Loxapine in the Management of Restlessness During Mechanical Ventilation Weaning

Condition(s) targeted: Restlessness

Intervention: loxapine (Drug); Placebo (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Assistance Publique - Hôpitaux de Paris

Official(s) and/or principal investigator(s):
Didier Dreyfuss, MD, Principal Investigator, Affiliation: Assistance Publique - Hôpitaux de Paris

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.

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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Weaning period

Secondary outcome:

total duration of mechanical ventilation

incidence of unexpected extubations

clinical and biological respiratory parameters

incidence of mechanical ventilation related complications

incidence of adverse events, related and non related to the treatment

mortality rate

factors associated to weaning failure

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Hôpital Louis Mourier, Colombes, France

Starting date: May 2011
Last updated: July 17, 2014