PERMISSive Lung-protective Ventilation RCT

NCT07837128 | Recruiting DMC

• 3 other identifiers: NL-01197610390042410066NL-OMON61463
• Study Type: interventional
• Target: 926
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to investigate the impact of a ventilation strategy with a lower respiratory rate (RR) (permissive lung-protective ventilation) on clinical outcomes in adult critically ill patients receiving invasive ventilation. The main question it aims to answer is: Is a permissive lung-protective ventilation, defined as a strategy that reduces ventilatory intensity by stepwise lowering RR to the lowest level permitted by predefined safety limits, superior to conventional lung-protective ventilation, with respect to the number of days free from ventilation and alive at day 28 (VFD-28) in adult critically ill patients receiving invasive ventilation? Researchers will compare permissive lung-protective ventilation with conventional lung-protective ventilation to see if it improves clinical outcomes. Participants will be randomly assigned to one of the two ventilation strategies under investigation and followed up for 28 days.

Conditions

Invasive Ventilation; Critical Illness; Intensive Care (ICU); Mechanical Ventilation

Keywords

Intensive Care; Mechanical Ventilation; respiratory rate; mechanical power

Outcome Measures

Primary Outcomes (1)

• Number of days free from ventilation and alive at day 28 (VFD-28)

  Ventilator-free days at day 28 (VFD-28) is defined as: * VFD-28 = 0 if a subject dies within 28 days of start of invasive ventilation; * VFD-28 = 0 if a subject is invasively ventilated for ≥28 days; * VFD-28 = 28 - X days after tracheal intubation if a subject is successfully liberated from ventilation.

  From start of invasive ventilation to successful liberation from ventilation, death or day 28, whichever occurs first

Secondary Outcomes (12)

• Duration of ventilation

  From start of invasive ventilation to successful liberation from ventilation, death or day 28, whichever occurs first.

• 28-day mortality

  from randomization to day 28

• Intensive Care Unit (ICU) length of stay

  from randomization to ICU discharge, death or day 90, whichever occurs first.

• Hospital length of stay

  from randomization to hospital discharge, death or day 90, whichever occurs first.

• Successful switch to pressure support ventilation

  from start of invasive ventilation to successful liberation from ventilation, death or day 28, whichever occurs first.

Study Arms (2)

Permissive lung-protective ventilation

EXPERIMENTAL

The goal is to achieve the lowest possible respiratory rate (RR) according to a guideline.

Other: Permissive lung-protective ventilation

Conventional lung-protective ventilation

ACTIVE COMPARATOR

The respiratory rate is set according to standard of care.

Other: Conventional lung-protective ventilation

Interventions

Permissive lung-protective ventilation OTHER

The goal is to achieve the lowest possible respiratory rate (RR) guided by a nomogram, that integrates baseline RR with arterial blood gas analysis (ABG) results, to stay within safety limits of PaCO2 and pH. The lowest RR possible is determined by the maximum acceptable PaCO2 of ≤ 8.5 kPa (64 mmHg) and limited by the lowest acceptable pH of \> 7.20, depending on the combination. The nomogram provides guidance on RR reductions based on these safety limits. The first target RR is determined using the baseline RR and the first ABG, obtained within 1 hour after randomization. The set RR is gradually decreased in steps of 2 breaths, approximately every 10 to 20 minutes, and downtitration is intended to be completed between 4 to 6 hours. Other ventilator settings are set according to lung-protective ventilation, following international guidelines.

Permissive lung-protective ventilation

Conventional lung-protective ventilation OTHER

The respiratory rate (RR) is set according to standard of care, starting to target a normal PaCO2 (4.7-6.4 kPa or 35-48 mmHg) and/or a normal arterial pH (7.35-7.45). Other ventilator settings according to lung-protective ventilation, following international guidelines.

Conventional lung-protective ventilation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• admission to one of the participating intensive care units (ICUs);
• intubated and receiving invasive ventilation; and
• expected duration of ventilation of at least 24 hours (based on ICU admission diagnosis and clinical judgment).

You may not qualify if:

• age below 18 years;
• invasive ventilation before randomization \> 2 hours in the ICU or invasive ventilation \> 6 hours in the operating room or emergency department directly preceding the current ICU admission;
• receiving or planned to receive veno-venous, veno-arterial or arterio-venous extracorporeal membrane oxygenation (ECMO);
• contraindications for hypercapnia, such as ongoing cardiac ischemia (as defined in the guideline of the European Society of Cardiology), or having suspected or confirmed increased intracranial pressure due to (traumatic) brain injury, judged by the attending physician;
• having severe Chronic Obstructive Pulmonary Disease (COPD); GOLD classification III or IV or classified in group B or E of the GOLD ABE assessment tool);
• after cardiac arrest;
• suspected or confirmed pregnancy;
• having any neurologic diagnosis that can prolong duration of mechanical ventilation, e.g., Guillain-Barré syndrome, high spinal cord lesion or amyotrophic lateral sclerosis, multiple sclerosis, or myasthenia gravis;
• participation in another interventional trial using similar endpoints;
• previous randomization in this study;
• no informed consent or;
• admitted for palliative and terminal care.

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (2)

Amsterdam UMC, locatie AMC

Amsterdam, NL, 1100 DD, Netherlands

NOT YET RECRUITING

Reinier De Graaf

Delft, NL, 2625 AD, Netherlands

RECRUITING

MeSH Terms

Conditions

Critical Illness

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Frederique Paulus, Full Professor

  Amsterdam AMC, Amsterdam, the Netherlands

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laura A. Buiteman-Kruizinga, PhD

CONTACT

+31627153843; l.a.kruizinga@amsterdamumc.nl

Amarens Hoogenboom, MD

CONTACT

+31615147102; h.b.a.hoogenboom@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Outcome measures will be collected by an investigator blinded to the randomized treatment allocation. All analyses are preplanned, i.e., before closing of the database, and will be performed by an investigator that remains blinded for treatment allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: International, multicenter, investigator-initiated, parallel, superiority randomized clinical trial

Study Record Dates

• First Submitted: September 16, 2026
• First Posted: September 23, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: September 23, 2026

Record last verified: 2026-09

Locations

NL (2)