Valproic Acid for Treatment of Hyperactive or Mixed Delirium in ICU
Information source: Stanford University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hyperactive Delirium; Mixed Delirium
Intervention: Valproic Acid (Drug); Placebo (Drug); Haloperidol (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Stanford University Official(s) and/or principal investigator(s): Yelizaveta Sher, M.D., Principal Investigator, Affiliation: Stanford University Jose R Maldonado, M.D., Study Director, Affiliation: Stanford University
Overall contact: Shengchun Wang, Ph.D, Phone: 5183342513, Email: swang6@stanford.edu
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.
Clinical Details
Official title: Valproic Acid for Treatment of Hyperactive or Mixed Delirium in ICU
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Time to delirium resolution
Secondary outcome: Use of as needed anti-psychotic agentMortality rate Side effects from medications (Side effects from VPA (LFT increase, platelet decrease, bleeding), haloperidol side effects (QTc prolongation, extrapyramidal side effects) Intensity of delirium (measured by ICDCS delirium severity scale) Length of ICU stay Length of hospital stay
Detailed description:
The investigators plan to investigate the efficacy and tolerability of scheduled VPA as
compared to placebo with as needed basis (PRN) haloperidol (as a back-up in both arms) for
treatment of hyperactive or mixed delirium. Patients will be randomized to scheduled VPA or
placebo (normal saline) and both arms will have flexible PRN dosing of haloperidol. Thus,
the investigators plan to learn the time to delirium resolution in patients treated with VPA
versus placebo; percentage of patients responding to VPA versus placebo; tolerability of VPA
versus placebo. If addition of scheduled VPA proves to shorten time to delirium resolution
as compared to placebo, lead to less use of haloperidol, and/or have fewer side effects, it
would provide a very important addition to our limited evidence-based repertoire of delirium
treatment. Moreover, this pilot study would then pave the way for the bigger randomized
control trial powered to detect its effect size.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- patients 18 years of age and older
- admitted to surgical ICU
- diagnosed with hyperactive or mixed delirium
Exclusion Criteria:
- 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.
Locations and Contacts
Shengchun Wang, Ph.D, Phone: 5183342513, Email: swang6@stanford.edu
Stanford Hospital and Clinics, Stanford, California 94305, United States; Recruiting Shengchun Wang, Ph.D, Phone: 518-334-2513, Email: swang6@stanford.edu
Additional Information
Starting date: January 2015
Last updated: February 25, 2015
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