Dexmedetomidine (Precedex®) for Severe Alcohol Withdrawal Syndrome (AWS) and Alcohol Withdrawal Delirium (AWD)

• Sponsor: Denver Health and Hospital Authority (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01362205
• Collaborator: (none)
• Enrollment: 49
• Locations: 7
• Arms: 2
• Duration (Months): 54
• Patients Per Site: 7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a prospective, randomized, double-blind, placebo-controlled, parallel-group study of dexmedetomidine versus placebo, with lorazepam rescue, for the management of severe alcohol withdrawal syndrome (AWS) and alcohol withdrawal delirium (AWD) in critically ill adults.

The investigators hypothesize that the integration of dexmedetomidine (Precedex®) with usual therapy for the management of severe alcohol withdrawal syndrome (AWS) and alcohol withdrawal delirium/delirium tremens (AWD) in critically ill adult patients will reduce the time to resolution of AWS/AWD, increase the number of delirium-free and ventilator-free days in the first 28 days of hospitalization, reduce the length of ICU and hospital stays, and improve neurocognitive and quality of life scores on hospital discharge.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Withdrawal Delirium; Alcohol Withdrawal Associated Autonomic Hyperactivity; Alcohol Withdrawal Hallucinosis; Alcohol Withdrawal-Induced Delirium Tremens	Drug: Dexmedetomidine; Drug: Placebos	Phase 4

Detailed Description

Severe alcohol withdrawal syndrome (AWS) and alcohol withdrawal delirium (AWD) are frequent principal indication/s for admission to intensive care units. Additionally, unanticipated alcohol withdrawal complicates other critical illnesses and peri-operative states. Alcohol intoxication and withdrawal syndrome are characterized by classic symptoms of adrenergic activation, psychiatric agitation including seizures, as well as metabolic and respiratory dysfunction. The majority of patients with severe AWS are effectively managed with combinations of benzodiazepine (BZD) sedatives (e.g. lorazepam) and butyrophenone antipsychotics (e.g. haloperidol) and require intensive care admission for 2-3 days. However, almost 25% of patients with SAWS have a prolonged critical care course, often complicated by respiratory failure and associated with excessive sedation and risk for complications such as ventilator-associated pneumonia (VAP). AWS is frequently difficult to manage with usual care including benzodiazepines. Additionally, while intermittent bolus dose sedation is recommended for AWS, high dose BZD alone is associated with excessive respiratory suppression and metabolic acidosis. Such therapy increases the likelihood of respiratory failure with its attendant complications of hospital acquired pneumonia and sepsis. Further, patients with underlying chronic liver disease are at greater risk for prolonged sedative effects of BZD and progression of hepatic encephalopathy. The requirement for mechanical ventilation additionally prolongs the course of treatment for AWD because of the need for prolonged sedation. Strategies to control AWS/AWD that control symptoms but avoid adverse effects of excessive respiratory suppression are anticipated to improve the short and medium-term outcomes of AWS.

BZD infusions have also been shown by several investigators to result in excessive and prolonged sedation. However, reasonable alternatives for effective control of psychomotor and adrenergic activation have until recently, been unavailable. The centrally acting alpha-2 receptor agonist, clonidine has been suggested as a useful adjunctive therapy to BZD. However, clonidine is only a mild sedative and can result in significant hemodynamic compromise. By contrast, dexmedetomidine (Precedex), a more potent alpha-2 receptor agonist, is potentially a more effective adjunctive therapy. Precedex is currently marketed in the USA for short-term use as a potent peri-operative sedative and analgesic. This agent has a short circulating half-life and has significantly fewer hemodynamic side effects than clonidine. In addition to its cardiovascular properties, dexmedetomidine possesses anxiolytic, hypnotic/sedative, anesthetic-sparing and analgesic actions and is devoid of significant respiratory depressant effects.

Precedex has been shown to be a safe and effective single agent sedative for critically ill medical and surgical patients in prolonged infusions up to thirty days and is associated with significantly lower incidence of delirium than sedation with the benzodiazepine, midazolam. Preclinical experience and case reports suggest anecdotally Precedex may be of particular benefit in patients with SAWS.

Measures of sedation and delirium will be assessed with the Minnesota Detoxification Scale (MINDS) derived for use in critically ill adults from the validated Clinical Institute Withdrawal Assessment (CIWA-r) scale.

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Dexmedetomidine (Precedex®), With Lorazepam Rescue, for the Management of Severe Alcohol Withdrawal Syndrome (AWS) and Alcohol Withdrawal Delirium (AWD)
• Study Start Date: Mar 1, 2012
• Actual Primary Completion Date: Dec 1, 2015
• Actual Study Completion Date: Sep 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dexmedetomidine Dexmedetomidine titrated to achieve predefined goals on selected components of the MINDS score using the minimum amount of medication possible. Blinded study medication will be started at a rate determined by the MINDS score. The maximum infusion rate is 1.4 μg/kg per hour. Uncontrolled SAWS/D symptoms, will be treated with open label lorazepam according to the MINDS score algorithm. Persistent SAWS/D symptoms despite maximum infusion rate of study medication treatment limiting symptoms while receiving higher infusion rates of study medication, ancillary therapies will be administered according to the MINDS score algorithm, at the discretion of the treating physician.	Drug: Dexmedetomidine; Other Names: Precedex
Placebo Comparator: Placebo Blinded placebo study drug administration in equal volume per hour as active study medication arm.	Drug: Placebos; Inactive placebo (normal saline)

Outcome Measures

Primary Outcome Measures

1. The Length of ICU Stay Defined as the Time Between Randomization and ICU Transfer Orders. [up to 28 days in hours]

Secondary Outcome Measures

1. Average MINDS Score [up to 28 days]

   Minnesota Detoxification Scale (MINDS) min score 0, max score 46. The higher the score, the worse the symptoms of AWS/AWD.

2. The Number of CAM-ICU Negative Days After Randomization. [up to 28 days]

   The Confusion Assessment Method (CAM)-ICU is a validated instrument used to detect the presence or absence of delirium in the ICU. A delirium free day is counted for any day a patient is negative by the CAM-ICU. The higher the number of CAM-ICU negative days indicates the more days a patient was able to think clearly.

3. Number of Ventilator Free Days After Randomization. [up to 28 days]

   A ventilator day is counted for any use of invasive mechanical ventilation during a calendar day

4. The Length in Days of the Hospital Stay [up to 28 days]

   A hospital day is counted for any time on a calendar day the patient is admitted to the hospital. Hospital days are inclusive of ICU days.

5. Scores at Hospital Discharge on the Mini Mental Exam. [up to 28 days]

   The Mini Mental State Examination or Folstein test is a validated 30-point questionnaire used to measure cognitive impairment (min score 0, max score 30). A score of 24 points (out of a max of 30) indicates normal cognition, less than or equal to 9 points indicates severe impairment, 10-18 indicates moderate impairment and 19-23 mild impairment.

6. Scores at Hospital Discharge on the Beck Depression Inventory. [Up to 28 days.]

   The Beck Depression Inventory is a validated questionnaire used to measure severity of depression (min score 0, max score 63). The higher the score the greater the severity of depression. A score of 30-63 indicates severe depression, 19-29 moderate depression, 10-18 mild depression and 0-9 minimal depression.

7. Scores at Hospital Discharge on the Beck Anxiety Inventory [Up to 28 days.]

   The Beck Anxiety Inventory is a validated questionnaire used to measure severity of anxiety (min score 0, max score 63). The higher the score the greater the severity of anxiety. A score of 30-63 indicates severe anxiety, 17-29 moderate anxiety, 10-16 mild anxiety and 0-9 minimal anxiety.

8. Scores at Hospital Discharge on the PTSD Civilian Checklist [Up to 28 days]

   PTSD checklist consists of 17 questions graded on a scale of 1 to 5. The PTSD score is comprised from the sum of the scores 17 questions. The PTSD score has possible values from to 17 to 85 with higher values indicating greater symptom severity.

9. Resource Utilization Costs Associated With This Hospitalization Billed by Physicians. [up to 28 Days]

10. Resource Utilization Costs Associated With This Hospitalization Billed by Facility. [Up to 28 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 89 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female patients, 18 years or older, with severe AWS or AWD per DSM-IV definitions (below) requiring admission to the ICU for medical management

• Ability to provide informed consent (via a proxy decision maker or patient).

• Within 96 hours of ICU admission.

• Meets DSM-IV diagnostic criteria for 291.8 Alcohol Withdrawal Syndrome:

• Cessation of (or reduction in) alcohol use that has been heavy and prolonged.

• Two (or more) of the following, developing within several hours to a few days after Criterion A:

1. autonomic hyperactivity (e.g., sweating or pulse rate greater than 100)

2. increased hand tremor

3. insomnia

4. nausea or vomiting

5. transient visual, tactile, or auditory hallucinations or illusions

6. psychomotor agitation

7. anxiety

8. grand mal seizures

• The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder.

AND Meets DSM-IV diagnostic criteria for 291.0 Alcohol Intoxication or Withdrawal Delirium

• Disturbance of consciousness

• A change in cognition

• The disturbance develops over a short time and can fluctuate

• Onset is temporal associated with Alcohol Withdrawal Syndrome

Exclusion Criteria:

• Age < 18 years

• Physician anticipates ICU transfer orders in less than 12 hours from time of consent.

• Recent traumatic brain injury

• Active status epilepticus

• Pregnancy or lactation

• Known allergy or adverse response to any of the study medications

• Requiring glucocorticoid therapy for treatment of acute hepatitis or Stage III (advanced) decompensated liver failure and encephalopathy

• Trauma or burns as admitting diagnoses

• Neuromuscular blockade other than for intubation

• Epidural or spinal analgesia

• General anesthesia 24 hours prior to, or planned after, the start of study drug infusion

• Serious central nervous system pathology (acute stroke, uncontrolled seizures, severe dementia),

• Unstable angina or acute myocardial infarction

• Left ventricular ejection fraction less than 30%

• Heart rate less than 50/min

• Second- or third degree heart block

• Systolic blood pressure less than 90 mm Hg despite continuous infusions of 2 vasopressors before the start of study drug infusion.

• Previous randomization into this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Hospital Central	Colorado Springs	Colorado	United States	80909
2	Memorial Hospital North	Colorado Springs	Colorado	United States	80920
3	Denver Health Medical Center, Medical ICU	Denver	Colorado	United States	80204
4	Porter Adventist Hospital	Denver	Colorado	United States	80210
5	St. Anthony Hospital	Lakewood	Colorado	United States	80228
6	Louisiana State University	New Orleans	Louisiana	United States	70112
7	Ben Taub Hospital	Houston	Texas	United States	77030

Sponsors and Collaborators

• Denver Health and Hospital Authority

Investigators

• Principal Investigator: Ivor S Douglas, MD, FRCP, Denver Health Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

• Darrouj J, Puri N, Prince E, Lomonaco A, Spevetz A, Gerber DR. Dexmedetomidine infusion as adjunctive therapy to benzodiazepines for acute alcohol withdrawal. Ann Pharmacother. 2008 Nov;42(11):1703-5. doi: 10.1345/aph.1K678. Epub 2008 Sep 9.
• Maccioli GA. Dexmedetomidine to facilitate drug withdrawal. Anesthesiology. 2003 Feb;98(2):575-7.
• Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F, Whitten P, Margolis BD, Byrne DW, Ely EW, Rocha MG; SEDCOM (Safety and Efficacy of Dexmedetomidine Compared With Midazolam) Study Group. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009 Feb 4;301(5):489-99. doi: 10.1001/jama.2009.56. Epub 2009 Feb 2.
• Rovasalo A, Tohmo H, Aantaa R, Kettunen E, Palojoki R. Dexmedetomidine as an adjuvant in the treatment of alcohol withdrawal delirium: a case report. Gen Hosp Psychiatry. 2006 Jul-Aug;28(4):362-3.

• Responsible Party: Ivor Douglas, Professor of Medicine, Denver Health and Hospital Authority
• ClinicalTrials.gov Identifier: NCT01362205
• Other Study ID Numbers: COMIRB 09-0822
• First Posted: May 30, 2011
• Last Update Posted: Nov 6, 2017
• Last Verified: Oct 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Ivor Douglas, Professor of Medicine, Denver Health and Hospital Authority: Severe Alcohol Withdrawal Delirium Tremens
• Additional relevant MeSH terms: Delirium; Alcohol Withdrawal Delirium; Substance Withdrawal Syndrome; Dexmedetomidine

Study Results

Participant Flow

Arm/Group Title	Dexmedetomidine	Placebo
Arm/Group Description	Dexmedetomidine titrated to achieve predefined goals on selected components of the MINDS score using the minimum amount of medication possible. Blinded study medication will be started at a rate determined by the MINDS score. The maximum infusion rate is 1.4 μg/kg per hour. Uncontrolled SAWS/D symptoms, will be treated with open label lorazepam according to the MINDS score algorithm. Persistent SAWS/D symptoms despite maximum infusion rate of study medication treatment limiting symptoms while receiving higher infusion rates of study medication, ancillary therapies will be administered according to the MINDS score algorithm, at the discretion of the treating physician. Dexmedetomidine: See arm details	Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
Period Title: Overall Study
STARTED	22	27
COMPLETED	22	27
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Dexmedetomidine	Placebo	Total
Arm/Group Description	Dexmedetomidine titrated to achieve predefined goals on selected components of the MINDS score using the minimum amount of medication possible. Blinded study medication will be started at a rate determined by the MINDS score. The maximum infusion rate is 1.4 μg/kg per hour. Uncontrolled SAWS/D symptoms, will be treated with open label lorazepam according to the MINDS score algorithm. Persistent SAWS/D symptoms despite maximum infusion rate of study medication treatment limiting symptoms while receiving higher infusion rates of study medication, ancillary therapies will be administered according to the MINDS score algorithm, at the discretion of the treating physician. Dexmedetomidine: See arm details	Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%	Total of all reporting groups
Overall Participants	22	27	49
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.5 (11.54)	48.2 (11.82)	47.4 (11.61)
Sex: Female, Male (Count of Participants)
Female	6 27.3%	3 11.1%	9 18.4%
Male	16 72.7%	24 88.9%	40 81.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 9.1%	8 29.6%	10 20.4%
Not Hispanic or Latino	20 90.9%	19 70.4%	39 79.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 3.7%	1 2%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 13.6%	2 7.4%	5 10.2%
White	19 86.4%	24 88.9%	43 87.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	22 100%	27 100%	49 100%

Outcome Measures

1. Primary Outcome

Title	The Length of ICU Stay Defined as the Time Between Randomization and ICU Transfer Orders.
Time Frame	up to 28 days in hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dexmedetomidine	Placebo
Arm/Group Description	Dexmedetomidine titrated to achieve predefined goals on selected components of the MINDS score using the minimum amount of medication possible. Blinded study medication will be started at a rate determined by the MINDS score. The maximum infusion rate is 1.4 μg/kg per hour. Uncontrolled SAWS/D symptoms, will be treated with open label lorazepam according to the MINDS score algorithm. Persistent SAWS/D symptoms despite maximum infusion rate of study medication treatment limiting symptoms while receiving higher infusion rates of study medication, ancillary therapies will be administered according to the MINDS score algorithm, at the discretion of the treating physician. Dexmedetomidine: See arm details	Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
Measure Participants	22	27
Median (Inter-Quartile Range) [hours]	79.2	104.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dexmedetomidine, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2454
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Average MINDS Score
Description	Minnesota Detoxification Scale (MINDS) min score 0, max score 46. The higher the score, the worse the symptoms of AWS/AWD.
Time Frame	up to 28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dexmedetomidine	Placebo
Arm/Group Description	Dexmedetomidine titrated to achieve predefined goals on selected components of the MINDS score using the minimum amount of medication possible. Blinded study medication will be started at a rate determined by the MINDS score. The maximum infusion rate is 1.4 μg/kg per hour. Uncontrolled SAWS/D symptoms, will be treated with open label lorazepam according to the MINDS score algorithm. Persistent SAWS/D symptoms despite maximum infusion rate of study medication treatment limiting symptoms while receiving higher infusion rates of study medication, ancillary therapies will be administered according to the MINDS score algorithm, at the discretion of the treating physician. Dexmedetomidine: See arm details	Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
Measure Participants	22	27
Median (Inter-Quartile Range) [units on a scale]	8.2	9.4

3. Secondary Outcome

Title	The Number of CAM-ICU Negative Days After Randomization.
Description	The Confusion Assessment Method (CAM)-ICU is a validated instrument used to detect the presence or absence of delirium in the ICU. A delirium free day is counted for any day a patient is negative by the CAM-ICU. The higher the number of CAM-ICU negative days indicates the more days a patient was able to think clearly.
Time Frame	up to 28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dexmedetomidine	Placebo
Arm/Group Description	Dexmedetomidine titrated to achieve predefined goals on selected components of the MINDS score using the minimum amount of medication possible. Blinded study medication will be started at a rate determined by the MINDS score. The maximum infusion rate is 1.4 μg/kg per hour. Uncontrolled SAWS/D symptoms, will be treated with open label lorazepam according to the MINDS score algorithm. Persistent SAWS/D symptoms despite maximum infusion rate of study medication treatment limiting symptoms while receiving higher infusion rates of study medication, ancillary therapies will be administered according to the MINDS score algorithm, at the discretion of the treating physician. Dexmedetomidine: See arm details	Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
Measure Participants	22	27
Median (Inter-Quartile Range) [days]	0.3	0.3

4. Secondary Outcome

Title	Number of Ventilator Free Days After Randomization.
Description	A ventilator day is counted for any use of invasive mechanical ventilation during a calendar day
Time Frame	up to 28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dexmedetomidine	Placebo
Arm/Group Description	Dexmedetomidine titrated to achieve predefined goals on selected components of the MINDS score using the minimum amount of medication possible. Blinded study medication will be started at a rate determined by the MINDS score. The maximum infusion rate is 1.4 μg/kg per hour. Uncontrolled SAWS/D symptoms, will be treated with open label lorazepam according to the MINDS score algorithm. Persistent SAWS/D symptoms despite maximum infusion rate of study medication treatment limiting symptoms while receiving higher infusion rates of study medication, ancillary therapies will be administered according to the MINDS score algorithm, at the discretion of the treating physician. Dexmedetomidine: See arm details	Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
Measure Participants	22	27
Median (Inter-Quartile Range) [days]	27.5	28.0

5. Secondary Outcome

Title	The Length in Days of the Hospital Stay
Description	A hospital day is counted for any time on a calendar day the patient is admitted to the hospital. Hospital days are inclusive of ICU days.
Time Frame	up to 28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dexmedetomidine	Placebo
Arm/Group Description	Dexmedetomidine titrated to achieve predefined goals on selected components of the MINDS score using the minimum amount of medication possible. Blinded study medication will be started at a rate determined by the MINDS score. The maximum infusion rate is 1.4 μg/kg per hour. Uncontrolled SAWS/D symptoms, will be treated with open label lorazepam according to the MINDS score algorithm. Persistent SAWS/D symptoms despite maximum infusion rate of study medication treatment limiting symptoms while receiving higher infusion rates of study medication, ancillary therapies will be administered according to the MINDS score algorithm, at the discretion of the treating physician. Dexmedetomidine: See arm details	Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
Measure Participants	22	27
Median (Inter-Quartile Range) [days]	8.0	12.0

6. Secondary Outcome

Title	Scores at Hospital Discharge on the Mini Mental Exam.
Description	The Mini Mental State Examination or Folstein test is a validated 30-point questionnaire used to measure cognitive impairment (min score 0, max score 30). A score of 24 points (out of a max of 30) indicates normal cognition, less than or equal to 9 points indicates severe impairment, 10-18 indicates moderate impairment and 19-23 mild impairment.
Time Frame	up to 28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dexmedetomidine	Placebo
Arm/Group Description	Dexmedetomidine titrated to achieve predefined goals on selected components of the MINDS score using the minimum amount of medication possible. Blinded study medication will be started at a rate determined by the MINDS score. The maximum infusion rate is 1.4 μg/kg per hour. Uncontrolled SAWS/D symptoms, will be treated with open label lorazepam according to the MINDS score algorithm. Persistent SAWS/D symptoms despite maximum infusion rate of study medication treatment limiting symptoms while receiving higher infusion rates of study medication, ancillary therapies will be administered according to the MINDS score algorithm, at the discretion of the treating physician. Dexmedetomidine: See arm details	Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
Measure Participants	22	27
Mean (Standard Deviation) [units on a scale]	25.8 (2.53)	23.1 (6.09)

7. Secondary Outcome

Title	Scores at Hospital Discharge on the Beck Depression Inventory.
Description	The Beck Depression Inventory is a validated questionnaire used to measure severity of depression (min score 0, max score 63). The higher the score the greater the severity of depression. A score of 30-63 indicates severe depression, 19-29 moderate depression, 10-18 mild depression and 0-9 minimal depression.
Time Frame	Up to 28 days.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dexmedetomidine	Placebo
Arm/Group Description	Dexmedetomidine titrated to achieve predefined goals on selected components of the MINDS score using the minimum amount of medication possible. Blinded study medication will be started at a rate determined by the MINDS score. The maximum infusion rate is 1.4 μg/kg per hour. Uncontrolled SAWS/D symptoms, will be treated with open label lorazepam according to the MINDS score algorithm. Persistent SAWS/D symptoms despite maximum infusion rate of study medication treatment limiting symptoms while receiving higher infusion rates of study medication, ancillary therapies will be administered according to the MINDS score algorithm, at the discretion of the treating physician. Dexmedetomidine: See arm details	Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
Measure Participants	22	27
Mean (Standard Deviation) [units on a scale]	26.5 (9.14)	21.4 (10.95)

8. Secondary Outcome

Title	Scores at Hospital Discharge on the Beck Anxiety Inventory
Description	The Beck Anxiety Inventory is a validated questionnaire used to measure severity of anxiety (min score 0, max score 63). The higher the score the greater the severity of anxiety. A score of 30-63 indicates severe anxiety, 17-29 moderate anxiety, 10-16 mild anxiety and 0-9 minimal anxiety.
Time Frame	Up to 28 days.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dexmedetomidine	Placebo
Arm/Group Description	Dexmedetomidine titrated to achieve predefined goals on selected components of the MINDS score using the minimum amount of medication possible. Blinded study medication will be started at a rate determined by the MINDS score. The maximum infusion rate is 1.4 μg/kg per hour. Uncontrolled SAWS/D symptoms, will be treated with open label lorazepam according to the MINDS score algorithm. Persistent SAWS/D symptoms despite maximum infusion rate of study medication treatment limiting symptoms while receiving higher infusion rates of study medication, ancillary therapies will be administered according to the MINDS score algorithm, at the discretion of the treating physician. Dexmedetomidine: See arm details	Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
Measure Participants	22	27
Mean (Standard Deviation) [units on a scale]	30.3 (10.83)	21.6 (11.55)

9. Secondary Outcome

Title	Scores at Hospital Discharge on the PTSD Civilian Checklist
Description	PTSD checklist consists of 17 questions graded on a scale of 1 to 5. The PTSD score is comprised from the sum of the scores 17 questions. The PTSD score has possible values from to 17 to 85 with higher values indicating greater symptom severity.
Time Frame	Up to 28 days

Outcome Measure Data

Analysis Population Description

The number of participants analyzed was lower than the total included as many patients were discharged quickly upon resolution of altered mental status when a research team member was unavailable to administer the questionnaires.

Arm/Group Title	Dexmedetomidine	Placebo
Arm/Group Description	Dexmedetomidine titrated to achieve predefined goals on selected components of the MINDS score using the minimum amount of medication possible. Blinded study medication will be started at a rate determined by the MINDS score. The maximum infusion rate is 1.4 μg/kg per hour. Uncontrolled SAWS/D symptoms, will be treated with open label lorazepam according to the MINDS score algorithm. Persistent SAWS/D symptoms despite maximum infusion rate of study medication treatment limiting symptoms while receiving higher infusion rates of study medication, ancillary therapies will be administered according to the MINDS score algorithm, at the discretion of the treating physician. Dexmedetomidine: See arm details	Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
Measure Participants	8	12
Median (Inter-Quartile Range) [units on a scale]	45.5	32.5

10. Secondary Outcome

Title	Resource Utilization Costs Associated With This Hospitalization Billed by Physicians.
Time Frame	up to 28 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dexmedetomidine	Placebo
Arm/Group Description	Dexmedetomidine titrated to achieve predefined goals on selected components of the MINDS score using the minimum amount of medication possible. Blinded study medication will be started at a rate determined by the MINDS score. The maximum infusion rate is 1.4 μg/kg per hour. Uncontrolled SAWS/D symptoms, will be treated with open label lorazepam according to the MINDS score algorithm. Persistent SAWS/D symptoms despite maximum infusion rate of study medication treatment limiting symptoms while receiving higher infusion rates of study medication, ancillary therapies will be administered according to the MINDS score algorithm, at the discretion of the treating physician. Dexmedetomidine: See arm details	Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
Measure Participants	22	27
Median (Inter-Quartile Range) [Dollar (United States)]	3482	4461

11. Secondary Outcome

Title	Resource Utilization Costs Associated With This Hospitalization Billed by Facility.
Time Frame	Up to 28 days

Outcome Measure Data

Analysis Population Description

The overall number of participants analyzed is less than the number randomized as data was not available for research use at many of the participating institutions.

Arm/Group Title	Dexmedetomidine	Placebo
Arm/Group Description	Dexmedetomidine titrated to achieve predefined goals on selected components of the MINDS score using the minimum amount of medication possible. Blinded study medication will be started at a rate determined by the MINDS score. The maximum infusion rate is 1.4 μg/kg per hour. Uncontrolled SAWS/D symptoms, will be treated with open label lorazepam according to the MINDS score algorithm. Persistent SAWS/D symptoms despite maximum infusion rate of study medication treatment limiting symptoms while receiving higher infusion rates of study medication, ancillary therapies will be administered according to the MINDS score algorithm, at the discretion of the treating physician. Dexmedetomidine: See arm details	Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
Measure Participants	17	23
Median (Inter-Quartile Range) [USD]	81234	91651

Adverse Events

Time Frame	The first 28 days of hospitalization after randomization.
Adverse Event Reporting Description	One subject randomized to the dexmedetomidine group did not receive study drug and so was excluded from the adverse event analysis. The total number of subjects included in the adverse event analysis in the dexmedetomidine decreased from 22 to 21.
Arm/Group Title	Dexmedetomidine		Placebo
Arm/Group Description	Dexmedetomidine titrated to achieve predefined goals on selected components of the MINDS score using the minimum amount of medication possible. Blinded study medication will be started at a rate determined by the MINDS score. The maximum infusion rate is 1.4 μg/kg per hour. Uncontrolled SAWS/D symptoms, will be treated with open label lorazepam according to the MINDS score algorithm. Persistent SAWS/D symptoms despite maximum infusion rate of study medication treatment limiting symptoms while receiving higher infusion rates of study medication, ancillary therapies will be administered according to the MINDS score algorithm, at the discretion of the treating physician. Dexmedetomidine: See arm details		Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
All Cause Mortality
	Dexmedetomidine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/27 (0%)
Serious Adverse Events
	Dexmedetomidine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/21 (23.8%)		3/27 (11.1%)
Cardiac disorders
Atrial fibrillation	1/21 (4.8%)		0/27 (0%)
Cardiac arrest	1/21 (4.8%)		0/27 (0%)
Hepatobiliary disorders
Hepatitis alcoholic	1/21 (4.8%)		0/27 (0%)
Infections and infestations
Bacteraemia	0/21 (0%)		1/27 (3.7%)
Enterococcal infection	1/21 (4.8%)		0/27 (0%)
Pneumonia	0/21 (0%)		1/27 (3.7%)
Septic shock	1/21 (4.8%)		1/27 (3.7%)
Nervous system disorders
Haemorrhage intracranial	1/21 (4.8%)		0/27 (0%)
Osmotic demyelination syndrome	1/21 (4.8%)		0/27 (0%)
Renal and urinary disorders
Acute kidney injury	1/21 (4.8%)		0/27 (0%)
Respiratory, thoracic and mediastinal disorders
Aspiration	0/21 (0%)		1/27 (3.7%)
Respiratory failure	2/21 (9.5%)		1/27 (3.7%)
Other (Not Including Serious) Adverse Events
	Dexmedetomidine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/21 (57.1%)		17/27 (63%)
Blood and lymphatic system disorders
Leukocytosis	3/21 (14.3%)		1/27 (3.7%)
Thrombocytosis	1/21 (4.8%)		4/27 (14.8%)
Cardiac disorders
Bradycardia	2/21 (9.5%)		1/27 (3.7%)
Gastrointestinal disorders
Diarrhoea	3/21 (14.3%)		4/27 (14.8%)
General disorders
Oedema peripheral	6/21 (28.6%)		11/27 (40.7%)
Pyrexia	4/21 (19%)		3/27 (11.1%)
Infections and infestations
Urinary tract infection	0/21 (0%)		2/27 (7.4%)
Injury, poisoning and procedural complications
Laceration	0/21 (0%)		2/27 (7.4%)
Skin abrasion	1/21 (4.8%)		2/27 (7.4%)
Investigations
Alanine aminotransferase increased	1/21 (4.8%)		3/27 (11.1%)
Haemoglobin decreased	0/21 (0%)		3/27 (11.1%)
Platelet count decreased	1/21 (4.8%)		3/27 (11.1%)
Protein total decreased	0/21 (0%)		3/27 (11.1%)
Metabolism and nutrition disorders
Hyperkalaemia	0/21 (0%)		2/27 (7.4%)
Hypermagnesaemia	2/21 (9.5%)		1/27 (3.7%)
Hypernatraemia	1/21 (4.8%)		4/27 (14.8%)
Hyperphosphataemia	1/21 (4.8%)		3/27 (11.1%)
Hypoalbuminaemia	1/21 (4.8%)		4/27 (14.8%)
Hypocalcaemia	1/21 (4.8%)		2/27 (7.4%)
Hypokalaemia	10/21 (47.6%)		16/27 (59.3%)
Hypomagnesaemia	1/21 (4.8%)		4/27 (14.8%)
Hyponatraemia	2/21 (9.5%)		1/27 (3.7%)
Hypophosphataemia	3/21 (14.3%)		5/27 (18.5%)
Respiratory, thoracic and mediastinal disorders
Cough	2/21 (9.5%)		0/27 (0%)
Skin and subcutaneous tissue disorders
Ecchymosis	1/21 (4.8%)		3/27 (11.1%)
Vascular disorders
Deep vein thrombosis	0/21 (0%)		2/27 (7.4%)
Hypertension	5/21 (23.8%)		13/27 (48.1%)
Hypotension	6/21 (28.6%)		4/27 (14.8%)

Limitations/Caveats

Early termination due to slow enrollment leading to small numbers of subjects analyzed

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.