Valproic Acid for Treatment of Hyperactive or Mixed Delirium in ICU

NCT02343575 | Terminated Phase 4 Results DMC

• 1 other identifier: 28330
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Delirium is the most often encountered psychiatric diagnosis in the general hospital, with incidence up to 85% in the intensive care unit (ICU) setting and with significant consequences on patients' morbidity and mortality. Currently, although not FDA approved, antipsychotics are often considered the first-line pharmacological treatment. However, there can be limitations to their use, including side effects or lack of efficacy. Valproic acid (VPA) is one of the alternatives at times used in such patients which from limited case series data appears to be helpful and tolerated. VPA can provide relief from agitation that poses a threat to the safety and recovery of the patient. Moreover, mechanistically it addresses the neurochemical and cellular abnormalities inherent in delirium (it has NMDA-antagonist, anti-dopaminergic, GABAergic,anti-inflammatory, anti-apoptotic, and histone deacetylase inhibitor properties, among others). The purpose of this study is to evaluate the efficacy and tolerability of the VPA in the first known to us randomized controlled trial.

Conditions

Hyperactive Delirium; Mixed Delirium

Keywords

Hyperactive delirium; Mixed delirium; Anti-psychotic; Haldol; Valproic Acid

Outcome Measures

Primary Outcomes (1)

• Time to Delirium Resolution

  Delirium resolution was defined as three negative Confusion Assessment Method (CAM) assessments, performed by nurses every 12 hours.

  Up to 5 days

Secondary Outcomes (5)

• Use of as Needed Anti-psychotic Agent

  Up to 5 days

• Side Effects From Medications

  Up to 5 days

• Intensity of Delirium as Measured by the Intensive Care Delirium Screening Checklist (ICDSC) Delirium Severity Scale

  Up to 5 days

• Length of ICU Stay

  During expected average hospitalization (of 1 month)

• Length of Hospital Stay

  During expected average hospitalization (of 1 month)

Study Arms (2)

Valproic Acid

EXPERIMENTAL

1. Start: VPA PO/NGT 500 mg BID 2. If need to increase in 24 or more hours: VPA 500 mg PO/NGT q am, 1000 mg PO/NGT QHS 3. If need to increase in 24 or more hours: VPA 500 mg PO/NGT q am, 1500 mg PO/NGT QHS 4. If need to increase in 24 or more hours: VPA 500 mg PO/NGT Q am, 2000 mg PO/NGT QHS Rescue at all stages: HAL IV 2-5 mg Q4hr PRN

Drug: Valproic Acid; Drug: Haloperidol

Placebo

PLACEBO COMPARATOR

Placebo: PO/NGT BID Rescue: HAL IV 2-5 mg Q4hr PRN

Drug: Placebo; Drug: Haloperidol

Interventions

Valproic Acid DRUG

1\. Start: VPA PO/NGT 500 mg BID 2\. If need to increase in 24 or more hours: VPA 500 mg PO/NGT q am, 1000 mg PO/NGT QHS 3\. If need to increase in 24 or more hours: VPA 500 mg PO/NGT q am, 1500 mg PO/NGT QHS 4.If need to increase in 24 or more hours: VPA 500 mg PO/NGT Q am, 2000 mg PO/NGT QHS

Also known as: VPA, Valproate, Depakote

Valproic Acid

Placebo DRUG

Placebo 500 mg matched to VPA BID PO/NGT

Placebo

Haloperidol DRUG

Both arms (intervention VPA and placebo) will receive flexible as needed haloperidol: Rescue: HAL IV 2-5 mg Q4hr PRN

Also known as: Haldol

Placebo; Valproic Acid

Eligibility Criteria

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

You may qualify if:

• patients 18 years of age and older
• admitted to surgical ICU
• diagnosed with hyperactive or mixed delirium

You may not qualify if:

• hypoactive delirium
• primary team does not think patient is appropriate to participate
• no oral access (PO or NGT)
• non-English speaking
• contraindication to study medications
• pregnant women or woman of child-bearing age not on documented contraception
• QTc = or greater than 480
• hepatic dysfunction
• decreased platelets or platelet dysfunction
• bleeding disorder, current major bleeding
• history of NMS, epilepsy, or PD
• diagnosis of schizophrenia, bipolar disorder or schizoaffective disorder
• on warfarin or carbapenems
• delirium due to alcohol withdrawal
• treated with antipsychotics for more than 48 hours prior to study enrollment.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford Hospital and Clinics

Stanford, California, 94305, United States

Location

MeSH Terms

Interventions

Valproic Acid; Haloperidol

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids; Butyrophenones; Ketones

Limitations and Caveats

The study terminated early and did not meet its planned sample size of 30 participants, leading to a small number of subjects analyzed.

Results Point of Contact

• Title: Yelizaveta Sher, MD
• Organization: Stanford University

ysher@stanford.edu

650-736-0459

Study Officials

• Yelizaveta Sher, M.D.

  Stanford University

  PRINCIPAL INVESTIGATOR

• Jose R Maldonado, M.D.

  Stanford University

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: January 8, 2015
• First Posted: January 22, 2015
• Study Start: January 1, 2015
• Primary Completion: January 1, 2018
• Study Completion: January 1, 2018
• Last Updated: June 26, 2019
• Results First Posted: June 26, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)