Loxapine in the Management of Restlessness During Mechanical Ventilation Weaning

Study Overview
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Brief Summary
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This study aims to assess the efficacy of a drug (loxapine, a neuroleptic) in calming patients down in a situation of restlessness during mechanical ventilation weaning. This drug is used for several years to quieten restless patients. Its purpose is to restore spontaneous breathing sooner and therefore to reduce the risks of intubation and mechanical ventilation.

Detailed Description
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This study aims to assess the efficacy of a drug (loxapine, a neuroleptic) in calming patients down in a situation of restlessness during mechanical ventilation weaning. This drug is used for several years to quieten restless patients. Its purpose is to restore spontaneous breathing sooner and therefore to reduce the risks of intubation and mechanical ventilation. 300 patients will participate in the study and will be randomized, after informed consent, to receive either loxapine or a placebo.Patients whose proxies refuse participation will be sedated according to standard care procedures.

Official Title
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Assessment of Loxapine in the Management of Restlessness During Mechanical Ventilation Weaning

Conditions
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Restlessness

Intervention / Treatment
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* Drug: loxapine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ≥ 18 years, sedated under mechanical ventilation through intubation probe for more than 48 hours no contra-indication to naso-gastric probe- with criteria for potential weaning with social security important restlessness at sedation withdrawal, defined as RASS score (Richmond Agitation Sedation Scale)= 2. This restlessness has no potential danger for the patient but requires a level of sedation. This re-sedation implies administration of morphinomimetics and benzodiazepines at dosages that does not allow to pursue mechanical ventilation weaning attempts. Exclusion Criteria: extreme restlessness at sedation withdrawal ((RASS>2) allergy to loxapine or one of its component dopaminergic agonists extubation planned in the following 24 hours antecedent of comitiality known pregnancy at admission proxies opposed to study participation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: loxapine<br>loxapine | Drug: loxapine<br>* Each patient may receive a maximum dosage of 900mg of Loxapine per day (drinkable solution through gastric probe) or the same volume of placebo. 2 initial administrations of 150 mg followed by potential readministration of 100 mg of loxapine. Maximum duration of treatment will be 14 days.The dosage by day is defined by patients' clinical condition, assessed with RASS score.<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weaning period | Weaning period (days) between inclusion (ie first administration of loxapine/placebo) and successful extubation (no re-intubation in the following 48 hours) | up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| total duration of mechanical ventilation | -number of days of mechanical ventilation | up to 28 days | 
| incidence of unexpected extubations | number of patients with unexpected extubation | up to 28 days | 
| clinical and biological respiratory parameters | description of abnormal clinical and biological respiratory parameters, number of patients concerned. | 24 hours | 
| incidence of mechanical ventilation related complications | collapses, nosocomial pneumonia, respiratory issue requiring an increase of FiO2 and/or PEP. | up to 48 hours after extubation | 
| incidence of adverse events, related and non related to the treatment |  | up to 28 days | 
| mortality rate | mortality rate at day 14 and week 6 | day 14 and week 6 | 
| factors associated to weaning failure | age, patient medical history,duration of sedation or ventilation, weaning failure | up to 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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restlessness during mechanical ventilation weaning