Valproic Acid for Treatment of Hyperactive or Mixed Delirium in ICU
Phase: PHASE4
Conditions: Hyperactive Delirium, Mixed Delirium
Sponsor: Stanford University

 
 
 
 
 
Valproic Acid for Treatment of Hyperactive or Mixed Delirium in ICU 
Study Protocol 
NCT02343575 
Document Date: March 12, 2014 

VPA as an Adjunct Treatment for Hyperactive/Mixed Delirium Study 
 
1 
 
Medication adjustment protocol: 
Adjustments can take place every 24 hours according to the below schedule: 
If study physician decides based on the below criteria that medications need to change, they notify 
RA/pharmacy 
 
Placebo arm 
VPA arm 
1. start 
 Placebo PO BID 
 Rescue: HAL IV 1-5 mg 
Q4hr PRN 
 
 VPA PO 500 mg BID 
 Rescue: HAL IV 1-5 mg 
Q4hr PRN 
 
2. If ICDCS = or > 4, RASS = 
or > 1 and patient cont 
to meet criteria for 
hyperactive/mixed 
delirium, consider 
increasing meds 
according to protocol 
 Placebo PO BID 
 Rescue: HAL IV 1-5 mg 
Q4hr PRN 
 
 VPA 500 mg PO q am, 1000 
mg PO QHS 
 Rescue: HAL IV 1-5 mg 
Q4hr PRN 
3. If need to increase 
 Placebo PO BID 
 Rescue: HAL IV 1-5 mg 
Q4hr PRN 
 VPA 500 mg PO q am, 1500 
mg PO QHS 
 Rescue: HAL IV 1-5 mg 
Q4hr PRN 
 
4. If need to increase 
 
 Placebo PO BID 
 Rescue: HAL IV 1-5 mg 
Q4hr PRN 
 VPA 500 mg PO Q am, 2000 
mg PO QHS 
 Rescue: HAL IV 1-5 mg 
Q4hr PRN  
 
 
Blinded physician evaluates patient daily: clinical exam, ICDSC, DSM V criteria for delirium, 
EPS, primitive reflexes 
 
Research Assistant daily collects CBC (esp platelets), CMP (esp LFTs), INR, QTc, EPS side effects 
 
If QTC increases by 20% from initiation of medication or equals 500 or above, LFTs increase 
(ALT > 150, AST> 80) or platelets decrease by 30% or are below 150, research assistant 
consults with affiliated physician (#2). Physician #2 carefully examines situation and decides 
whether any of these changes can be due to study medication. 
o  If No  note is taken, study continues as designed, no unblinding necessary.  
o If Yes study physician #1 is informed and unblinded and the best clinical decision for 
the patient is taken 
 
Patients will be in the study for total of 7 days or until resolution of delirium (ICDSC < 4 plus 24 
hours), whichever is shorter time. If patients need continued treatment after the study 
resolution, they will be followed by the regular psychiatry consult team.