Clinical trial NCT02343575: Valproic Acid for Treatment of Hyperactive or Mixed Delirium in ICU
Official title: Valproic Acid for Treatment of Hyperactive or Mixed Delirium in ICU
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Hyperactive Delirium
Mixed Delirium
Keywords: Hyperactive delirium
Mixed delirium
Anti-psychotic
Haldol
Valproic Acid
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2015-01-22
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Time to Delirium Resolution
timeFrame: Up to 5 days
Secondary outcomes:
measure: Use of as Needed Anti-psychotic Agent
timeFrame: Up to 5 days
measure: Side Effects From Medications
timeFrame: Up to 5 days
measure: Intensity of Delirium as Measured by the Intensive Care Delirium Screening Checklist (ICDSC) Delirium Severity Scale
timeFrame: Up to 5 days
measure: Length of ICU Stay
timeFrame: During expected average hospitalization (of 1 month)
measure: Length of Hospital Stay
timeFrame: During expected average hospitalization (of 1 month)
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Hospital and Clinics
state: California
Study officials:
affiliation: Stanford University
name: Yelizaveta Sher, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Jose R Maldonado, M.D.
role: STUDY_DIRECTOR
References: