tidal volumes will be evaluated with Electrical Impedance Tomography | Drug | Salbutamol |
Primary outcome
To evaluate the changes of inspiratory effort based on the analysis of the oesophageal pressure curve.
Time frame: The measurement of ΔPes will be conducted: After 20 minutes of ventilatory support with HFNC (Time 0) 10 minutes following the completion of Salbutamol administration (Time 1) At 1 hour, 2 hours, and 3 hours post-Salbutamol administration
Our hypothesis is based on changes of inspiratory effort, based on the analysis of the delta esophageal pressure (ΔPes), after the administration of Salbutamol by via a vibrating mesh nebulizer during HFNC in patients with AHRF. Evaluating the delta esophageal pressure (ΔPes) requires careful measurement of esophageal pressure (Pes) during the respiratory cycle. ΔPes specifically reflects the inspiratory effort or the work of breathing (WOB), as it measures the difference between the maximum inspiratory and expiratory Pes values during each breath.
7 secondary outcomes
Feasibility and safety of administering salbutamol via a vibrating mesh nebulize
Time frame: Data Collection Points: Baseline (prior to Salbutamol administration). During nebulization. Post-nebulization at 10 minutes, 1 hour, 2 hours, and 3 hours.
Feasibility and safety of administering salbutamol via a vibrating mesh nebulize To evaluate the feasibility and safety of administering salbutamol via a vibrating mesh nebulizer during HFNC in patients with AHRF. The safety evaluation involves identif
Time frame: Data Collection Points: Baseline (prior to Salbutamol administration). During nebulization. Post-nebulization at 10 minutes, 1 hour, 2 hours, and 3 hours.
Feasibility and safety of administering salbutamol via a vibrating mesh nebulize
Time frame: [Time Frame: Data Collection Points: Baseline (prior to Salbutamol administration). During nebulization. Post-nebulization at 10 minutes, 1 hour, 2 hours, and 3 hours.]
Feasibility and safety of administering salbutamol via a vibrating mesh nebulize
Time frame: : Baseline (prior to Salbutamol administration). During nebulization. Post-nebulization at 10 minutes, 1 hour, 2 hours, and 3 hours.]
Evaluation of global and regional ventilation by EIT
Time frame: Data Collection Points: Baseline (before Salbutamol administration) during HFNC therapy. Post-Salbutamol: 10 minutes (early phase of response) 1 hour, 2 hours, and 3 hours after Salbutamol administration.
Evaluation of global and regional ventilation by EIT
Time frame: Data Collection Points: Baseline (before Salbutamol administration) during HFNC therapy. Post-Salbutamol: 10 minutes (early phase of response) 1 hour, 2 hours, and 3 hours after Salbutamol administration.
Evaluation of global and regional ventilation by EIT
Time frame: Data Collection Points: Baseline (before Salbutamol administration) during HFNC therapy. Post-Salbutamol: 10 minutes (early phase of response) 1 hour, 2 hours, and 3 hours after Salbutamol administration.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2025.
- Results publication: PubMed 38675226MacLoughlin R, Mac Giolla Eain M. Performance Characterisation of the Airvo2TM Nebuliser Adapter in Combination with the Aerogen SoloTM Vibrating Mesh Nebuliser for in Line Aerosol Therapy during High Flow Nasal Oxygen Therapy. Pharmaceutics. 2024 Apr 20;16(4):565. doi: 10.3390/pharmaceutics16040565.
- Results publication: PubMed 36743674Calabrese C, Annunziata A, Mariniello DF, Allocca V, Imitazione P, Cauteruccio R, Simioli F, Fiorentino G. Aerosol delivery through high-flow nasal therapy: Technical issues and clinical benefits. Front Med (Lausanne). 2023 Jan 18;9:1098427. doi: 10.3389/fmed.2022.1098427. eCollection 2022.
- Results publication: PubMed 37607815Arunsurat I, Rittayamai N, Chuaychoo B, Tangchityongsiva S, Promsarn S, Yuenyong S, Chow CW, Brochard L. Bronchodilator Efficacy of High-Flow Nasal Cannula in COPD: Vibrating Mesh Nebulizer Versus Jet Nebulizer. Respir Care. 2024 Jan 24;69(2):157-165. doi: 10.4187/respcare.11139.
- Individual participant dataSharing planned: No
Related trials for Acute Respiratory Failure
Enrolling by invitation
Personalized Ventilator Settings for Patients on ECMO
Acute Respiratory Distress Syndrome (ARDS), Extracorporeal Membrane Oxygenation
Not yet recruiting
Regional Lung Ventilation During Prone Position in in Intubated Children
Pediatric Acute Respiratory Failure
Not yet recruiting
Influence of Patient Positioning During Nasal Lavage
Acute Upper Respiratory Tract Infections, Nasal Obstruction
Recruiting
WIN Ratio Analysis to Determine a Strategy of Non- Invasive SUpport for Respiratory Failure in the EmeRgency Department
Acute Hypoxic Respiratory Failure, Acute Respiratory Distress Syndrome (ARDS)
Not yet recruiting
ICU-SUCCEED for Survivors of Acute Respiratory Failure and Their Caregivers
Acute Respiratory Failure, Critical Illness
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.
Carlo Alberto Volta, Professor contact
Carlo Alberto Volta, Professor principal investigator
Università degli Studi di Ferrara
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 salbutamol 2.5 mg via vibrating mesh nebulizer (VMN) in people with Acute Respiratory Failure and Pneumonia, run by Università degli Studi di Ferrara 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 4 inclusion and 12 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: opening soon, as of the sponsor's last update on 7 Feb 2025. 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.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Savino Spadaro, Associate professor (+39 0532 293111, spdsvn@unife.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the changes of inspiratory effort based on the analysis of the oesophageal pressure curve. (time frame: The measurement of ΔPes will be conducted: After 20 minutes of ventilatory support with HFNC (Time 0) 10 minutes following the completion of Salbutamol administration (Time 1) At 1 hour, 2 hours, and 3 hours post-Salbutamol administration). 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 NCT06815679, which also lists 3 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 7 Feb 2025.