Valproic Acid for Treatment of Hyperactive or Mixed Delirium in ICU
| Status: | Suspended |
|---|---|
| Conditions: | Neurology, Psychiatric |
| Therapuetic Areas: | Neurology, Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/17/2018 |
| Start Date: | January 2015 |
| End Date: | June 2020 |
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.
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.
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.
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.
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.
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