Loxapine in the Management of Restlessness During Mechanical Ventilation Weaning

Phase 4

Completed

• Conditions: Restlessness
• Interventions: Drug: loxapine; Drug: Placebo

• Registration Number: NCT01193816
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Study Timeline

• Study First Submitted: 2010-08-26
• Study First Submitted QC: 2010-09-01
• Study First Posted: 2010-09-02
• Study Start: 2011-05
• Status Verified: 2012-07
• Primary Completion: 2014-05
• Study Completion: 2014-07
• Last Update Submitted: 2014-07-17
• Last Update Posted: 2014-07-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
loxapine	loxapine	loxapine
Placebo	Placebo	Placebo

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Hôpital Louis Mourier; 🇫🇷 Colombes, France