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

• ClinicalTrials.gov Identifier: NCT01193816
• Recruitment Status: Completed
• First Posted: September 2, 2010
• Last Update Posted: July 18, 2014
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Tracking Information

• First Submitted Date: August 26, 2010
• First Posted Date: September 2, 2010
• Last Update Posted Date: July 18, 2014
• Study Start Date: May 2011
• Actual Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 1, 2010)

Weaning period [ Time Frame: 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)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 25, 2012)

• total duration of mechanical ventilation [ Time Frame: up to 28 days ]
  -number of days of mechanical ventilation
• incidence of unexpected extubations [ Time Frame: up to 28 days ]
  number of patients with unexpected extubation
• clinical and biological respiratory parameters [ Time Frame: 24 hours ]
  description of abnormal clinical and biological respiratory parameters, number of patients concerned.
• incidence of mechanical ventilation related complications [ Time Frame: 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 [ Time Frame: up to 28 days ]
• mortality rate [ Time Frame: day 14 and week 6 ]
  mortality rate at day 14 and week 6
• factors associated to weaning failure [ Time Frame: up to 28 days ]
  age, patient medical history,duration of sedation or ventilation, weaning failure

Original Secondary Outcome Measures (submitted: September 1, 2010)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Loxapine in the Management of Restlessness During Mechanical Ventilation Weaning
• Official Title: Assessment of Loxapine in the Management of Restlessness During Mechanical Ventilation Weaning
• 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 Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Restlessness

Intervention

• 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.
• Drug: Placebo
  Placebo

Study Arms

• Experimental: loxapine
  loxapine
  Intervention: Drug: loxapine
• Placebo Comparator: Placebo
  Placebo
  Intervention: Drug: Placebo

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 17, 2014): 100
• Original Estimated Enrollment (submitted: September 1, 2010): 300
• Actual Study Completion Date: July 2014
• Actual Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT01193816
• Other Study ID Numbers: P 070106
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Assistance Publique - Hôpitaux de Paris
• Original Responsible Party: Saliha DJANE, Department Clinical Research of Developpement
• Current Study Sponsor: Assistance Publique - Hôpitaux de Paris
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Didier Dreyfuss, MD; Assistance Publique - Hôpitaux de Paris

• PRS Account: Assistance Publique - Hôpitaux de Paris
• Verification Date: July 2012