PERMISSive Lung-protective Ventilation in Critically Ill Invasively Ventilated Patients (PERMISS) - a Randomized Clinical Trial
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 926
- Locations
- 2
- Primary Endpoint
- Number of days free from ventilation and alive at day 28 (VFD-28)
Study Overview
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.
Detailed Description
RATIONALE Injury caused by mechanical ventilation is associated with its intensity, of which the respiratory rate (RR) is a substantial contributor. A permissive ventilation strategy that reduces RR and allows mild hypercapnia, may lower the intensity of ventilation and improve patient-centered outcomes. In this approach, RR is stepwise decreased to the lowest level compatible with predefined safety limits.
OBJECTIVE To compare permissive lung-protective ventilation with a lower RR, to conventional lung-protective ventilation, in adult critically ill patients receiving invasive ventilation.
HYPOTHESIS 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, is 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.
STUDY DESIGN International, multicenter, investigator-initiated, randomized, clinical, superiority trial.
STUDY POPULATION Critically ill patients, aged ≥ 18 years, intubated and expected to receive invasive ventilation for > 24 hours.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Masking Description
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.
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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).
Exclusion Criteria
- •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.
Arms & Interventions
Conventional lung-protective ventilation
The respiratory rate is set according to standard of care.
Intervention: Conventional lung-protective ventilation (Other)
Permissive lung-protective ventilation
The goal is to achieve the lowest possible respiratory rate (RR) according to a guideline.
Intervention: Permissive lung-protective ventilation (Other)
Outcomes
Primary Outcomes
Number of days free from ventilation and alive at day 28 (VFD-28)
Time Frame: From start of invasive ventilation to successful liberation from ventilation, death or day 28, whichever occurs first
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.
Secondary Outcomes
- Intensive Care Unit (ICU) mortality(from randomization to day 90)
- 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.)
- Hospital mortality(from randomization to day 90)
- Incidence of Acute Respiratory Distress Syndrome (ARDS)(from randomization to day 28)
- Incidence of Acute Kidney Injury (AKI)(from randomization to day 28)
- Incidence of severe hypercapnia(from randomization to end of the intervention)
- Incidence of severe hypoxemia(from randomization to end of the intervention)
- Incidence of ventilation-associated complications(from randomization to end of the intervention)
Investigators
Laura Buiteman-Kruizinga
Principal Investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)