Trial Outcomes & Findings for Dexmedetomidine (Precedex®) for Severe Alcohol Withdrawal Syndrome (AWS) and Alcohol Withdrawal Delirium (AWD) (NCT NCT01362205)

NCT ID: NCT01362205

Last Updated: 2017-11-06

Results Overview

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

49 participants

Primary outcome timeframe

up to 28 days in hours

Results posted on

2017-11-06

Participant Flow

Participant milestones

Participant milestones
Measure	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. Dexmedetomidine: See arm details	Placebo Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
Overall Study STARTED	22	27
Overall Study COMPLETED	22	27
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dexmedetomidine n=22 Participants 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	Placebo n=27 Participants Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%	Total n=49 Participants Total of all reporting groups
Age, Continuous	46.5 years STANDARD_DEVIATION 11.54 • n=5 Participants	48.2 years STANDARD_DEVIATION 11.82 • n=7 Participants	47.4 years STANDARD_DEVIATION 11.61 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	24 Participants n=7 Participants	40 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	8 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=5 Participants	19 Participants n=7 Participants	39 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	19 Participants n=5 Participants	24 Participants n=7 Participants	43 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	22 participants n=5 Participants	27 participants n=7 Participants	49 participants n=5 Participants

PRIMARY outcome

Timeframe: up to 28 days in hours

Outcome measures

Outcome measures
Measure	Dexmedetomidine n=22 Participants 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	Placebo n=27 Participants Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
The Length of ICU Stay Defined as the Time Between Randomization and ICU Transfer Orders.	79.2 hours Interval 43.9 to 134.6	104.9 hours Interval 63.7 to 183.1

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Dexmedetomidine n=22 Participants 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	Placebo n=27 Participants Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
Average MINDS Score	8.2 units on a scale Interval 4.6 to 11.0	9.4 units on a scale Interval 7.8 to 11.6

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Dexmedetomidine n=22 Participants 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	Placebo n=27 Participants Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
The Number of CAM-ICU Negative Days After Randomization.	0.3 days Interval 0.0 to 0.5	0.3 days Interval 0.1 to 0.7

SECONDARY outcome

Timeframe: up to 28 days

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

Outcome measures

Outcome measures
Measure	Dexmedetomidine n=22 Participants 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	Placebo n=27 Participants Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
Number of Ventilator Free Days After Randomization.	27.5 days Interval 25.0 to 28.0	28.0 days Interval 26.0 to 28.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Dexmedetomidine n=22 Participants 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	Placebo n=27 Participants Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
The Length in Days of the Hospital Stay	8.0 days Interval 5.0 to 13.0	12.0 days Interval 6.0 to 16.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Dexmedetomidine n=22 Participants 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	Placebo n=27 Participants Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
Scores at Hospital Discharge on the Mini Mental Exam.	25.8 units on a scale Standard Deviation 2.53	23.1 units on a scale Standard Deviation 6.09

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Dexmedetomidine n=22 Participants 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	Placebo n=27 Participants Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
Scores at Hospital Discharge on the Beck Depression Inventory.	26.5 units on a scale Standard Deviation 9.14	21.4 units on a scale Standard Deviation 10.95

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Dexmedetomidine n=22 Participants 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	Placebo n=27 Participants Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
Scores at Hospital Discharge on the Beck Anxiety Inventory	30.3 units on a scale Standard Deviation 10.83	21.6 units on a scale Standard Deviation 11.55

SECONDARY outcome

Timeframe: Up to 28 days

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Dexmedetomidine n=8 Participants 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	Placebo n=12 Participants Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
Scores at Hospital Discharge on the PTSD Civilian Checklist	45.5 units on a scale Interval 39.0 to 59.5	32.5 units on a scale Interval 27.5 to 37.0

SECONDARY outcome

Timeframe: up to 28 Days

Outcome measures

Outcome measures
Measure	Dexmedetomidine n=22 Participants 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	Placebo n=27 Participants Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
Resource Utilization Costs Associated With This Hospitalization Billed by Physicians.	3482 Dollar (United States) Interval 2068.0 to 9326.0	4461 Dollar (United States) Interval 2926.0 to 8001.0

SECONDARY outcome

Timeframe: Up to 28 days

Population: 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.

Outcome measures

Outcome measures
Measure	Dexmedetomidine n=17 Participants 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	Placebo n=23 Participants Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
Resource Utilization Costs Associated With This Hospitalization Billed by Facility.	81234 USD Interval 51437.0 to 137272.0	91651 USD Interval 67341.0 to 132458.0

Adverse Events

Dexmedetomidine

Serious events: 5 serious events

Other events: 12 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dexmedetomidine n=21 participants at risk 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	Placebo n=27 participants at risk Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
Cardiac disorders Atrial fibrillation	4.8% 1/21 • The first 28 days of hospitalization after randomization. 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.	0.00% 0/27 • The first 28 days of hospitalization after randomization. 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.
Cardiac disorders Cardiac arrest	4.8% 1/21 • The first 28 days of hospitalization after randomization. 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.	0.00% 0/27 • The first 28 days of hospitalization after randomization. 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.
Hepatobiliary disorders Hepatitis alcoholic	4.8% 1/21 • The first 28 days of hospitalization after randomization. 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.	0.00% 0/27 • The first 28 days of hospitalization after randomization. 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.
Infections and infestations Bacteraemia	0.00% 0/21 • The first 28 days of hospitalization after randomization. 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.	3.7% 1/27 • The first 28 days of hospitalization after randomization. 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.
Infections and infestations Enterococcal infection	4.8% 1/21 • The first 28 days of hospitalization after randomization. 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.	0.00% 0/27 • The first 28 days of hospitalization after randomization. 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.
Infections and infestations Pneumonia	0.00% 0/21 • The first 28 days of hospitalization after randomization. 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.	3.7% 1/27 • The first 28 days of hospitalization after randomization. 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.
Infections and infestations Septic shock	4.8% 1/21 • The first 28 days of hospitalization after randomization. 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.	3.7% 1/27 • The first 28 days of hospitalization after randomization. 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.
Nervous system disorders Haemorrhage intracranial	4.8% 1/21 • The first 28 days of hospitalization after randomization. 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.	0.00% 0/27 • The first 28 days of hospitalization after randomization. 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.
Nervous system disorders Osmotic demyelination syndrome	4.8% 1/21 • The first 28 days of hospitalization after randomization. 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.	0.00% 0/27 • The first 28 days of hospitalization after randomization. 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.
Renal and urinary disorders Acute kidney injury	4.8% 1/21 • The first 28 days of hospitalization after randomization. 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.	0.00% 0/27 • The first 28 days of hospitalization after randomization. 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.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/21 • The first 28 days of hospitalization after randomization. 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.	3.7% 1/27 • The first 28 days of hospitalization after randomization. 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.
Respiratory, thoracic and mediastinal disorders Respiratory failure	9.5% 2/21 • The first 28 days of hospitalization after randomization. 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.	3.7% 1/27 • The first 28 days of hospitalization after randomization. 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.

Other adverse events

Additional Information

Katie Overdier RN

Denver Health Medical Center

Phone: 303 602 1479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Dexmedetomidine n=21 participants at risk 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	Placebo n=27 participants at risk Blinded placebo study drug administration in equal volume per hour as active study medication arm. Placebo: Sterile, clear saline 0.9%
Blood and lymphatic system disorders Leukocytosis	14.3% 3/21 • The first 28 days of hospitalization after randomization. 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.	3.7% 1/27 • The first 28 days of hospitalization after randomization. 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.
Blood and lymphatic system disorders Thrombocytosis	4.8% 1/21 • The first 28 days of hospitalization after randomization. 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.	14.8% 4/27 • The first 28 days of hospitalization after randomization. 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.
Cardiac disorders Bradycardia	9.5% 2/21 • The first 28 days of hospitalization after randomization. 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.	3.7% 1/27 • The first 28 days of hospitalization after randomization. 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.
Gastrointestinal disorders Diarrhoea	14.3% 3/21 • The first 28 days of hospitalization after randomization. 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.	14.8% 4/27 • The first 28 days of hospitalization after randomization. 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.
General disorders Oedema peripheral	28.6% 6/21 • The first 28 days of hospitalization after randomization. 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.	40.7% 11/27 • The first 28 days of hospitalization after randomization. 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.
General disorders Pyrexia	19.0% 4/21 • The first 28 days of hospitalization after randomization. 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.	11.1% 3/27 • The first 28 days of hospitalization after randomization. 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.
Infections and infestations Urinary tract infection	0.00% 0/21 • The first 28 days of hospitalization after randomization. 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.	7.4% 2/27 • The first 28 days of hospitalization after randomization. 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.
Injury, poisoning and procedural complications Laceration	0.00% 0/21 • The first 28 days of hospitalization after randomization. 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.	7.4% 2/27 • The first 28 days of hospitalization after randomization. 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.
Injury, poisoning and procedural complications Skin abrasion	4.8% 1/21 • The first 28 days of hospitalization after randomization. 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.	7.4% 2/27 • The first 28 days of hospitalization after randomization. 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.
Investigations Alanine aminotransferase increased	4.8% 1/21 • The first 28 days of hospitalization after randomization. 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.	11.1% 3/27 • The first 28 days of hospitalization after randomization. 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.
Investigations Haemoglobin decreased	0.00% 0/21 • The first 28 days of hospitalization after randomization. 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.	11.1% 3/27 • The first 28 days of hospitalization after randomization. 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.
Investigations Platelet count decreased	4.8% 1/21 • The first 28 days of hospitalization after randomization. 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.	11.1% 3/27 • The first 28 days of hospitalization after randomization. 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.
Investigations Protein total decreased	0.00% 0/21 • The first 28 days of hospitalization after randomization. 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.	11.1% 3/27 • The first 28 days of hospitalization after randomization. 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.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/21 • The first 28 days of hospitalization after randomization. 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.	7.4% 2/27 • The first 28 days of hospitalization after randomization. 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.
Metabolism and nutrition disorders Hypermagnesaemia	9.5% 2/21 • The first 28 days of hospitalization after randomization. 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.	3.7% 1/27 • The first 28 days of hospitalization after randomization. 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.
Metabolism and nutrition disorders Hypernatraemia	4.8% 1/21 • The first 28 days of hospitalization after randomization. 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.	14.8% 4/27 • The first 28 days of hospitalization after randomization. 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.
Metabolism and nutrition disorders Hyperphosphataemia	4.8% 1/21 • The first 28 days of hospitalization after randomization. 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.	11.1% 3/27 • The first 28 days of hospitalization after randomization. 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.
Metabolism and nutrition disorders Hypoalbuminaemia	4.8% 1/21 • The first 28 days of hospitalization after randomization. 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.	14.8% 4/27 • The first 28 days of hospitalization after randomization. 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.
Metabolism and nutrition disorders Hypocalcaemia	4.8% 1/21 • The first 28 days of hospitalization after randomization. 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.	7.4% 2/27 • The first 28 days of hospitalization after randomization. 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.
Metabolism and nutrition disorders Hypokalaemia	47.6% 10/21 • The first 28 days of hospitalization after randomization. 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.	59.3% 16/27 • The first 28 days of hospitalization after randomization. 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.
Metabolism and nutrition disorders Hypomagnesaemia	4.8% 1/21 • The first 28 days of hospitalization after randomization. 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.	14.8% 4/27 • The first 28 days of hospitalization after randomization. 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.
Metabolism and nutrition disorders Hyponatraemia	9.5% 2/21 • The first 28 days of hospitalization after randomization. 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.	3.7% 1/27 • The first 28 days of hospitalization after randomization. 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.
Metabolism and nutrition disorders Hypophosphataemia	14.3% 3/21 • The first 28 days of hospitalization after randomization. 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.	18.5% 5/27 • The first 28 days of hospitalization after randomization. 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.
Respiratory, thoracic and mediastinal disorders Cough	9.5% 2/21 • The first 28 days of hospitalization after randomization. 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.	0.00% 0/27 • The first 28 days of hospitalization after randomization. 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.
Skin and subcutaneous tissue disorders Ecchymosis	4.8% 1/21 • The first 28 days of hospitalization after randomization. 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.	11.1% 3/27 • The first 28 days of hospitalization after randomization. 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.
Vascular disorders Deep vein thrombosis	0.00% 0/21 • The first 28 days of hospitalization after randomization. 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.	7.4% 2/27 • The first 28 days of hospitalization after randomization. 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.
Vascular disorders Hypertension	23.8% 5/21 • The first 28 days of hospitalization after randomization. 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.	48.1% 13/27 • The first 28 days of hospitalization after randomization. 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.
Vascular disorders Hypotension	28.6% 6/21 • The first 28 days of hospitalization after randomization. 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.	14.8% 4/27 • The first 28 days of hospitalization after randomization. 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.