Prolonged weaning from invasive mechanical ventilation is a major challenge in critically ill patients failing a spontaneous breathing trial. Levosimendan, a calcium sensitiser, has been shown to improve respiratory muscle function. However, its effect on clinically relevant endpoints in difficult to wean patients has not yet been investigated. We aim to assess whether levosimendan shortens the weaning process in invasively ventilated intensive care unit (ICU) patients who fail a separation attempt. The objective is to assess the effect of levosimendan on the number of ventilator-free days and alive at day 28.

The WEANing with LEvoSimendan Study (WEANLESS) is an investigator-initiated, multicentre, double-blind, parallel-group, randomised clinical superiority trial. Adult invasively ventilated patients who failed a separation attempt are randomly assigned to receive either intravenous levosimendan (intervention) or placebo (control). The primary outcome is the number of ventilator-free days and alive at day 28 from randomisation. WEANLESS also evaluates the effects of levosimendan on patient-reported outcomes, measured through daily dyspnoea scores and uses an EQ-5D-5L questionnaire. Additionally, we will evaluate healthcare resource utilisation and intensive care capacity, assessed through reintubation rates, ICU readmissions within 90 days, the need for non-invasive respiratory support and ICU length of stay. WEANLESS includes a pharmacokinetic analysis of levosimendan and its metabolites.

WEANLESS is the first clinical study that is sufficiently powered to determine the effect of intravenous levosimendan in difficult to wean patients on the duration of weaning from invasive ventilation.

WEANLESS is registered before the inclusion of the first patient at clinicaltrials.gov; the study protocol has been approved by the relevant ethics committee. Its findings will be disseminated through presentations at scientific conferences and publications in a peer-reviewed journal.

NCT07105202.

To identify and prioritise the most appropriate (de)prescribing interventions in inpatient and outpatient hospital care to advance environmentally sustainable healthcare.

A modified RAND Delphi study.

Inpatient and outpatient hospital care in the Netherlands.

The Delphi panel consisted of 63 participants, comprising 36 physicians and 27 pharmacists working in Dutch hospitals.

Consensus on the appropriateness of (de)prescribing interventions for frequently used medications in inpatient and outpatient hospital care to advance environmentally sustainable healthcare and the prioritisation of interventions per care setting (inpatient/outpatient) and intervention type (deprescribing/sustainable dosage form), culminating in a top 20.

51 (de)prescribing interventions were identified for 18 medication classes, for which consensus on appropriateness was reached for 42 (82%). The top 20 highest ranked interventions were identified, starting with switching from intravenous to oral administration of paracetamol, stopping chronically used proton pump inhibitors without indication and initiating antibiotics orally in case of good bioavailability.

Most (de)prescribing interventions were considered appropriate for advancing sustainable medication use, highlighting support for their potential implementation to reduce the environmental burden of healthcare.