Clinical trial NCT06921655: Targeting prEssure-Muscle-index to Avoid Ventilatory Over-Assistance During Pressure Support Ventilation
Official title: Targeting prEssure-Muscle-index to Avoid Ventilatory Over-Assistance During Pressure
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Acute Hypoxemic Respiratory Failure
Mechanical Ventilation Complication
Keywords: Pressure Support
Tidal Volume
Acute Hypoxemic Respiratory Failure
Lead sponsor: Università degli Studi di Trento
Sponsor class: OTHER
First posted: 2025-04-10
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized Cross-over
Primary purpose: TREATMENT

Brief 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) 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.

Eligibility criteria: 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

Primary outcomes:
measure: Pressure Support-Tidal Volume (PS-Vt) Relationship
timeFrame: Up to 5 minutes after each PS level adjustment during the interventional phase (Day 1)
Secondary outcomes:
measure: Validation of Pressure-Muscle Index (PMI) as an Over-Assistance Marker
timeFrame: 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)
measure: Impact of Respiratory Mechanics on PS-Vt Relationship
timeFrame: During the interventional phase on Day 1 and during follow-up assessment on Days 4-6 (if patient remains intubated)
measure: Rate of Ineffective Efforts During Over-Assistance
timeFrame: 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)
measure: Effect of Over-Assistance on Ventilatory Asynchronies
timeFrame: 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)
measure: Weaning failure
timeFrame: Up to 100 months or until the of death from any cause, whichever came first.
measure: Duration of mechanical ventilation
timeFrame: From date of randomization until the date of extubation or date of death from any cause, whichever came first, assessed up to 100 months
measure: ICU length of stay (LOS)
timeFrame: Up to 100 months or until the of death from any cause, whichever came first.
measure: Hospital length of stay (LOS)
timeFrame: Up to 100 months or until the of death from any cause, whichever came first.
measure: Impact of Respiratory Mechanics on PS-Vt Relationship
timeFrame: From the randomization to 5 minutes.
measure: Impact of Respiratory Mechanics on PS-Vt Relationship
timeFrame: From the randomization to 5 minutes.
measure: Spontaneous breathing failure
timeFrame: 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
Other outcomes:
Locations:
city: Trento
country: Italy
facility: Centre for Medical Sciences
Study officials:
References: