Valproic Acid for Treatment of Hyperactive or Mixed Delirium in ICU

NCT ID: NCT02343575

Last Updated: 2019-06-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2018-01-31

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.

Conditions

Hyperactive Delirium; Mixed Delirium

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Valproic Acid

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

Group Type: EXPERIMENTAL

Valproic Acid

Intervention Type: 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

Haloperidol

Intervention Type: DRUG

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

Placebo

Placebo: PO/NGT BID

Rescue: HAL IV 2-5 mg Q4hr PRN

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo 500 mg matched to VPA BID PO/NGT

Haloperidol

Intervention Type: DRUG

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

Interventions

Valproic Acid

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

Intervention Type: DRUG

Placebo

Placebo 500 mg matched to VPA BID PO/NGT

Intervention Type: DRUG

Haloperidol

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

Intervention Type: DRUG

Other Intervention Names

VPA; Valproate; Depakote; Haldol

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Yelizaveta Sher

Clinical Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yelizaveta Sher, M.D.

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Jose R Maldonado, M.D.

Role: STUDY_DIRECTOR

Stanford University

Locations

Stanford Hospital and Clinics

Stanford, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

28330

Identifier Type: -

Identifier Source: org_study_id