Effects of PERMISSive lung-protective ventilation on outcome in critically ill, invasively ventilated patients (PERMISS): protocol for a feasibility and safety randomised clinical trial.

INTRODUCTION: Mechanical power (MP) of ventilation is a summary variable of determinants of ventilator-induced lung injury and is consistently associated with worse outcomes. Lung-protective ventilation (LPV) using a lower respiratory rate (RR) is an appealing strategy to reduce MP, but it is unclear whether reducing RR is feasible and safe in critically ill patients under invasive mechanical ventilation. Therefore, we test the hypothesis that a ventilation strategy that targets the lowest acceptable RR is feasible and safe. METHODS AND ANALYSIS: The 'Effects of PERMISSive Lung-protective Ventilation on Outcome in Critically Ill, Invasively Ventilated Patients (PERMISS)' pilot study is an international, multicentre randomised clinical feasibility and safety trial in critically ill, invasively ventilated adult patients with an expected duration of ventilation >24 hours. Patients will be randomly assigned to 'permissive' LPV with a lower RR, within safety limits of arterial partial pressure of carbon dioxide (PaCO2) and pH, compared with conventional LPV with RR to target normal PaCO2 and pH. The primary endpoint is the difference in RR between the two groups from the start of ventilation until the first extubation. Secondary endpoints include safety, assessed by the incidence of unacceptable hypercapnia (PaCO2>70 mm Hg and pH<7.20), severe hypoxaemia (arterial partial pressure of oxygen (PaO2)<60 mm Hg), ventilator-associated complications and compliance with the protocol and quality of data collection. ETHICS AND DISSEMINATION: The current version of the protocol is V.3 (issued on 11 December 2025). The trial was approved by the medical research ethics committee of Leiden Den Haag Delft (approval number NL-009624.P25.028) on 2 June 2025, including all amendments, and was registered on www. CLINICALTRIALS: gov (NCT07077174). The PERMISS pilot is currently recruiting patients. TRIAL REGISTRATION NUMBER: NCT07077174.