Targeting prEssure-Muscle-index to Avoid Ventilatory Over-Assistance During Pressure Support Ventilation (TEMA)

January 30, 2026 updated by: Centre for Medical Sciences

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

36

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Trento
      • Trento, Trento, Italy, 38122

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Mechanically ventilated in the ICU
  3. Diagnosis of Acute Hypoxemic Respiratory Failure (AHRF)
  4. Normocapnia or non-severe hypercapnia
  5. Receiving Pressure Support Ventilation (PSV) for at least 24-72 hours
  6. Presence of an arterial line for blood gas sampling

Exclusion Criteria:

  1. Age < 18 years
  2. Known neurological or neuromuscular disorders affecting diaphragm function
  3. Chronic Obstructive Pulmonary Disease (COPD) or hypercapnic respiratory failure
  4. Psychomotor agitation or inadequate sedation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pressure Support PMI=0
The PS level at which PMI is zeroed, meaning the patient's inspiratory effort contributes minimally to tidal volume
Procedure: Variation of Pressure Support Levels
Patients will undergo six randomized PS levels (+2, +4, +6 cmH₂O above and -2, -4, -6 cmH₂O below PSPMI=0).
Experimental: Pressure Support +2
Above PSPMI=0: +2 cmH₂O above PSPMI=0 (over-assistance zone).
Procedure: Variation of Pressure Support Levels
Patients will undergo six randomized PS levels (+2, +4, +6 cmH₂O above and -2, -4, -6 cmH₂O below PSPMI=0).
Experimental: Pressure Support +4
Above PSPMI=0: +4 cmH₂O above PSPMI=0 (over-assistance zone).
Procedure: Variation of Pressure Support Levels
Patients will undergo six randomized PS levels (+2, +4, +6 cmH₂O above and -2, -4, -6 cmH₂O below PSPMI=0).
Experimental: Pressure Support +6
Above PSPMI=0: +6 cmH₂O above PSPMI=0 (over-assistance zone).
Procedure: Variation of Pressure Support Levels
Patients will undergo six randomized PS levels (+2, +4, +6 cmH₂O above and -2, -4, -6 cmH₂O below PSPMI=0).
Experimental: Pressure Support -2
Below PSPMI=0: -2 cmH₂O below PSPMI=0 (under-assistance zone).
Procedure: Variation of Pressure Support Levels
Patients will undergo six randomized PS levels (+2, +4, +6 cmH₂O above and -2, -4, -6 cmH₂O below PSPMI=0).
Experimental: Pressure Support -4
- Below PSPMI=0: -4 cmH₂O below PSPMI=0 (under-assistance zone).
Procedure: Variation of Pressure Support Levels
Patients will undergo six randomized PS levels (+2, +4, +6 cmH₂O above and -2, -4, -6 cmH₂O below PSPMI=0).
Experimental: Pressure Support -6
- Below PSPMI=0: -6 cmH₂O below PSPMI=0 (under-assistance zone).
Procedure: Variation of Pressure Support Levels
Patients will undergo six randomized PS levels (+2, +4, +6 cmH₂O above and -2, -4, -6 cmH₂O below PSPMI=0).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 5 minutes after each PS level adjustment during the interventional phase (Day 1)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
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.
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)
Evaluation of how respiratory compliance (Crs) influence the PS-Vt curve. The study will investigate individual variations in ventilatory response to PS.
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)
Quantification of ineffective respiratory efforts (i.e., inspiratory efforts not followed by ventilator-triggered breaths) during PS levels exceeding the identified PSPMI=0 threshold.
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.
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.
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
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.
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.
Total duration (in days) of ICU admission, analyzing whether PSV settings influence prolonged ICU stays due to delayed weaning, respiratory complications, or ventilatory asynchronies
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.
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.
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.
Evaluation of how respiratory drive influence the PS-Vt curve. The study will investigate individual variations in ventilatory response to PS.
From the randomization to 5 minutes.
Impact of Respiratory Mechanics on PS-Vt Relationship
Time Frame: From the randomization to 5 minutes.
Evaluation of how patient effort (Pmus) influence the PS-Vt curve. The study will investigate individual variations in ventilatory response to PS.
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
Defined as the Number of Participants who fail transition from PCV to PSV.
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
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)
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.
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre for Medical Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 8, 2025

Primary Completion (Estimated)

April 8, 2027

Study Completion (Estimated)

April 8, 2027

Study Registration Dates

First Submitted

March 11, 2025

First Submitted That Met QC Criteria

April 2, 2025

First Posted (Actual)

April 10, 2025

Study Record Updates

Last Update Posted (Actual)

February 3, 2026

Last Update Submitted That Met QC Criteria

January 30, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TEMA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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