Evaluating Sublingual Dexmedetomidine For Moderate To Severe Agitation In Inpatients With Schizophrenia Or Bipolar Disorder

Study Overview
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Brief Summary
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An open-label, randomized, active control inpatient trial to evaluate the efficacy and tolerability of sublingual dexmedetomidine for the treatment of agitation in inpatients with schizophrenia or bipolar disorder as measured by the Positive and Negative Syndrome Scale - Excited Component (PANSS-EC) and Agitation-Calmness Evaluation Scale (ACES). Lorazepam will serve as the active control.

Detailed Description
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This is an open-label, randomized control trial where patients (N=32) with schizophrenia or bipolar disorder are randomized to receive either sublingual dexmedetomidine or oral lorazepam monotherapy for the treatment of episodic agitation. For moderate agitation (PANSS-EC score ≥14 and <20), patients will receive either sublingual dexmedetomidine 120mcg or oral lorazepam 2mg. For severe agitation (PANSS-EC ≥20), patients will receive either sublingual dexmedetomidine 180mcg or oral lorazepam 2mg. The PANSS-EC and ACES will be evaluated at baseline and after 15, 30, 60, and 120 minutes.

Official Title
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An Open-Label, Randomized, Active Controlled Inpatient Trial Evaluating Sublingual Dexmedetomidine For Moderate To Severe Agitation In Inpatients With Schizophrenia Or Bipolar Disorder

Conditions
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Schizophrenia Agitation, Schizo Affective Disorder, Bipolar Disorder, Dexmedetomidine

Intervention / Treatment
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* Drug: Dexmedetomidine
* Drug: Lorazepam 2 MG/ML


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant is an adult between the ages of 18-55 at the time of study participation Hospitalized on an inpatient unit at Episcopal Hospital Meet the DSM-5 criteria for schizophrenia, schizoaffective disorder, or bipolar disorder, as determined by routine clinical assessment conducted upon admission. Are able to understand and read English Are able to provide informed consent Experiencing a moderate (PANSS-EC score ≥14 and <20) or severe (PANSS-EC score ≥20) episode of agitation Exclusion Criteria: Women who are pregnant or breastfeeding Prisoners Participant has an allergy to dexmedetomidine or lorazepam Participant has mild, moderate or severe hepatic impairment Participant has active pulmonary disease and is receiving treatment (oxygen, inhalers) Individual is currently prescribed scheduled benzodiazepines or methadone Participant history of QTc ≥ 500 msec or a history of arrythmia Participant recent (within the last 2 days) fall, syncope (passing out), feeling lightheaded, or pulse <50. Individual has a history of hypokalemia or hypomagnesemia within the past 2 years? Participant is receiving high-risk medications, including: Methadone Midazolam Opioids High risk medications associated with the QT interval prolongation (sertindole, chlorpromazine, ziprasidone), (amiodarone, iboga, quinine, arsenic, ibutilide, selpercatinib, ivosidenib, bedaquiline, lenvatinib, sotalol, levoketoconazole, cisapride, vendetanib, mobocertinib, disopyramide, papaverine)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexmedetomidine<br>Participants with moderate agitation will receive sublingual dexmedetomidine 120 mcg as needed. Participants with severe agitation will receive dexmedetomidine 180 mcg as needed. | Drug: Dexmedetomidine<br>* Moderate agitation: 120 mcg Severe agitation: 180 mcg<br>* Other names: Igalmi;|
| Active Comparator: Lorazapem<br>Participants with moderate agitation will receive oral lorazapam 2 mgas needed. Participants with severe agitation will receive oral lorazapam 2 mg as needed. | Drug: Lorazepam 2 MG/ML<br>* 2 mg<br>* Other names: Ativan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PANSS-EC score at 120 minutes after medication administration | Severity of agitation will be determined by administering the Positive and Negative Syndrome Scale - Excited Component (PANSS-EC). Moderate to severe agitation will be defined as a PANSS-EC score >=14 and <20; and >= 20 is severe agitation. | Baseline and at 120 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in ACES score at 15, 30, 60, 90, and 120 minutes, or prior to receipt of any rescue medication for agitation. | Severity of agitation will be measured using the standardized Agitation-Calmness Evaluation Scale. The 9-point scale indicated the degree of agitation as follows: 1=marked agitation, 4=normal behavior, 7 = marked calmness, 9=unarousable. | Baseline and 15, 30, 60, 90, and 120 minutes | 
| Change in PANSS-EC score at 15, 30, 60, and 90 minutes, or prior to receipt of any rescue medication for agitation. | Severity of agitation will be determined by administering the Positive and Negative Syndrome Scale - Excited Component (PANSS-EC). Moderate to severe agitation will be defined as a PANSS-EC score >=14 and <20; and >= 20 is severe agitation. | Baseline and 15, 30, 60, and 90 minutes | 
| Patient tolerability assessed by adverse events of dexmedetomidine | Tolerability and safety of sublingual dexmedetomidine was assessed by evaluating spontaneously-reported adverse events. Treatment tolerability as assessed by adverse events will be tabulated by toxicity grade and organ systems as well as overall. | Baseline through 120 minutes after medication administration | 
| Patient satisfaction based on Medication Satisfaction Questionnaire (MSQ) | Medication Satisfaction Questionnaire (MSQ) will be given to the subject to assess their satisfaction of their agitation medication two hours after initial medication administration. The Medication Satisfaction Questionnaire is a 7-point scale, with 1 being Extremely Dissatisfied, 4 being Neither Satisfied or Dissatisfied, and 7 being Extremely Satisfied | Administered 120 minutes after medication administration | 
| Assess the need for rescue medication for agitation within two hours of medication administration | Need for rescue medication of sublingual dexmedetomidine will be assessed by reviewing the Medication Administration Reconciliation (MAR) available on the electronic medical record system for the two hour period of time following medication administration. | Baseline and 2 hours after medication administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Agitation, Schizophrenia, Schizoaffective Disorder, Bipolar Disorder