The Effect of Guanfacine on Delirium in Critically Ill Patients

NCT04578886 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: Guanfacine for Delirium
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Delirium in patients in the intensive care unit (ICU) is a common problem associated with increased mortality and morbidity, including increased hospital and ICU length of stay, greater hospital cost, increased ventilator days, and long-term cognitive disability. Various pharmacologic agents including dopamine antagonists, acetylcholinesterase inhibitors, melatonin, antipsychotics, alpha-2 agonists, and glutamate antagonists are used for treatment of delirium in the ICU despite the lack of clear evidence of efficacy.Since there is no evidence-based pharmacologic treatment of ICU delirium, current therapy is focused on non-pharmacologic prevention techniques and pharmacologic agents are used once delirium is established. Guanfacine, an alpha-2 agonist, has been identified as a potential medication that may be of benefit in the treatment of delirium. The purpose of this study to investigate the effects of guanfacine versus placebo on delirium in critically ill patients admitted to the ICU and to determine whether guanfacine along with standard of care reduces the duration of delirium, compared to standard of care alone.

Conditions

Delirium

Keywords

Delirium; Critically Ill; Guanfacine

Outcome Measures

Primary Outcomes (1)

• Days Without Delirium

  The primary outcome will be the number of days alive without delirium during the 14-day treatment period after randomization. Delirium assessments are measured by the Confusion Assessment Method- Intensive Care Unit (CAM-ICU). CAM-ICU measures a patient's fluctuations in mental status, inattention, disorganized thinking, and consciousness.The CAM-ICU will be used twice daily with all patients while admitted until ICU discharge. Patients will be diagnosed as delirious when they have at least one positive CAM-ICU on the day of assessment up to ICU discharge or day 14 after enrollment if remaining in ICU. Patients will be diagnosed as delirium free when they have four (4) negative consecutive CAM-ICU assessments.

  From the time of ICU admission up to 14 days

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo, lactulose monohydrate, encapsulated, once nightly at 2100, for up to 14 day study duration or otherwise indicated by study protocol.

Drug: Placebo

Guanfacine

EXPERIMENTAL

Guanfacine immediate-release, 2mg dose, over-encapsulated tablet, once nightly at 2100, for up to 14 day study duration or otherwise indicated by study protocol.

Drug: Guanfacine

Interventions

Guanfacine DRUG

Guanfacine 2 mg administered at 21:00 for up to 14 days or otherwise indicated by study protocol.

Guanfacine

Placebo DRUG

Placebo, administered at 2100 for up to 14 days or otherwise indicated by study protocol.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients admitted to the UAB hospital Surgical Intensive Care Unit (SICU)
• years of age or older
• Expected total ICU length of stay of 72 hours or more per treating physician
• Diagnosed with delirium based on CAM-ICU assessment (see attached CAM-ICU assessment form)

You may not qualify if:

• Patients younger than 18 years old
• Expected discharge from ICU within 72 hours of admission
• Expected or inevitable death with 48 hours of enrollment
• Pregnancy or breast feeding
• Non-English speaking
• Patients unable to be assessed by CAM-ICU due to neurologic illness
• Altered consciousness unable to participate in CAM-ICU assessment
• Patients with previous diagnosis of chronic, acute, subacute neurologic disease, or neurodegenerative disease
• Mental illness and/or psychosis
• Acute alcohol withdrawal
• No enteral route available for administration
• Treating physician refusal of enrollment based on severe hypotension (defined as requiring a vasopressor for longer than 24 hours) or bradycardia (Hr\<50 bpm) at the time of screening
• Hepatic encephalopathy
• Blind or Hearing impaired
• Taking Guanfacine, for any reason

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama at Birmingham Hospital

Birmingham, Alabama, 35295, United States

Location

Related Publications (1)

• Arnsten AFT, Ishizawa Y, Xie Z. Scientific rationale for the use of alpha2A-adrenoceptor agonists in treating neuroinflammatory cognitive disorders. Mol Psychiatry. 2023 Nov;28(11):4540-4552. doi: 10.1038/s41380-023-02057-4. Epub 2023 Apr 7.

  PMID: 37029295 DERIVED

MeSH Terms

Conditions

Delirium; Critical Illness

Interventions

Guanfacine

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Disease Attributes; Pathologic Processes

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids

Limitations and Caveats

This study is limited by the nature of being a single center design with a small sample size. The study population is in the critically ill surgical patient and this acuity and demographic may limit the external validity.

Results Point of Contact

• Title: Dr. Andrew B. Barker, MD
• Organization: University of Alabama at Birmingham, Department of Anesthesiology and Perioperative Medicine

abbarker@uabmc.edu

205-934-6007

Study Officials

• Andrew Barker, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 18, 2020
• First Posted: October 8, 2020
• Study Start: November 23, 2020
• Primary Completion: February 20, 2023
• Study Completion: April 1, 2023
• Last Updated: April 15, 2025
• Results First Posted: April 17, 2024

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)