Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Hospira, now a wholly owned subsidiary of Pfizer | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This study is designed to evaluate dexmedetomidine as adjunctive therapy of severe alcohol withdrawal of medical ICU patients. Specifically, this study will assess whether adjunctive dexmedetomidine reduces the doses of conventional agents used for alcohol withdrawal while maintaining patient comfort and safety and will explore if dexmedetomidine exhibits a dose-dependent profile of action when it is used for this indication. In addition, this study will assess the relationships between alcohol withdrawal, therapy with dexmedetomidine, and potential serum biomarkers of alcohol withdrawal.
The objectives of this randomized, double-blind, placebo controlled, dose escalation study are a) to determine if adding dexmedetomidine to symptom-triggered, standard therapy of severe alcohol withdrawal reduces the dose requirements of conventional sedatives, analgesics, and neuroleptics; maintains patient comfort and safety; and prevents and shortens tracheal intubation; b) to explore whether dexmedetomidine acts in a dose-dependent manner to reduce the dose requirements of conventional sedatives, analgesics, and neuroleptics while maintaining patient comfort; and c) determine the association between alcohol withdrawal and potential serum biomarkers of alcohol withdrawal and assess whether these are expressed differently when dexmedetomidine is used as adjunctive therapy. Dexmedetomidine will be added to existing sedative therapies in an effort to decrease the use of these agents while maintaining patient comfort. The study will randomize twenty-four patients in a double-blind manner to receive placebo or dexmedetomidine at doses of 0.4 or 1.2 µg/kg per hour for a maximum duration of five days. All patients will be managed using an existing institution-specific, symptom-triggered alcohol withdrawal protocol.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dexmedetomidine, low dose | Experimental | Dexmedetomidine 0.4 µg/kg per hour administered for a maximum duration of five days |
|
| Dexmedetomidine, high dose | Experimental | Dexmedetomidine 1.2 µg/kg per hour administered for a maximum duration of five days |
|
| Placebo | Placebo Comparator | Normal saline |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dexmedetomidine | Drug | Dexmedetomidine at 0.4 or 1.2 µg/kg per hour is administered for a maximum duration of five days |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cumulative Lorazepam Dose Over the First Seven Days of Alcohol Withdrawal | Seven days | |
| Change in 12-Hour Lorazepam Requirement Pre- and Post-Treatment | 12 hours before treatment, 12 hours after treatment on first day of starting study drug | |
| Change in 24-Hour Lorazepam Requirement Pre- and Post-Treatment | 24 hours before treatment, 24 hours after treatment on first day of starting study drug |
| Measure | Description | Time Frame |
|---|---|---|
| The Degree of Alcohol Withdrawal Assessed by Clinical Institute Withdrawal Assessment (CIWA) Scores | Proportion of clinical institute withdrawal assessment (CIWA) Scores listed as severe or moderate 24 Hours after Starting Study Drug. All subjects had at least four CIWA assessments.The CIWA is a ten item scale with each item on the scale scored independently on a 0-7 or 0-4 scale, and the summation of the scores yielding an aggregate value that correlates to the severity of alcohol withdrawal. Ranges of scores are from 0 to 67. Mild alcohol withdrawal is defined with a score less than or equal to 15, moderate with scores of 16 to 20, and severe with any score greater than 20. The ten items evaluated include nausea and vomiting, tremor, sweats, anxiety, agitation, tactile disturbances, auditory disturbances, visual disturbances, headache, and orientation. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Robert MacLaren, PharmD | University of Colorado School of Pharmacy | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Colorado Hospital | Aurora | Colorado | 80045 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25638740 | Derived | Reynolds PM, Mueller SW, MacLaren R. A comparison of dexmedetomidine and placebo on the plasma concentrations of NGF, BDNF, GDNF, and epinephrine during severe alcohol withdrawal. Alcohol. 2015 Feb;49(1):15-9. doi: 10.1016/j.alcohol.2014.11.006. Epub 2015 Jan 22. | |
| 24351375 | Derived | Mueller SW, Preslaski CR, Kiser TH, Fish DN, Lavelle JC, Malkoski SP, MacLaren R. A randomized, double-blind, placebo-controlled dose range study of dexmedetomidine as adjunctive therapy for alcohol withdrawal. Crit Care Med. 2014 May;42(5):1131-9. doi: 10.1097/CCM.0000000000000141. |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Dexmedetomidine, Low Dose | Dexmedetomidine 0.4 µg/kg per hour administered for a maximum duration of five days Dexmedetomidine: Dexmedetomidine at 0.4 or 1.2 µg/kg per hour is administered for a maximum duration of five days |
| FG001 | Dexmedetomidine, High Dose | Dexmedetomidine 1.2 µg/kg per hour administered for a maximum duration of five days Dexmedetomidine: Dexmedetomidine at 0.4 or 1.2 µg/kg per hour is administered for a maximum duration of five days |
| FG002 | Placebo | Normal saline Placebo: Normal saline for five days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Dexmedetomidine, Low Dose | Dexmedetomidine 0.4 µg/kg per hour administered for a maximum duration of five days Dexmedetomidine: Dexmedetomidine at 0.4 or 1.2 µg/kg per hour is administered for a maximum duration of five days |
| BG001 | Dexmedetomidine, High Dose |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Cumulative Lorazepam Dose Over the First Seven Days of Alcohol Withdrawal | Posted | Median | Inter-Quartile Range | mg | Seven days |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dexmedetomidine, Low Dose | Dexmedetomidine 0.4 µg/kg per hour administered for a maximum duration of five days Dexmedetomidine: Dexmedetomidine at 0.4 or 1.2 µg/kg per hour is administered for a maximum duration of five days |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypotension | Cardiac disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Robert MacLaren | University of Colorado | 303 724-2622 | rob.maclaren@ucdenver.edu |
Not provided
| ID | Term |
|---|---|
| D020927 | Dexmedetomidine |
| ID | Term |
|---|---|
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Placebo | Other | Normal saline for five days. |
|
| Every 2-4 hours for 24 hours after starting study drug |
| The Occurrence of Adverse Events. | Occurrence of hypotension or bradycardia while on study drug | Seven days |
| Plasma Epinephrine Concentrations Across Groups Over Time | Plasma epinephrine concentrations | Four days with samples measured prior to study drug and 48 and 96 hours after starting study drug |
| Duration of Study Drug Administration | The duration of study drug in hours as measured when the subject was discharged from the ICU, for up to 24 weeks |
| ICU Length of Stay | The duration of ICU stay in days as measured at time of hospital discharge, for up to 24 weeks |
Dexmedetomidine 1.2 µg/kg per hour administered for a maximum duration of five days Dexmedetomidine: Dexmedetomidine at 0.4 or 1.2 µg/kg per hour is administered for a maximum duration of five days |
| BG002 | Placebo | Normal saline Placebo: Normal saline for five days. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Weight | Mean | Full Range | kg |
|
| Acute Physiologic And Chronic Health Evaluation (APACHE) III | APACHE III measures the severity of disease for adult patients admitted to intensive care units. The point score is calculated as a summation from scores assigned to a patient's age, primary comorbidity, preexisting comorbidities, location prior to ICU admission, Glasgow Coma Scale, and 20 routine physiological measurements. APACHE III scores range from 0 to 299. This provides an initial risk classification of severely ill hospitalized patients in defined groups with higher scores indicating greater disease severity and correlated to higher mortality risk. | Mean | Inter-Quartile Range | units on a scale |
|
| Endotracheal Intubation at Study Entry | Number | participants |
|
| Child-Pugh Score | The Child-Pugh score is used to assess the prognosis of chronic liver disease. The point score is calculated from the summation of points assigned for total bilirubin (serum), albumin (serum), prothrombin time, and the presence of ascites and encephalopathy. The range is from 0 to 15. Grade A liver disease (scores of 5-6) predict two-year survival of 85%. Grade B liver disease (scores of 7-9) predict two-year survival of 55%. Grade C liver disease (scores of 10-15) predict two-year survival of 35%. | Mean | Full Range | units on a scale |
|
| Lorazepam requirement 24 Hour Prior to Study Entry | Mean | Inter-Quartile Range | mg |
|
| Time from Study Qualification to Study Drug Start | Median | Inter-Quartile Range | hours |
|
| Placebo |
Normal saline Placebo: Normal saline for five days. |
|
|
|
| Primary | Change in 12-Hour Lorazepam Requirement Pre- and Post-Treatment | Posted | Median | Inter-Quartile Range | mg | 12 hours before treatment, 12 hours after treatment on first day of starting study drug |
|
|
|
|
| Primary | Change in 24-Hour Lorazepam Requirement Pre- and Post-Treatment | Posted | Median | Inter-Quartile Range | mg | 24 hours before treatment, 24 hours after treatment on first day of starting study drug |
|
|
|
|
| Secondary | The Degree of Alcohol Withdrawal Assessed by Clinical Institute Withdrawal Assessment (CIWA) Scores | Proportion of clinical institute withdrawal assessment (CIWA) Scores listed as severe or moderate 24 Hours after Starting Study Drug. All subjects had at least four CIWA assessments.The CIWA is a ten item scale with each item on the scale scored independently on a 0-7 or 0-4 scale, and the summation of the scores yielding an aggregate value that correlates to the severity of alcohol withdrawal. Ranges of scores are from 0 to 67. Mild alcohol withdrawal is defined with a score less than or equal to 15, moderate with scores of 16 to 20, and severe with any score greater than 20. The ten items evaluated include nausea and vomiting, tremor, sweats, anxiety, agitation, tactile disturbances, auditory disturbances, visual disturbances, headache, and orientation. | Posted | Number | percentage of ciwa assessment | Every 2-4 hours for 24 hours after starting study drug |
|
|
|
|
| Secondary | The Occurrence of Adverse Events. | Occurrence of hypotension or bradycardia while on study drug | Posted | Number | participants | Seven days |
|
|
|
|
| Secondary | Plasma Epinephrine Concentrations Across Groups Over Time | Plasma epinephrine concentrations | Posted | Mean | Standard Deviation | ng/mL | Four days with samples measured prior to study drug and 48 and 96 hours after starting study drug |
|
|
|
|
| Secondary | Duration of Study Drug Administration | Posted | Median | Inter-Quartile Range | hours | The duration of study drug in hours as measured when the subject was discharged from the ICU, for up to 24 weeks |
|
|
|
|
| Secondary | ICU Length of Stay | Posted | Median | Inter-Quartile Range | days | The duration of ICU stay in days as measured at time of hospital discharge, for up to 24 weeks |
|
|
|
|
| 0 |
| 8 |
| 4 |
| 8 |
| EG001 | Dexmedetomidine, High Dose | Dexmedetomidine 1.2 µg/kg per hour administered for a maximum duration of five days Dexmedetomidine: Dexmedetomidine at 0.4 or 1.2 µg/kg per hour is administered for a maximum duration of five days | 0 | 8 | 3 | 8 |
| EG002 | Placebo | Normal saline Placebo: Normal saline for five days. | 0 | 8 | 2 | 8 |
| Bradycardia | Cardiac disorders |
|
| Hypertension | Cardiac disorders |
|
Not provided
Not provided
| No |
| Superiority or Other |
| No |
| Superiority or Other |
| Title | Measurements |
|---|---|
|
| 0.35 |
Percentage of CIWA scores rates as severe |
| No |
| Superiority or Other |
| Title | Measurements |
|---|---|
|
| 0.47 |
| No |
| Superiority or Other |
| For bradycardia | Fisher Exact | 1 | No | Superiority or Other |
| For bradycardia | Fisher Exact | 0.2 | No | Superiority or Other |
|
| Time 96 hours |
|
| No |
| Superiority or Other |
| No |
| Superiority or Other |