Phenobarbital for Agitated Delirium

The goal of this clinical trial is to test whether the medication phenobarbital is as effective for treating agitated delirium among adult patients admitted to the intensive care unit. Agitated delirium is a condition involving confusion and impulsiveness which is dangerous to both patients and healthcare providers.

The main questions this trial aims to answer include:

• Can phenobarbital decrease the amount of time patients with agitated delirium spend in the intensive care unit and the hospital?
• Does phenobarbital decrease the amount of additional calming medications patients with agitated delirium need?

Researchers in this study will compare phenobarbital to other medications commonly used to treat agitated delirium.

Participants will be monitored closely to make sure they remain safe and to measure how well their agitation and confusion are managed while they are in the ICU.

Study Overview

• Status: Not yet recruiting
• Conditions: Delirium Confusional State; Hyperactive Delirium; Delirium in the Intensive Care Unit; Agitated Delirium
• Intervention / Treatment: Drug: Phenobarbital; Drug: Conventional therapy group

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Keith W Van Dusen, M.D.; Phone Number: (919) 684-8111; Email: kwv@duke.edu

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27704
      • Duke Regional Hospital
      • Contact: Keith W Van Dusen, M.D.; Phone Number: (919) 684-8111

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult Patients identified by providers to have agitated or hyperactive delirium

Exclusion Criteria:

• Pregnancy
• Incarceration
• Severe liver disease
• Allergy or prior adverse reaction to phenobarbital or antipsychotic drugs (depending on the month of therapy initiation)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phenobarbital Therapy; In alternating months, patients starting therapy for agitated delirium will be assigned to either a phenobarbital regimen or a conventional antipsychotic-based regimen. Patients assigned to Phenobarbital Therapy will receive this drug according to a validated protocol similar to that in use for patients with alcohol withdrawal. Additional "rescue" medications including dexmedetomidine will be available as needed.	Drug: Phenobarbital; Patients assigned to Phenobarbital Therapy will receive a validated regimen of this medication to manage their symptoms of agitation and impulsiveness.
Active Comparator: Conventional Therapy; In alternating months, patients starting therapy for agitated delirium will be assigned to either a phenobarbital regimen or a conventional antipsychotic-based regimen. Patients assigned to Conventional Therapy will receive antipsychotics as the primary medications for managing their agitation. Additional "rescue" medications including antipsychotics and dexmedetomidine will be available as needed.	Drug: Conventional therapy group; Patients assigned to Conventional Therapy will receive antipsychotics as the primary medication class used to manage their agitation and impulsiveness.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Provider Compliance	The primary outcome of this study will be provider compliance with the study protocol assessed by selection of Conventional or Phenobarbital Therapy according to the designated month.	Six months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital Length of Stay	Hospital length of stay will be compared between patients receiving Phenobarbital and Conventional therapies.	Six months
ICU Length of Stay	ICU length of stay will be compared between patients receiving Phenobarbital and Conventional therapies.	Six months
Need for rescue medications	Need for additional medications above the Phenobarbital or Conventional therapy regimens will be assessed to determine if patients receiving phenobarbital require fewer doses of additional medications.	Six months

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Keith W. Van Dusen, M.D., Duke University

Publications and helpful links

General Publications

• Malone D, Costin BN, MacElroy D, Al-Hegelan M, Thompson J, Bronshteyn Y. Phenobarbital versus benzodiazepines in alcohol withdrawal syndrome. Neuropsychopharmacol Rep. 2023 Dec;43(4):532-541. doi: 10.1002/npr2.12347. Epub 2023 Jun 27.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: April 17, 2026
• First Submitted That Met QC Criteria: April 17, 2026
• First Posted (Actual): April 23, 2026

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neurobehavioral Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Confusion; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Pyrimidinones; Barbiturates; Phenobarbital
• Other Study ID Numbers: Pro00119911

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Only data pertaining to the primary and secondary objectives (e.g., hospital length of stay, doses of specific medications given, RASS assessments) will be shared. All data will be anonymized.
• IPD Sharing Time Frame: Following completion of the study (Estimated late 2027), for 1 year.
• IPD Sharing Access Criteria: Only researchers who request IPD data and are approved by the DUH IRB to access will be permitted to review IPD data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• 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.: No