As part of routine care, the bedside nurse will record the administration of all sedative agents. The hourly, daily and cumulative doses of agents will be determined by the sum of as needed doses, scheduled intermittent doses, and hourly infusion rates. All conventional therapies will be guided by the institution-specific, symptom-triggered alcohol withdrawal protocol to maintain CIWA scores ≤ 7. Intravenous lorazepam is the preferred benzodiazepine for management of alcohol withdrawal in the medical ICU. Phenobarbital and propofol are infrequently used and they are not included in the protocol. All benzodiazepine and barbiturate doses, whether oral or intravenous, will be converted to lorazepam equivalents using the following conversion: 1 mg lorazepam = 2 mg midazolam = 7.5 mg clorazepate = 15 mg phenobarbital.
Ketamine vs. Placebo as Adjunctive Therapies for Severe Alcohol Withdrawal
Brief Summary
Intervention / Treatment
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Ketamine (DRUG)Blinded study drug administered to experimental arm
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Dexmedetomidine (DRUG)Open-label study drug administered to both arms
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Normal saline (DRUG)Blinded comparator administered to control arm
Condition or Disease
- Alcohol Withdrawal
Phase
Study Design
| Study type: | INTERVENTIONAL |
|---|---|
| Status: | Withdrawn |
| Study results: | No Results Available |
| Age: | 18 Years to 85 Years |
| Enrollment: | 0 (ACTUAL) |
| Funded by: | Other |
| Allocation: | Randomized |
| Primary Purpose: | Treatment |
MaskingQUADRUPLE:
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Clinical Trial Dates
| Start date: | Feb 01, 2018 | ESTIMATED |
|---|---|---|
| Primary Completion: | Dec 01, 2018 | ESTIMATED |
| Completion Date: | Dec 01, 2018 | ESTIMATED |
| Study First Posted: | Jul 06, 2016 | ESTIMATED |
| Results First Posted: | Aug 31, 2020 | |
| Last Updated: | Jan 17, 2018 |
Sponsors / Collaborators
Location
The objectives of this randomized, double-blind pilot study of 20 subjects with severe alcohol withdrawal are to a) determine if adding ketamine 0.5 mg/kg per hour to dexmedetomidine 0.6 µg/kg per hour (both agents administered for up to 72 hours) as adjunctive therapies to a symptom-triggered benzodiazepine protocol reduces the dose requirements of conventional sedatives while maintaining patient comfort and safety; and to b) explore whether epinephrine, a marker of autonomic activity, is expressed differently when ketamine is added to dexmedetomidine as adjunctive therapies.
Participant Groups
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Ketamine 0.25 mg/kg bolus followed by 0.5 mg/kg per hour AND Dexmedetomidine by continuous infusion at a fixed rate of 0.6 µg/kg per hour, both administered for up to 72 hours
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Normal saline, as a 500 mL infusion bag, to represent placebo AND Dexmedetomidine by continuous infusion at a fixed rate of 0.6 µg/kg per hour, both administered for up to 72 hours
Eligibility Criteria
| Sex: | All |
|---|---|
| Minimum Age: | 18 |
| Maximum Age: | 85 |
| Age Groups: | Adult / Older Adult |
| Healthy Volunteers: | Yes |
1. Severe alcohol withdrawal defined by a CIWA score ≥ 15 and the need for at least 16 mg of lorazepam equivalents over a four-hour period. All benzodiazepine and barbiturate doses, whether oral or intravenous, will contribute to the cumulative amount using the following conversion: 1 mg lorazepam = 2 mg midazolam = 7.5 mg clorazepate = 15 mg phenobarbital.
2. Patients receiving standard therapy for severe alcohol withdrawal according to the UCH-specific, symptom-triggered alcohol withdrawal protocol in the ICU (or admission to the ICU is anticipated). Lorazepam is the preferred benzodiazepine agent for patients requiring ICU admission due to alcohol withdrawal.
3. Informed consent within 36 hours of qualifying for the study.
Exclusion Criteria:
1. Patients \< 18 years of age or \> 85 years of age.
2. Patients receiving benzodiazepine therapy for purposes other than alcohol withdrawal (e.g. sedation, seizure control other than alcohol withdrawal).
3. Patients with alcohol withdrawal not requiring ICU admission.
4. Patients receiving epidural administration of medication(s).
5. Comatose patients by metabolic or neurologic affectation.
6. Patients with active myocardial ischemia or second- or third-degree heart block.
7. Patients with Child-Pugh score of C.
8. Moribund state with planned withdrawal of life support.
9. Patient pending transfer to another facility.
10. Patients with known or suspected severe adverse reactions to dexmedetomidine (or clonidine) or ketamine.
11. Pregnant females or females suspected of being pregnant.
12. Prisoners or active parolees.
13. Previous study participation.
14. Patients already receiving ketamine for alcohol withdrawal. Patients receiving dexmedetomidine will be excluded if the infusion exceeds 1 µg/kg per hour for more than two hours or any rate for a cumulative duration of 12 hours.
Primary Outcomes
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As part of routine care, the bedside nurse will record the administration of all sedative agents. The hourly, daily and cumulative doses of agents will be determined by the sum of as needed doses, scheduled intermittent doses, and hourly infusion rates. All conventional therapies will be guided by the institution-specific, symptom-triggered alcohol withdrawal protocol to maintain CIWA scores ≤ 7. Intravenous lorazepam is the preferred benzodiazepine for management of alcohol withdrawal in the medical ICU. Phenobarbital and propofol are infrequently used and they are not included in the protocol. All benzodiazepine and barbiturate doses, whether oral or intravenous, will be converted to lorazepam equivalents using the following conversion: 1 mg lorazepam = 2 mg midazolam = 7.5 mg clorazepate = 15 mg phenobarbital.
-
As part of routine care, the bedside nurse will record the administration of all sedative agents. The hourly, daily and cumulative doses of agents will be determined by the sum of as needed doses, scheduled intermittent doses, and hourly infusion rates. All conventional therapies will be guided by the institution-specific, symptom-triggered alcohol withdrawal protocol to maintain CIWA scores ≤ 7. Intravenous lorazepam is the preferred benzodiazepine for management of alcohol withdrawal in the medical ICU. Phenobarbital and propofol are infrequently used and they are not included in the protocol. All benzodiazepine and barbiturate doses, whether oral or intravenous, will be converted to lorazepam equivalents using the following conversion: 1 mg lorazepam = 2 mg midazolam = 7.5 mg clorazepate = 15 mg phenobarbital.
Secondary Outcomes
-
As part of routine care, the bedside nurse will record the administration of all sedative agents. The hourly, daily and cumulative doses of agents will be determined by the sum of as needed doses, scheduled intermittent doses, and hourly infusion rates. All conventional therapies will be guided by the institution-specific, symptom-triggered alcohol withdrawal protocol to maintain CIWA scores ≤ 7. Intravenous lorazepam is the preferred benzodiazepine for management of alcohol withdrawal in the medical ICU. Phenobarbital and propofol are infrequently used and they are not included in the protocol. All benzodiazepine and barbiturate doses, whether oral or intravenous, will be converted to lorazepam equivalents using the following conversion: 1 mg lorazepam = 2 mg midazolam = 7.5 mg clorazepate = 15 mg phenobarbital.
-
As part of routine care, the bedside nurse will record the administration of all sedative agents. The hourly, daily and cumulative doses of agents will be determined by the sum of as needed doses, scheduled intermittent doses, and hourly infusion rates. All conventional therapies will be guided by the institution-specific, symptom-triggered alcohol withdrawal protocol to maintain CIWA scores ≤ 7. Intravenous lorazepam is the preferred benzodiazepine for management of alcohol withdrawal in the medical ICU. Phenobarbital and propofol are infrequently used and they are not included in the protocol. All benzodiazepine and barbiturate doses, whether oral or intravenous, will be converted to lorazepam equivalents using the following conversion: 1 mg lorazepam = 2 mg midazolam = 7.5 mg clorazepate = 15 mg phenobarbital.
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CIWA scores will be assessed hourly by the bedside nurse. The proportion of CIWA scores ≥ 15 (severe withdrawal symptoms), 8 - 14 (moderate withdrawal symptoms), and ≤ 7 (minimal withdrawal symptoms) will be determined.
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Blood pressure and heart rate will be assessed hourly by the bedside nurse. Hypotension will be defined as a systolic blood pressure ≤ 90 mmHg or a decrease of systolic blood pressure of 40 mmHg, hypertension will be defined as a systolic blood pressure ≥ 180 mmHg or an increase of systolic blood pressure of 40 mmHg, bradycardia will be defined as a heart rate ≤ 55 beats/minute or a decrease of 20 beats/minutes, and tachycardia will be defined as a heart rate ≥ 120 beats/minute or an increase of 20 beats/minutes. Highest and lowest daily measurements of each will also be collected.
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Plasma epinephrine concentrations will be assessed prior to study drug and at times 24, 48, 72 and 96 hours after initiating study drug
More Details
| NCT Number: | NCT02823977 |
|---|---|
| Other IDs: | 16-1303 |
| Study URL: | https://clinicaltrials.gov/study/NCT02823977 |