Clinical trial NCT01193816: Loxapine in the Management of Restlessness During Mechanical Ventilation Weaning
Official title: Assessment of Loxapine in the Management of Restlessness During Mechanical Ventilation Weaning
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Restlessness
Keywords: restlessness during mechanical ventilation weaning
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2010-09-02
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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

Primary outcomes:
measure: Weaning period
timeFrame: up to 28 days
Secondary outcomes:
measure: total duration of mechanical ventilation
timeFrame: up to 28 days
measure: incidence of unexpected extubations
timeFrame: up to 28 days
measure: clinical and biological respiratory parameters
timeFrame: 24 hours
measure: incidence of mechanical ventilation related complications
timeFrame: up to 48 hours after extubation
measure: incidence of adverse events, related and non related to the treatment
timeFrame: up to 28 days
measure: mortality rate
timeFrame: day 14 and week 6
measure: factors associated to weaning failure
timeFrame: up to 28 days
Other outcomes:
Locations:
city: Colombes
country: France
facility: Hôpital Louis Mourier
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Didier Dreyfuss, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gaudry S, Sztrymf B, Sonneville R, Megarbane B, Van Der Meersch G, Vodovar D, Cohen Y, Ricard JD, Hajage D, Salomon L, Dreyfuss D. Loxapine to control agitation during weaning from mechanical ventilation. Crit Care. 2017 Sep 6;21(1):235. doi: 10.1186/s13054-017-1822-y.