Evaluation of the benefit of loxapine in controlling agitation during weaning from mechanical ventilation. Randomized, controlled trial - SEVRALOX

INTERVENTION: Trade Name: LOXAPAC Product Name: LOXAPAC Pharmaceutical Form: Oral solution INN or Proposed INN: Loxapine CAS Number: 1977-10-2 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 25 mg/ml Pharmaceutical form of the placebo: Oral solution Route of administration of the placebo: Parenteral use (Noncurrent) CONDITION: Agitation during weaning from mechanical ventilation; MedDRA version: 8.1 Level: PT Classification code 10067221 Term: Mechanical ventilation PRIMARY OUTCOME: Main Objective: To compare the time to successful extubation (extubation without the need for reintubation within 48 hours) between two groups of patients: those who received loxapine and those who received a placebo, in addition to their usual care. Primary end point(s): 1. Primary criterion: - the weaning time, defined as the time (expressed in days) between the first administration of the study product (or its placebo) and extubation, not followed by reintubation after 48 hours; 2. Secondary evaluation criteria: - the total duration of mechanical ventilation; - the rate of unplanned extubation; - clinical and blood gas parameters; - the rate of ventilator-associated complications; - the rate of occurrence of potentially treatment-related adverse events; - the mortality rate at day 14 and at 6 weeks; - investigation of factors associated with weaning failure; Secondary Objective: To compare between the two patient groups: - the total duration of mechanical ventilation; - the rate of unplanned extubation; - the evolution of clinical and blood gas parameters; - the rate of ventilator-associated complications; - the occurrence of possible side effects of the treatment; - the death rates at day 14 and at 6 weeks after inclusion; ; ; INCLUSION CRITERIA: - Age ≥ 18 years - Receiving sedation - On mechanical ventilation via an intubation tube (oro- or naso-)tracheal for more than 48 hours - Patient with no contraindication to a nasogastric tube - For whom potential weaning criteria from the ventilator are met - Affiliation to a social security scheme or CMU - Obtaining consent from family members or the person of trust if they are present. - Patients who experience marked agitation upon complete (or near-complete) cessation of sedation, without potential danger to the patient, but leading to the reintroduction of sedation with opioids and benzodiazepines at doses incompatible with continued withdrawal. This state of agitation is defined by a RASS (Richmond Agitation-Sedation Scale) score of 2. Are the trial subjects under 18? No.