Acute Hypoxemic Respiratory FailureTEMANCT06921655
Targeting prEssure-Muscle-index to Avoid Ventilatory Over-Assistance During Pressure Support Ventilation
A study testing Variation of Pressure Support Levels in people with Acute Hypoxemic Respiratory Failure and Mechanical Ventilation Complication, run by Centre for Medical Sciences at 1 site in Italy.
Trial summary
The TEMA study (Targeting prEssure-Muscle-index to avoid ventilatory over-Assistance during pressure support ventilation) is a prospective, interventional crossover trial investigating the relationship between pressure support (PS) and tidal volume (Vt) in ICU patients with acute hypoxemic respiratory failure (AHRF)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Hypoxemic Respiratory Failure, Mechanical Ventilation Complication
- What is being tested?
- Variation of Pressure Support Levels
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteItaly
- Study dates
- 8 Oct 2025to 15 Dec 2028
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Mechanically ventilated in the ICU
- Diagnosis of Acute Hypoxemic Respiratory Failure (AHRF)
- Normocapnia or non-severe hypercapnia
- Receiving Pressure Support Ventilation (PSV) for at least 24-72 hours
- Presence of an arterial line for blood gas sampling
Who cannot join
- Age < 18 years
- Known neurological or neuromuscular disorders affecting diaphragm function
- Chronic Obstructive Pulmonary Disease (COPD) or hypercapnic respiratory failure
- Psychomotor agitation or inadequate sedation
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Santa Chiara Hospital, Trento, Trentino-Alto Adige, Italy
Trento, Trento, 38122
Giacomo Bellani, MD, PhD, + 39 0461 903298, giacomo.bellani@unitn.it
Eleonora Balzani, MD, eleonora.balzani@unitn.it
About this study
Official title: Targeting prEssure-Muscle-index to Avoid Ventilatory Over-Assistance During Pressure
The TEMA study (Targeting prEssure-Muscle-index to avoid ventilatory over-Assistance during pressure support ventilation) is a prospective, interventional crossover trial investigating the relationship between pressure support (PS) and tidal volume (Vt) in ICU patients with acute hypoxemic respiratory failure (AHRF) receiving pressure support ventilation (PSV). The study aims to assess whether the Pressure-Muscle Index (PMI)-a marker derived from the difference between plateau and peak inspiratory pressure-can help identify the optimal level of ventilatory assistance, preventing over-assistance and its associated complications such as diaphragm atrophy and patient self-inflicted lung injury (P-SILI). By exploring the sigmoidal relationship between PS and Vt, the study seeks to define a physiological threshold (PMI=0) that may serve as a personalized target for PSV titration.
Read the detailed description
The TEMA study is a prospective, interventional crossover trial designed to explore the physiological relationship between levels of pressure support (PS) and tidal volume (Vt) in mechanically ventilated ICU patients diagnosed with acute hypoxemic respiratory failure (AHRF). The goal is to identify a pressure support threshold beyond which over-assistance occurs, leading to excessive tidal volumes and suppression of respiratory muscle activity.
The central hypothesis is that the PS-Vt curve follows a sigmoidal pattern: an initial plateau phase with stable Vt is followed by a steep, compliance-driven increase in Vt at higher PS levels. The Pressure-Muscle Index (PMI), calculated as the difference between plateau pressure (Pplat) and peak airway pressure (Ppeak) during an inspiratory occlusion, is used to define this inflection point (PMI=0), which marks the transition from physiologically appropriate to excessive assistance.
Study Design: The study is conducted at the ICU of Santa Chiara Hospital (Trento, Italy) and includes seven levels of pressure support modulation-three above and three below the identified PMI=0 point. At each level, key physiological variables such as Vt, respiratory rate (RR), minute ventilation, PMI, and patient-ventilator asynchrony index are recorded.
A second evaluation between days 4-6 post-enrollment is planned for patients who remain intubated, to assess whether the PS-Vt relationship evolves over time, reflecting changes in respiratory drive and mechanics during the ICU course.
Technical Aspects:
Measurements include respiratory system compliance, work of breathing (WOB), inspiratory effort, and occlusion-based indices.
PS levels are applied in randomized order to minimize bias. Clinical PSV settings are reinstated between steps to avoid carryover effects and ensure patient safety.
Analytical Approach: The primary outcome is to characterize the PS-Vt relationship and validate the use of PMI as a physiological marker of the optimal support threshold. Nonlinear regression models, including sigmoidal curve fitting, will be used to identify inflection points (c parameters) in the PS-Vt curve. A Monte Carlo simulation informed the sample size, targeting 36 patients to account for potential dropouts, ensuring >90% power to detect a meaningful breakpoint.
Multivariable models will adjust for potential confounders such as PaCO₂, sedation depth, BMI, and baseline compliance.
Expected Impact: If successful, the TEMA study will provide a new physiologically grounded framework for tailoring pressure support in assisted ventilation. By validating PMI as a real-time bedside tool, the study may support a more personalized approach to weaning and ventilation management, potentially improving outcomes such as duration of ventilation, weaning success, and ICU stay.
- Being tested
- Variation of Pressure Support Levels
- Keywords
- Pressure Support, Tidal Volume, Acute Hypoxemic Respiratory Failure
- Medical subject headings
- Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Variation of Pressure Support LevelsProcedure or surgery
Patients will undergo six randomized PS levels (+2, +4, +6 cmH₂O above and -2, -4, -6 cmH₂O below PSPMI=0).
| Study group | Role | What they receive |
|---|---|---|
| Pressure Support PMI=0 | Experimental | The PS level at which PMI is zeroed, meaning the patient's inspiratory effort contributes minimally to tidal volume Receives: Procedure: Variation of Pressure Support Levels |
| Pressure Support +2 | Experimental | Above PSPMI=0: +2 cmH₂O above PSPMI=0 (over-assistance zone). Receives: Procedure: Variation of Pressure Support Levels |
| Pressure Support +4 | Experimental | Above PSPMI=0: +4 cmH₂O above PSPMI=0 (over-assistance zone). Receives: Procedure: Variation of Pressure Support Levels |
| Pressure Support +6 | Experimental | Above PSPMI=0: +6 cmH₂O above PSPMI=0 (over-assistance zone). Receives: Procedure: Variation of Pressure Support Levels |
| Pressure Support -2 | Experimental | Below PSPMI=0: -2 cmH₂O below PSPMI=0 (under-assistance zone). Receives: Procedure: Variation of Pressure Support Levels |
| Pressure Support -4 | Experimental | - Below PSPMI=0: -4 cmH₂O below PSPMI=0 (under-assistance zone). Receives: Procedure: Variation of Pressure Support Levels |
| Pressure Support -6 | Experimental | - Below PSPMI=0: -6 cmH₂O below PSPMI=0 (under-assistance zone). Receives: Procedure: Variation of Pressure Support Levels |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pressure Support-Tidal Volume (PS-Vt) Relationship
The primary aim is to determine whether the PS-Vt curve exhibits a flat region (where tidal volume remains stable) before transitioning into a steep, compliance-dependent increase at higher PS levels. This transition point, identified as PSPMI=0, is hypothesized to represent the threshold for over-assistance.
Measured: Up to 5 minutes after each PS level adjustment during the interventional phase (Day 1)
Secondary outcomes (11)
Validation of Pressure-Muscle Index (PMI) as an Over-Assistance Marker
PMI will be tested as a real-time bedside indicator for detecting over-assistance in PSV. The study will assess whether PMI=0 reliably corresponds to the threshold of over-assistance, characterized by a minimal patient contribution to Vt and a linear increase in Vt proportional to PS.
Measured: Up to 5 minutes after each PS level adjustment during the interventional phase (Day 1) and during follow-up assessment on Days 4-6 (if patient remains intubated)
Impact of Respiratory Mechanics on PS-Vt Relationship
Evaluation of how respiratory compliance (Crs) influence the PS-Vt curve. The study will investigate individual variations in ventilatory response to PS.
Measured: During the interventional phase on Day 1 and during follow-up assessment on Days 4-6 (if patient remains intubated)
Rate of Ineffective Efforts During Over-Assistance
Quantification of ineffective respiratory efforts (i.e., inspiratory efforts not followed by ventilator-triggered breaths) during PS levels exceeding the identified PSPMI=0 threshold.
Measured: Up to 5 minutes after each PS level adjustment during the interventional phase (Day 1) and during follow-up assessment on Days 4-6 (if patient remains intubated)
Effect of Over-Assistance on Ventilatory Asynchronies
Measurement of the asynchrony index (percentage of breaths with any form of patient-ventilator asynchrony) at different levels of pressure support, particularly above PSPMI=0.
Measured: Up to 5 minutes after each PS level adjustment during the interventional phase (Day 1) and during follow-up assessment on Days 4-6 (if patient remains intubated)
Weaning failure
Defined as the inability to transition from PSV to unassisted breathing, requiring either reintubation, prolonged PSV dependence, or failure of a spontaneous breathing trial (SBT). The rate of weaning failure will be compared between patients receiving higher vs. lower levels of PSV support.
Measured: Up to 100 months or until the of death from any cause, whichever came first.
Duration of mechanical ventilation
Total number of days on invasive mechanical ventilation (IMV), including both fully controlled and pressure-supported modes. The study will compare patients requiring different levels of PSV assistance.
Measured: From date of randomization until the date of extubation or date of death from any cause, whichever came first, assessed up to 100 months
ICU length of stay (LOS)
Total duration (in days) of ICU admission, analyzing whether PSV settings influence prolonged ICU stays due to delayed weaning, respiratory complications, or ventilatory asynchronies
Measured: Up to 100 months or until the of death from any cause, whichever came first.
Hospital length of stay (LOS)
Total number of days spent in the hospital from admission to discharge, evaluating whether PSV-related ventilatory strategies impact overall hospitalization duration and recovery time.
Measured: Up to 100 months or until the of death from any cause, whichever came first.
Impact of Respiratory Mechanics on PS-Vt Relationship
Evaluation of how respiratory drive influence the PS-Vt curve. The study will investigate individual variations in ventilatory response to PS.
Measured: From the randomization to 5 minutes.
Impact of Respiratory Mechanics on PS-Vt Relationship
Evaluation of how patient effort (Pmus) influence the PS-Vt curve. The study will investigate individual variations in ventilatory response to PS.
Measured: From the randomization to 5 minutes.
Spontaneous breathing failure
Defined as the Number of Participants who fail transition from PCV to PSV.
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2025
- Study start8 Oct 2025
- Primary completion15 Jun 2028 (estimated)
- Study completion15 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Hypoxemic 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized Cross-over
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre for Medical Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Centre for Medical Sciences, Università degli Studi di Trento
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06921655
- Sponsor's protocol ID
- TEMA
- Acronym
- TEMA
- Status last verified
- Apr 2026
- First submitted
- 11 Mar 2025
- Last updated
- 5 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting prEssure-Muscle-index to Avoid Ventilatory Over-Assistance During Pressure
- ClinicalTrials.gov ID
- NCT06921655
- Acronym / sponsor ID
- TEMA / TEMA
- Keywords
- Pressure Support, Tidal Volume, Acute Hypoxemic Respiratory Failure
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Centre for Medical SciencesUniversity, hospital or other
- Study start
- 8 Oct 2025 (actual)
- Primary completion
- 15 Jun 2028 (estimated)
- Study completion
- 15 Dec 2028 (estimated)
- First posted
- 10 Apr 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.
The TEMA study (Targeting prEssure-Muscle-index to avoid ventilatory over-Assistance during pressure support ventilation) is a prospective, interventional crossover trial investigating the relationship between pressure support (PS) and tidal volume (Vt) in ICU patients with acute hypoxemic respiratory failure (AHRF) receiving pressure support ventilation (PSV). The study aims to assess whether the Pressure-Muscle Index (PMI)-a marker derived from the difference between plateau and peak inspiratory pressure-can help identify the optimal level of ventilatory assistance, preventing over-assistance and its associated complications such as diaphragm atrophy and patient self-inflicted lung injury (P-SILI). By exploring the sigmoidal relationship between PS and Vt, the study seeks to define a physiological threshold (PMI=0) that may serve as a personalized target for PSV titration.
Detailed description
The TEMA study is a prospective, interventional crossover trial designed to explore the physiological relationship between levels of pressure support (PS) and tidal volume (Vt) in mechanically ventilated ICU patients diagnosed with acute hypoxemic respiratory failure (AHRF). The goal is to identify a pressure support threshold beyond which over-assistance occurs, leading to excessive tidal volumes and suppression of respiratory muscle activity.
The central hypothesis is that the PS-Vt curve follows a sigmoidal pattern: an initial plateau phase with stable Vt is followed by a steep, compliance-driven increase in Vt at higher PS levels. The Pressure-Muscle Index (PMI), calculated as the difference between plateau pressure (Pplat) and peak airway pressure (Ppeak) during an inspiratory occlusion, is used to define this inflection point (PMI=0), which marks the transition from physiologically appropriate to excessive assistance.
Study Design: The study is conducted at the ICU of Santa Chiara Hospital (Trento, Italy) and includes seven levels of pressure support modulation-three above and three below the identified PMI=0 point. At each level, key physiological variables such as Vt, respiratory rate (RR), minute ventilation, PMI, and patient-ventilator asynchrony index are recorded.
A second evaluation between days 4-6 post-enrollment is planned for patients who remain intubated, to assess whether the PS-Vt relationship evolves over time, reflecting changes in respiratory drive and mechanics during the ICU course.
Technical Aspects:
Measurements include respiratory system compliance, work of breathing (WOB), inspiratory effort, and occlusion-based indices.
PS levels are applied in randomized order to minimize bias. Clinical PSV settings are reinstated between steps to avoid carryover effects and ensure patient safety.
Analytical Approach: The primary outcome is to characterize the PS-Vt relationship and validate the use of PMI as a physiological marker of the optimal support threshold. Nonlinear regression models, including sigmoidal curve fitting, will be used to identify inflection points (c parameters) in the PS-Vt curve. A Monte Carlo simulation informed the sample size, targeting 36 patients to account for potential dropouts, ensuring >90% power to detect a meaningful breakpoint.
Multivariable models will adjust for potential confounders such as PaCO₂, sedation depth, BMI, and baseline compliance.
Expected Impact: If successful, the TEMA study will provide a new physiologically grounded framework for tailoring pressure support in assisted ventilation. By validating PMI as a real-time bedside tool, the study may support a more personalized approach to weaning and ventilation management, potentially improving outcomes such as duration of ventilation, weaning success, and ICU stay.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 7
- Model description
- Randomized Cross-over
| Arm | Type | Receives |
|---|---|---|
| Pressure Support PMI=0 | Experimental | Procedure: Variation of Pressure Support LevelsThe PS level at which PMI is zeroed, meaning the patient's inspiratory effort contributes minimally to tidal volume |
| Pressure Support +2 | Experimental | Procedure: Variation of Pressure Support LevelsAbove PSPMI=0: +2 cmH₂O above PSPMI=0 (over-assistance zone). |
| Pressure Support +4 | Experimental | Procedure: Variation of Pressure Support LevelsAbove PSPMI=0: +4 cmH₂O above PSPMI=0 (over-assistance zone). |
| Pressure Support +6 | Experimental | Procedure: Variation of Pressure Support LevelsAbove PSPMI=0: +6 cmH₂O above PSPMI=0 (over-assistance zone). |
| Pressure Support -2 | Experimental | Procedure: Variation of Pressure Support LevelsBelow PSPMI=0: -2 cmH₂O below PSPMI=0 (under-assistance zone). |
| Pressure Support -4 | Experimental | Procedure: Variation of Pressure Support Levels- Below PSPMI=0: -4 cmH₂O below PSPMI=0 (under-assistance zone). |
| Pressure Support -6 | Experimental | Procedure: Variation of Pressure Support Levels- Below PSPMI=0: -6 cmH₂O below PSPMI=0 (under-assistance zone). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age ≥ 18 years
- Mechanically ventilated in the ICU
- Diagnosis of Acute Hypoxemic Respiratory Failure (AHRF)
- Normocapnia or non-severe hypercapnia
- Receiving Pressure Support Ventilation (PSV) for at least 24-72 hours
Key exclusion criteria (4 listed)
- Age < 18 years
- Known neurological or neuromuscular disorders affecting diaphragm function
- Chronic Obstructive Pulmonary Disease (COPD) or hypercapnic respiratory failure
- Psychomotor agitation or inadequate sedation
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 |
|---|---|---|
| Variation of Pressure Support LevelsPatients will undergo six randomized PS levels (+2, +4, +6 cmH₂O above and -2, -4, -6 cmH₂O below PSPMI=0). | Procedure or surgery | Pressure Support +2, Pressure Support +4, Pressure Support +6, Pressure Support -2, Pressure Support -4, Pressure Support -6, Pressure Support PMI=0 |
Primary outcome
Pressure Support-Tidal Volume (PS-Vt) Relationship
Time frame: Up to 5 minutes after each PS level adjustment during the interventional phase (Day 1)
The primary aim is to determine whether the PS-Vt curve exhibits a flat region (where tidal volume remains stable) before transitioning into a steep, compliance-dependent increase at higher PS levels. This transition point, identified as PSPMI=0, is hypothesized to represent the threshold for over-assistance.
11 secondary outcomes
Validation of Pressure-Muscle Index (PMI) as an Over-Assistance Marker
Time frame: Up to 5 minutes after each PS level adjustment during the interventional phase (Day 1) and during follow-up assessment on Days 4-6 (if patient remains intubated)
Impact of Respiratory Mechanics on PS-Vt Relationship
Time frame: During the interventional phase on Day 1 and during follow-up assessment on Days 4-6 (if patient remains intubated)
Rate of Ineffective Efforts During Over-Assistance
Time frame: Up to 5 minutes after each PS level adjustment during the interventional phase (Day 1) and during follow-up assessment on Days 4-6 (if patient remains intubated)
Effect of Over-Assistance on Ventilatory Asynchronies
Time frame: Up to 5 minutes after each PS level adjustment during the interventional phase (Day 1) and during follow-up assessment on Days 4-6 (if patient remains intubated)
Weaning failure
Time frame: Up to 100 months or until the of death from any cause, whichever came first.
Duration of mechanical ventilation
Time frame: From date of randomization until the date of extubation or date of death from any cause, whichever came first, assessed up to 100 months
ICU length of stay (LOS)
Time frame: Up to 100 months or until the of death from any cause, whichever came first.
Hospital length of stay (LOS)
Time frame: Up to 100 months or until the of death from any cause, whichever came first.
Impact of Respiratory Mechanics on PS-Vt Relationship
Time frame: From the randomization to 5 minutes.
Impact of Respiratory Mechanics on PS-Vt Relationship
Time frame: From the randomization to 5 minutes.
Spontaneous breathing failure
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
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 5 Jun 2026.
- Individual participant dataSharing planned: Undecided
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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.
Santa Chiara Hospital, Trento, Trentino-Alto Adige, Italy
Trento, Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Variation of Pressure Support Levels in people with Acute Hypoxemic Respiratory Failure and Mechanical Ventilation Complication, run by Centre for Medical Sciences 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 6 inclusion and 4 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: looking for participants now, as of the sponsor's last update on 5 Jun 2026. 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?
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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pressure Support-Tidal Volume (PS-Vt) Relationship (time frame: Up to 5 minutes after each PS level adjustment during the interventional phase (Day 1)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Jun 2026.