NCT02823977

Brief Summary

This study is designed to evaluate the addition of ketamine to dexmedetomidine as adjunctive therapies of severe alcohol withdrawal in medical ICU patients. Specifically, this study will assess whether the combination of ketamine and dexmedetomidine reduces the doses of conventional agents used for alcohol withdrawal while maintaining patient comfort and safety and will explore if the combination alters the expression of catecholamines in the serum over time.

Trial Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Feb 2018

Shorter than P25 for phase_4

Geographic Reach
1 country

1 active site

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 1, 2016

Completed
5 days until next milestone

First Posted

Study publicly available on registry

July 6, 2016

Completed
1.6 years until next milestone

Study Start

First participant enrolled

February 1, 2018

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2018

Completed
Last Updated

January 19, 2018

Status Verified

January 1, 2018

Enrollment Period

10 months

First QC Date

July 1, 2016

Last Update Submit

January 17, 2018

Conditions

Alcohol Withdrawal

Keywords

ketaminedexmedetomidinealcohol

Outcome Measures

Primary Outcomes (3)

  • Cumulative Lorazepam Dose Over the First 12 Hours of Alcohol Withdrawal

    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.

    12 hours

  • Cumulative Lorazepam Dose Over the First 24 Hours of Alcohol Withdrawal

    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.

    24 hours

  • Cumulative Lorazepam Dose Over the 72 Hours of Alcohol Withdrawal

    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.

    72 hours

Secondary Outcomes (5)

  • 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

  • The Degree of Alcohol Withdrawal Assessed by Clinical Institute Withdrawal Assessment (CIWA) Scores

    72 hours

  • The Occurrence of Adverse Events: hypotension, hypertension, bradycardia, tachycardia

    72 hours

  • Plasma Epinephrine Concentrations Across Groups Over Time

    96 hours

Study Arms (2)

Ketamine / Dexmedetomidine

EXPERIMENTAL

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

Drug: KetamineDrug: Dexmedetomidine

Placebo / Dexmedetomidine

PLACEBO COMPARATOR

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

Drug: DexmedetomidineDrug: Normal saline

Interventions

KetamineDRUG

Blinded study drug administered to experimental arm

Also known as: Ketalar
Ketamine / Dexmedetomidine
DexmedetomidineDRUG

Open-label study drug administered to both arms

Also known as: Precedex
Ketamine / DexmedetomidinePlacebo / Dexmedetomidine
Normal salineDRUG

Blinded comparator administered to control arm

Also known as: 0.9% NaCl in water
Placebo / Dexmedetomidine

Eligibility Criteria

Age18 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • 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.
  • Informed consent within 36 hours of qualifying for the study.

You may not qualify if:

  • Patients \< 18 years of age or \> 85 years of age.
  • Patients receiving benzodiazepine therapy for purposes other than alcohol withdrawal (e.g. sedation, seizure control other than alcohol withdrawal).
  • Patients with alcohol withdrawal not requiring ICU admission.
  • Patients receiving epidural administration of medication(s).
  • Comatose patients by metabolic or neurologic affectation.
  • Patients with active myocardial ischemia or second- or third-degree heart block.
  • Patients with Child-Pugh score of C.
  • Moribund state with planned withdrawal of life support.
  • Patient pending transfer to another facility.
  • Patients with known or suspected severe adverse reactions to dexmedetomidine (or clonidine) or ketamine.
  • Pregnant females or females suspected of being pregnant.
  • Prisoners or active parolees.
  • Previous study participation.
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Colorado Hospital

Aurora, Colorado, 80010, United States

Location

MeSH Terms

Interventions

KetamineDexmedetomidineSaline SolutionWater

Intervention Hierarchy (Ancestors)

CyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsImidazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsCrystalloid SolutionsIsotonic SolutionsSolutionsPharmaceutical PreparationsHydroxidesAlkaliesInorganic ChemicalsAnionsIonsElectrolytesOxidesOxygen Compounds

Study Officials

  • Robert MacLaren, PharmD, MPH

    University of Colorado, Denver

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 1, 2016

First Posted

July 6, 2016

Study Start

February 1, 2018

Primary Completion

December 1, 2018

Study Completion

December 1, 2018

Last Updated

January 19, 2018

Record last verified: 2018-01

Data Sharing

IPD Sharing
Will not share

Aggregate data will be presented and published in a peer reviewed journal. Individual data will not be shared.

Locations

US(1)