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Assessment of Valproate on Ethanol Withdrawal (PAVE)

Primary Purpose

Alcohol Dependence, Alcohol Withdrawal Syndrome, Trauma

Status
Unknown status
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Valproate
Lorazepam
Sponsored by
CAMC Health System
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Alcohol Dependence focused on measuring alcohol withdrawal syndrome, trauma, alcohol use disorder, alcohol, lorazepam, benzodiazepine, valproate

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Admission to Trauma Services
  • Heavy drinkers based on social history

    • Men <65 years: > 4 drinks per day or 14 per week
    • Women: > 3 drinks per day or 7 drinks per week
    • All adults >65 years: > 3 drinks per day or 7 drinks per week
  • Moderate or severe alcohol use disorder based on social history and DSM-5 criteria

    • Moderate: Presence of 4-5 symptoms based on social history
    • Severe: Presence of 6 symptoms based on social history

Exclusion Criteria:

  • Intubated patients
  • Glasgow Coma Score <8
  • Grade IV liver laceration or greater
  • Child-Pugh Class B or greater, history of cirrhosis, or cirrhosis identified by radiographic imaging upon admission
  • Transaminase (AST/ALT) elevation of ≥ 2x normal
  • Anticipated admission less than 72 hours
  • Levetiracetam administration for seizure prophylaxis secondary to a traumatic brain injury
  • Patient with VPA as home medication
  • Known allergy to VPA
  • Patients with pre-existing blood dyscrasias, i.e. thrombocytopenia (platelet count < 50,000, etc)
  • Inability to obtain social history from patient, surrogate, family member or an individual deemed to be knowledgeable about the patient's social history
  • Pregnancy

Sites / Locations

  • Charleston Area Medical Center, General Hospital, Level 1 Trauma CenterRecruiting
  • Charleston Area Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

CIWA Protocol/BZD and Valproate

CIWA Protocol Only

Arm Description

Interventions to decrease symptoms of AWS will be made based on the CIWA tool. CIWA Score 9-14: 1 mg IV push lorazepam CIWA Score >15: 2 mg IV push lorazepam Patients who have a known history of alcohol withdrawal seizures or who have received greater than 4 mg IV lorazepam per CIWA protocol will be placed on a scheduled lorazepam regimen, 1 mg every 6 hours. The primary managing service may increase the scheduled lorazepam regimen above 1mg every 6 hours if needed to control withdrawal symptoms. Scheduled lorazepam will be discontinued or de-escalated following a 24-hour period in which no additional lorazepam was received per CIWA protocol. The treatment group will also receive scheduled valproate (VPA), 15 mg/kg divided over 4 doses, rounded up to the nearest increment of 50mg (i.e. a 70 kg person would be administered 300 mg IV VPA every 6 hours) for 96 hours.

Interventions to decrease symptoms of AWS will be made based on the CIWA tool CIWA Score 9-14: 1 mg IV push lorazepam CIWA Score >15: 2 mg IV push lorazepam Patients who have a known history of alcohol withdrawal seizures or who have received greater than 4 mg IV lorazepam per CIWA protocol will be placed on a scheduled lorazepam regimen, 1 mg every 6 hours. The primary managing service may increase the scheduled lorazepam regimen above 1mg every 6 hours if needed to control withdrawal symptoms. Scheduled lorazepam will be discontinued or de-escalated following a 24-hour period in which no additional lorazepam was received per CIWA protocol.

Outcomes

Primary Outcome Measures

Lorazepam use in patient monitored with CIWA
Amount of lorazepam administration in response to CIWA score

Secondary Outcome Measures

CIWA score
CIWA is a ten item scale used in the assessment and management of alcohol withdrawal.
Hospital Length of Stay
Date of admission to date of discharge from the hospital
Intensive Care Unit Length of Stay
Date of admission to date of discharge from the Intensive Care Unit
In-hospital Mortality
Number of deaths
Valproate associated side effects
Known side effects associated with valproate use, such as thrombocytopenia, transaminitis, pancreatitis, and hyperammonemia

Full Information

First Posted
July 14, 2017
Last Updated
July 27, 2017
Sponsor
CAMC Health System
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1. Study Identification

Unique Protocol Identification Number
NCT03235531
Brief Title
Assessment of Valproate on Ethanol Withdrawal
Acronym
PAVE
Official Title
Prospective Assessment of Valproate on Ethanol Withdrawal
Study Type
Interventional

2. Study Status

Record Verification Date
July 2017
Overall Recruitment Status
Unknown status
Study Start Date
July 11, 2017 (Actual)
Primary Completion Date
July 11, 2019 (Anticipated)
Study Completion Date
January 1, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
CAMC Health System

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
Alcohol use disorder, or heavy drinking, is commonly seen in patients who present to trauma centers. These patients are at risk for Alcohol Withdrawal Syndrome (AWS), which is collection of symptoms that can range from anxiety and restlessness to seizures, delirium and even death. The Clinical Institute Withdrawal Assessment (CIWA) tool is routinely used to assess alcohol withdrawal symptoms. Benzodiazepines (BZD) are commonly administered to trauma patients who exhibit symptoms of AWS based on the CIWA scoring system. Although these medications have proven efficacy, they can also have negative side effects which may affect recovery. Valprate (VPA) is a medication which may have efficacy in management of AWS symptoms, thus ameliorating or preventing the need for BZD administration. This trial will study the effectiveness of VPA in the prevention of AWS symptoms by comparing the amount of BZD use in trauma patients who receive BZD treatment as indicated by CIWA scores with patients who receive prophylactic VPA therapy in addition to BZD as indicated by CIWA scores.
Detailed Description
Alcohol use disorder is a common comorbidity among trauma patients. This pre-existing condition is associated with Alcohol Withdrawal Syndrome (AWS) and frequently complicates the management of this patient population. Current treatment and/or prevention of AWS includes the administration of sedatives (benzodiazepines [BZD]) in response to the manifestation AWS symptoms. This manifestation is indicated by monitoring patients using the Clinical Institute Withdrawal Assessment (CIWA) tool. Benzodiazepines elicit an effect on AWS via mediation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Benzodiazepines, however, have the potential to promote multiple negative effects in the acute care setting, including increased incidence of delirium, hospital stay, mortality, and the potential for decreased long-term cognitive function. The antiepileptic medication valproate (VPA) also has GABA activity in the brain, but may be less likely to promote the negative effects associated with BZDs. Currently, previous experience with this agent for the prevention of AWS is limited to two small studies. In these studies VPA was shown to decrease symptoms of AWS as indicated by patients' CIWA scores. Therefore, VPA could serve as an efficacious adjuvant therapy for the prevention of AWS. The aim of this study is to determine whether VPA will decrease the use of BZD in patients who are receiving symptom-based preventative therapy via CIWA monitoring. The hypothesis is that VPA will decrease the utilization of symptom-based lorazepam administration in patients who are determined to be at risk of alcohol withdrawal due to routine consumption of alcohol. The purpose of this study is to determine if prophylactic VPA for the prevention of alcohol withdrawal syndrome can decrease symptom-triggered use of benzodiazepines in patients monitored for alcohol withdrawal syndrome with the CIWA. The Primary objective of this study is to determine if prophylactic VPA acid is associated with decreased lorazepam use in patients monitored for alcohol withdrawal syndrome with the CIWA. Secondary objectives are: To evaluate the difference between comparator arms with respect to: CIWA scores between patients with and without VPA prophylaxis Hospital and Intensive Care Unit (ICU) length of stay In-hospital mortality VPA acid associated side effects (e.g. thrombocytopenia, transaminitis, pancreatitis) This will be single-center prospective, randomized study, enrolling trauma patients with a history of alcohol consumption admitted to a Level 1 trauma center. Patients included in this study will receive standard therapies for AWS practiced at study institution which include monitoring of withdrawal symptoms and the administration of BZDs (lorazepam) based on CIWA monitoring. Following informed consent, patients will be randomized to receive CIWA protocol monitoring/BZD or CIWA protocol monitoring/BZD and VPA. Therefore, patients that meet the inclusion criteria will be separated into two study groups to compare outcomes: Treatment Group: Patients treated with CIWA protocol/BZD and VPA Control Group: Patients treated with CIWA protocol/BZD only.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol Dependence, Alcohol Withdrawal Syndrome, Trauma, Heavy Drinking, Alcohol Use Disorder
Keywords
alcohol withdrawal syndrome, trauma, alcohol use disorder, alcohol, lorazepam, benzodiazepine, valproate

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
210 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CIWA Protocol/BZD and Valproate
Arm Type
Experimental
Arm Description
Interventions to decrease symptoms of AWS will be made based on the CIWA tool. CIWA Score 9-14: 1 mg IV push lorazepam CIWA Score >15: 2 mg IV push lorazepam Patients who have a known history of alcohol withdrawal seizures or who have received greater than 4 mg IV lorazepam per CIWA protocol will be placed on a scheduled lorazepam regimen, 1 mg every 6 hours. The primary managing service may increase the scheduled lorazepam regimen above 1mg every 6 hours if needed to control withdrawal symptoms. Scheduled lorazepam will be discontinued or de-escalated following a 24-hour period in which no additional lorazepam was received per CIWA protocol. The treatment group will also receive scheduled valproate (VPA), 15 mg/kg divided over 4 doses, rounded up to the nearest increment of 50mg (i.e. a 70 kg person would be administered 300 mg IV VPA every 6 hours) for 96 hours.
Arm Title
CIWA Protocol Only
Arm Type
Active Comparator
Arm Description
Interventions to decrease symptoms of AWS will be made based on the CIWA tool CIWA Score 9-14: 1 mg IV push lorazepam CIWA Score >15: 2 mg IV push lorazepam Patients who have a known history of alcohol withdrawal seizures or who have received greater than 4 mg IV lorazepam per CIWA protocol will be placed on a scheduled lorazepam regimen, 1 mg every 6 hours. The primary managing service may increase the scheduled lorazepam regimen above 1mg every 6 hours if needed to control withdrawal symptoms. Scheduled lorazepam will be discontinued or de-escalated following a 24-hour period in which no additional lorazepam was received per CIWA protocol.
Intervention Type
Drug
Intervention Name(s)
Valproate
Intervention Description
Valproate is an anti-epileptic medication that can influence the chemical changes in the brain that result from alcohol withdrawal syndrome (AWS) via three mechanisms of action: (1) an increase in GABA activity, (2) inhibition of glutamate binding to NMDA, and (3) restoration of the balance between dopamine and acetylcholine activity. VPA may be effective in the prevention of AWS, and could serve as efficacious adjuvant to traditional benzodiazepine (BZD) therapy for AWS, both decreasing symptoms of AWS and decreasing the use of BZDs.
Intervention Type
Drug
Intervention Name(s)
Lorazepam
Intervention Description
Lorazepam is a benzodiazepine used to treat symptoms of AWS. Standard of care at CAMC is monitoring by CIWA tool and administration of lorazepam according to CIWA score.
Primary Outcome Measure Information:
Title
Lorazepam use in patient monitored with CIWA
Description
Amount of lorazepam administration in response to CIWA score
Time Frame
Time between CIWA initiation and discontinuation for up to 3 weeks
Secondary Outcome Measure Information:
Title
CIWA score
Description
CIWA is a ten item scale used in the assessment and management of alcohol withdrawal.
Time Frame
During patient hospital stay for up to 6 months
Title
Hospital Length of Stay
Description
Date of admission to date of discharge from the hospital
Time Frame
During patient hospital stay for up to 6 months
Title
Intensive Care Unit Length of Stay
Description
Date of admission to date of discharge from the Intensive Care Unit
Time Frame
During patient Intensive Care Unit stay for up to 6 months
Title
In-hospital Mortality
Description
Number of deaths
Time Frame
During patient hospital stay for up to 6 months
Title
Valproate associated side effects
Description
Known side effects associated with valproate use, such as thrombocytopenia, transaminitis, pancreatitis, and hyperammonemia
Time Frame
During patient hospital stay for up to 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Admission to Trauma Services Heavy drinkers based on social history Men <65 years: > 4 drinks per day or 14 per week Women: > 3 drinks per day or 7 drinks per week All adults >65 years: > 3 drinks per day or 7 drinks per week Moderate or severe alcohol use disorder based on social history and DSM-5 criteria Moderate: Presence of 4-5 symptoms based on social history Severe: Presence of 6 symptoms based on social history Exclusion Criteria: Intubated patients Glasgow Coma Score <8 Grade IV liver laceration or greater Child-Pugh Class B or greater, history of cirrhosis, or cirrhosis identified by radiographic imaging upon admission Transaminase (AST/ALT) elevation of ≥ 2x normal Anticipated admission less than 72 hours Levetiracetam administration for seizure prophylaxis secondary to a traumatic brain injury Patient with VPA as home medication Known allergy to VPA Patients with pre-existing blood dyscrasias, i.e. thrombocytopenia (platelet count < 50,000, etc) Inability to obtain social history from patient, surrogate, family member or an individual deemed to be knowledgeable about the patient's social history Pregnancy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Audis Bethea, PharmD, BCPS
Phone
304-388-6260
Email
audis.bethea@camc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Audis Bethea, PharmD, BCPS
Organizational Affiliation
Charleston Area Medical Center Health System
Official's Role
Principal Investigator
Facility Information:
Facility Name
Charleston Area Medical Center, General Hospital, Level 1 Trauma Center
City
Charleston
State/Province
West Virginia
ZIP/Postal Code
25301
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Audis Bethea, PharmD, BCPS
Phone
304-388-3653
Email
audis.bethea@camc.org
First Name & Middle Initial & Last Name & Degree
Audis Bethea, PharmD, BCPS
First Name & Middle Initial & Last Name & Degree
Richard Umstot, MD
First Name & Middle Initial & Last Name & Degree
Chelsea Knotts, MD
First Name & Middle Initial & Last Name & Degree
Brent Stover, MA, LPC, ADC
First Name & Middle Initial & Last Name & Degree
Damayanti Samanta, MS
First Name & Middle Initial & Last Name & Degree
Julton Tomanguillo Chumbe, MD
Facility Name
Charleston Area Medical Center
City
Charleston
State/Province
West Virginia
ZIP/Postal Code
25304
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Audis Bethea, PharmD, BCPS
Phone
304-388-3653
Email
audis.bethea@camc.org
First Name & Middle Initial & Last Name & Degree
Audis Bethea, PharmD, BCPS
First Name & Middle Initial & Last Name & Degree
Richard Umstot, MD
First Name & Middle Initial & Last Name & Degree
Chelsea Knotts, MD
First Name & Middle Initial & Last Name & Degree
Brent Stover, MA, LPC, ADC
First Name & Middle Initial & Last Name & Degree
Damayanti Samanta, MS
First Name & Middle Initial & Last Name & Degree
Julton Tomanguillo Chumbe, MD

12. IPD Sharing Statement

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Assessment of Valproate on Ethanol Withdrawal

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