Progressive Pressure Support Reduction as Inspiratory Muscle Endurance Training in Mechanically Ventilated Patients (inspira-rct)

Progressive Pressure Support Reduction as Inspiratory Muscle Endurance Training in Mechanically Ventilated Critically Ill Patients: Effect on Maximal Inspiratory Pressure, Diaphragm Thickening Fraction, Weaning Success and Extubation (INSPIRA-RCT)

Mechanical ventilation causes rapid diaphragm muscle atrophy, detectable within 18 hours of ventilator support, which is a major contributor to weaning failure and prolonged ICU stay.

This randomized controlled trial tests whether a physiotherapist-guided inspiratory endurance training program - achieved by progressively reducing pressure support (PS) levels on the ventilator - can preserve or improve inspiratory muscle strength and diaphragm structure in critically ill adults on mechanical ventilation, compared to standard ICU care.

Participants will be randomly assigned to one of two groups. The intervention group will receive twice-daily training sessions (weekdays only) in which the physiotherapist gradually reduces PS by up to 50% of the baseline level, causing the patient to breathe with greater muscular effort - equivalent to progressive endurance exercise for the diaphragm. The control group will receive standard weaning care as directed by the attending intensivist.

The primary outcome is maximal inspiratory pressure (PImax) at day 7. Secondary outcomes include diaphragm thickening fraction measured by ultrasound, time to successful extubation, weaning success rate, and mortality.

All measurements are performed by the ICU physician (blinded to group allocation) using airway occlusion maneuvers recorded on the ventilator and diaphragm ultrasound, following a standardized protocol.

Study Overview

• Status: Not yet recruiting
• Conditions: Physiotherapy; Respiratory Muscle Weakness; Endurance Training; Mechanical Ventilation Weaning
• Intervention / Treatment: Behavioral: Progressive Pressure Support Reduction (IRT-PS); Other: Standard ICU Care

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ricardo Miguel Rodrigues-Gomes; Phone Number: +34618060702; Email: ric.mr.gomes@gmail.com

Study Locations

• Spain
  • Vigo, Spain
    • Hospital Álvaro Cunqueiro
    • Contact: Ricardo Miguel Rodrigues-Gomes, PhD; Phone Number: +34618060702; Email: ric.mr.gomes@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. Admitted to ICU with invasive mechanical ventilation for more than 48 hours at the time of randomization
3. Expected to remain intubated for at least 24 additional hours, at the discretion of the attending intensivist
4. Active pressure support ventilation (PSV) mode with PS level ≥ 5 cmH2O
5. Richmond Agitation-Sedation Scale (RASS) score between -1 and +1
6. Arterial pH ≥ 7.35 and serum lactate ≤ 2.0 mmol/L
7. Peripheral oxygen saturation (SpO2) ≥ 90% with current FiO2
8. Informed consent obtained from patient or legal representative

Exclusion Criteria:

1. Neurological condition affecting central respiratory control (high cervical spinal cord injury, ALS, myasthenia gravis, active Guillain-Barré syndrome)
2. Established tracheostomy at the time of inclusion
3. Restriction on head-of-bed elevation to ≥ 30 degrees
4. Decision to limit therapeutic effort (LET) or life expectancy < 48 hours
5. Active hemodynamic instability (requirement for ≥ 2 vasopressors or vasopressor adjustment within the last 6 hours)
6. Multiple rib fractures or undrained pneumothorax
7. Simultaneous participation in another interventional clinical trial
8. Previous inclusion in this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inspiratory Resistance Training (IRT-PS); Physiotherapist-guided inspiratory endurance training by progressive pressure support reduction (25-50% of baseline PS), 1-3 sets of 5-15 minutes, twice daily on weekdays, for up to 14 days or until extubation. Target: Borg CR10 score 3-5. P0.1 monitored continuously; sessions stopped if P0.1 > 4 cmH2O sustained > 2 minutes.	Behavioral: Progressive Pressure Support Reduction (IRT-PS); Progressive reduction of pressure support (PS) during ventilator-assisted breathing, performed by a physiotherapist twice daily (weekdays only). Sessions consist of 1-3 sets of 5-15 minutes with 2-minute rest intervals at baseline PS. PS is reduced by 25% initially up to a maximum of 50% of baseline (minimum 5 cmH2O) for PS ≥10 cmH2O; by 1-2 cmH2O for PS 5-9 cmH2O; and by 1 cmH2O down to 0 cmH2O for PS <5 cmH2O. Target perceived exertion: Borg CR10 3-5. P0.1 monitored continuously; session stopped if P0.1 >4 cmH2O sustained >2 minutes (Goligher et al. criteria). Safety stop criteria: RR >35 rpm, SpO2 <90%, HR >120 bpm.
Active Comparator: Standard Care (Usual Care); Conventional weaning as directed by the attending intensivist, without a structured inspiratory muscle training program. Conventional physiotherapy (early mobilization, chest physiotherapy) is permitted in both groups.	Other: Standard ICU Care; Conventional weaning managed by the attending intensivist according to standard clinical practice, without a structured inspiratory muscle training protocol. Conventional physiotherapy (early mobilization, chest physiotherapy) permitted in both groups.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal Inspiratory Pressure (PImax)	Measured by manual airway occlusion at end-expiration with pressure curve recorded on the ventilator. Standardized verbal instruction given to the patient. Best of 3 valid maneuvers recorded. Performed by the ICU physician blinded to group allocation.	Day 7 from randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diaphragm Thickening Fraction (DTF)	measured by ultrasound (linear probe 7-15 MHz, zone of apposition, M-mode, average of 3 cycles). Performed by ICU physician per standardized protocol.	Days 0, 3, 7 and 14 from randomization
P0.1 (Airway Occlusion Pressure at 100ms	respiratory drive indicator, read directly from ventilator display	Baseline and days 3, 7 and 14; and at start, mid and end of each training session (intervention group)
Time to Successful Extubation	hours from randomization to extubation without reintubation within 48 hours	From randomization until extubation, up to 14 days
Weaning Success Rate	proportion of patients extubated without reintubation within 48 hours	Days 7 and 14 from randomization
Sustained Pressure Support Reduction	difference in cmH2O between baseline PS at Day 0 and Day 7	days 1, 3, 5 and 7 from randomization
Total Days on Mechanical Ventilation		From randomization until ICU discharge, up to 30 days
ICU Mortality		At the time of ICU discharge (up to 24 weeks)
30-day Mortality		Day 30 from randomization
ICU Readmission at 30 days		Day 30 from randomization
Borg CR10 Score during training session	perceived respiratory exertion (0-10)	Periprocedural (from the start of the session until 30 minutes post-intervention)
Adverse events during training sessions	episodes of RR >35, SpO2 <90%, HR >120 bpm	Periprocedural (from the start of the session until 30 minutes post-intervention)

Collaborators and Investigators

• Sponsor: University of Santiago de Compostela

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): March 30, 2028

Study Registration Dates

• First Submitted: May 23, 2026
• First Submitted That Met QC Criteria: July 4, 2026
• First Posted (Actual): July 8, 2026

Study Record Updates

• Last Update Posted (Actual): July 8, 2026
• Last Update Submitted That Met QC Criteria: July 4, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: INSPIRA-RCT-2026-HACunqueiro

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No