PKAT: Alcohol Withdrawal Syndrome Treated With Adjunctive Phenobarbital or Ketamine

Sponsor

Santa Barbara Cottage Hospital (Other)

Overall Status

Withdrawn

CT.gov ID

NCT03788889

Collaborator

(none)

Enrollment

Arms

Study Details

Study Description

Brief Summary

The goal of this study will aim to determine if adding phenobarbital or ketamine to a symptom-triggered benzodiazepine regimen decreases the rate of intensive care unit admissions during the treatment of alcohol withdrawal syndrome when compared to symptom-triggered benzodiazepine therapy alone.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Withdrawal Syndrome	Drug: Ketamine Drug: Phenobarbital Drug: Lorazepam Drug: Placebo A Drug: Placebo B	Phase 4

Detailed Description

The primary objective of this study is to compare phenobarbital and ketamine adjunctive therapies to lorazepam-based therapy in the treatment of acute alcohol withdrawal syndrome.

It is hypothesized that the use of an alternative agent, either phenobarbital or ketamine, when used as an adjunct to symptom-triggered lorazepam therapy will significantly reduce the rate of intensive care unit admissions and thereby reduce the total cost associated with hospital admission for treatment of alcohol withdrawal syndrome.

Enrolled patients will be admitted to Santa Barbara Cottage Hospital where they will be monitored with continuous pulse oximetry and cardiac telemetry. They will remain hospitalized while undergoing study-guided therapy in addition to supportive care for acute alcohol withdrawal syndrome. Patients will undergo standard of care therapy with lorazepam symptom-triggered therapy regardless of study participation.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

prospective, randomized control trialprospective, randomized control trial

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

Each participant will be randomized according to a web-based randomization program employed by a research pharmacist once the Emergency Department provider deems the patient appropriate for inpatient treatment of alcohol withdrawal syndrome. Each medication will be packaged by Santa Barbara Cottage Hospital pharmacy. In order to blind both the clinicians and the participants, the pharmacy will provide medication bags that are identical. Therefore, Emergency Department nursing staff and physicians will be unaware of which study drug is being provided to the patient. Normal saline will be used as a placebo to mimic study drugs (phenobarbital and ketamine). Pharmacy will remain unblinded and maintain records of which treatment assignment is prepared for each patient. Treatment will be provided for the duration of the patient's hospitalization; therefore, treatment compliance will be documented in the electronic health record using the medication bag identifier.

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-Blinded, Placebo-Controlled Study Evaluating Phenobarbital and Ketamine Adjunctive Therapies in the Treatment of Alcohol Withdrawal Syndrome

Anticipated Study Start Date :

Apr 12, 2019

Actual Primary Completion Date :

Apr 12, 2019

Actual Study Completion Date :

Apr 12, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Lorazepam + Ketamine + Placebo A Ketamine - infusion (0.15 - 0.4 mg/kg/hr) and placebo injections titrated by increases of 0.075 mg/kg/hr every 30 minutes for Clinical Institute Withdrawal Assessment for Alcohol (revised version) (CIWA-Ar) greater than or equal to 10 in addition to lorazepam symptom-triggered therapy Ketamine dosing will be based on ideal body weight Ketamine infusion will be discontinued once CIWA-Ar less than 10 for 4 hours	Drug: Ketamine Ketamine infusion Other Names: Ketalar Drug: Lorazepam Standard of Care Other Names: Ativan Drug: Placebo A Placebo injection Other Names: Normal saline
Active Comparator: Lorazepam + Phenobarbital + Placebo B Phenobarbital - IV push (260 mg loading followed by 130 mg q1 hour) with placebo infusion until CIWA-Ar less than 10 with a maximum daily dose of 10mg/kg in addition to lorazepam symptom-triggered dosing for recurrent symptoms (Gold 2007) Maximum daily dose will be used in order to prevent over sedation as well as provide adequate storage in pharmacy monitored refrigerators for study drugs	Drug: Phenobarbital Phenobarbital intravenous injection Other Names: Solfoton, Luminal Drug: Lorazepam Standard of Care Other Names: Ativan Drug: Placebo B Placebo infusion Other Names: Normal saline
Placebo Comparator: Lorazepam + Placebo A + Placebo B Lorazepam will be administered every 30 minutes as indicated based on CIWA-Ar protocol for Cottage Health in addition to placebo injections and placebo infusion	Drug: Lorazepam Standard of Care Other Names: Ativan Drug: Placebo A Placebo injection Other Names: Normal saline Drug: Placebo B Placebo infusion Other Names: Normal saline

Arm

Intervention/Treatment

Active Comparator: Lorazepam + Ketamine + Placebo A

Ketamine - infusion (0.15 - 0.4 mg/kg/hr) and placebo injections titrated by increases of 0.075 mg/kg/hr every 30 minutes for Clinical Institute Withdrawal Assessment for Alcohol (revised version) (CIWA-Ar) greater than or equal to 10 in addition to lorazepam symptom-triggered therapy Ketamine dosing will be based on ideal body weight Ketamine infusion will be discontinued once CIWA-Ar less than 10 for 4 hours

Drug: Ketamine

Ketamine infusion

Other Names:

Ketalar

Drug: Lorazepam

Standard of Care

Other Names:

Ativan

Drug: Placebo A

Placebo injection

Other Names:

Normal saline

Active Comparator: Lorazepam + Phenobarbital + Placebo B

Phenobarbital - IV push (260 mg loading followed by 130 mg q1 hour) with placebo infusion until CIWA-Ar less than 10 with a maximum daily dose of 10mg/kg in addition to lorazepam symptom-triggered dosing for recurrent symptoms (Gold 2007) Maximum daily dose will be used in order to prevent over sedation as well as provide adequate storage in pharmacy monitored refrigerators for study drugs

Drug: Phenobarbital

Phenobarbital intravenous injection

Other Names:

Solfoton, Luminal

Drug: Lorazepam

Standard of Care

Other Names:

Ativan

Drug: Placebo B

Placebo infusion

Other Names:

Normal saline

Placebo Comparator: Lorazepam + Placebo A + Placebo B

Lorazepam will be administered every 30 minutes as indicated based on CIWA-Ar protocol for Cottage Health in addition to placebo injections and placebo infusion

Drug: Lorazepam

Standard of Care

Other Names:

Ativan

Drug: Placebo A

Placebo injection

Other Names:

Normal saline

Drug: Placebo B

Placebo infusion

Other Names:

Normal saline

Outcome Measures

Primary Outcome Measures

Intensive Care Unit admission rate [Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years]
Number of admissions to the intensive care unit

Secondary Outcome Measures

Incidence of withdrawal seizures [Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years]
Number of patients with documented seizures while treated for alcohol withdrawal syndrome
Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) scores [Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years]
CIWA-Ar scores (initial, maximum, discharge); Total score is cumulative of subscale measures: Minimum score is 0 (no evidence of alcohol withdrawal), Maximum score is 67 (severe alcohol withdrawal) Subscale measures: A) Nausea and vomiting (score 0-7); B) Tremor (score 0-7); C) Paroxysmal sweats (score 0-7); D) Anxiety (score 0-7); E) Tactile disturbances (score 0-7); F) Auditory disturbances (score 0-7); G) Visual disturbances (score 0-7); H) Headache, fullness in head (score 0-7); I) Agitation (score 0-7); J) Orientation and clouding of sensorium (score 0-4)
Cumulative dose of medication/s administered [Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years]
Cumulative dose of Lorazepam, Ketamine, and Phenobarbital
Incidence of refractory alcohol withdrawal requiring alternative sedation with dexmedetomidine, propofol or midazolam infusions [Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years]
Number of patients who require Dexmedetomidine, Propofol or Benzodiazepine continuous infusions and average dose while being treated for alcohol withdrawal syndrome
Rate of mechanical ventilation [Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years]
Rate of intubation
Incidence of alcohol withdrawal hallucinations [Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years]
Number of patients with documented auditory or visual hallucinations

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Primary admitting diagnosis of acute alcohol withdrawal syndrome based on International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10), code F10.3, F10.4.