Loxapine in the Management of Restlessness During Mechanical Ventilation Weaning (Sevralox)

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

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.

Study Overview

• Status: Completed
• Conditions: Restlessness
• Intervention / Treatment: Drug: Placebo; Drug: loxapine

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 Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Colombes, France
    • Hopital Louis Mourier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo
Experimental: loxapine	Drug: loxapine; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: August 26, 2010
• First Submitted That Met QC Criteria: September 1, 2010
• First Posted (Estimate): September 2, 2010

Study Record Updates

• Last Update Posted (Estimate): July 18, 2014
• Last Update Submitted That Met QC Criteria: July 17, 2014
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: restlessness during mechanical ventilation weaning
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Dyskinesias; Psychomotor Disorders; Psychomotor Agitation; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Dopamine Agents; Dopamine Antagonists; Loxapine
• Other Study ID Numbers: P 070106