Hyperactive DeliriumPhase 4NCT02343575
Valproic Acid for Treatment of Hyperactive or Mixed Delirium in ICU
A Phase 4 study testing Valproic Acid and Haloperidol in people with Hyperactive Delirium and Mixed Delirium, run by Stanford University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hyperactive Delirium, Mixed Delirium
- What is being tested?
- Valproic Acid and Haloperidol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2015to Jan 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- patients 18 years of age and older
- admitted to surgical ICU
- diagnosed with hyperactive or mixed delirium
Who cannot join
- 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
Show all 15Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford Hospital and Clinics
Stanford, California, 94305
About this study
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.
Read the 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
- Being tested
- Valproic Acid, Placebo, Haloperidol
- Keywords
- Hyperactive delirium, Mixed delirium, Anti-psychotic, Haldol, Valproic Acid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Valproic AcidDrug
Also called VPA, Valproate, Depakote
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
PlaceboDrug
Placebo 500 mg matched to VPA BID PO/NGT
HaloperidolDrug
Also called Haldol
Both arms (intervention VPA and placebo) will receive flexible as needed haloperidol: Rescue: HAL IV 2-5 mg Q4hr PRN
| Study group | Role | What they receive |
|---|---|---|
| Valproic Acid | Experimental | 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 Receives: Drug: Valproic Acid; Drug: Haloperidol |
| Placebo | Placebo comparator | Placebo: PO/NGT BID
Rescue: HAL IV 2-5 mg Q4hr PRN Receives: Drug: Placebo; Drug: Haloperidol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Delirium Resolution
Delirium resolution was defined as three negative Confusion Assessment Method (CAM) assessments, performed by nurses every 12 hours.
Measured: Up to 5 days
Secondary outcomes (5)
Use of as Needed Anti-psychotic Agent
Amount of Haldol administered.
Measured: Up to 5 days
Side Effects From Medications
Side effects may have included liver function test (LFT) increase, platelet decrease, bleeding, or QTc prolongation.
Measured: Up to 5 days
Intensity of Delirium as Measured by the Intensive Care Delirium Screening Checklist (ICDSC) Delirium Severity Scale
The items include the assessment of: (1) consciousness ( deep sedation/coma, agitation, normal wakefulness, or light sedation); (2) inattention; (3) disorientation; (4) hallucination, delusion, or psychosis; (5) psychomotor agitation or retardation; (6) inappropriate speech or mood; (7) sleep-wake cycle disturbances; and (8) fluctuation of symptomatology. The maximum score is eight; scores of ≥4 indicate the presence of delirium and score zero is indicate not in delirium. Each item is scored 0-8.
Measured: Up to 5 days
Length of ICU Stay
Measured: During expected average hospitalization (of 1 month)
Length of Hospital Stay
Participation in the study ended once delirium was resolved and the patient was off study drug. This outcome presents the total length of hospital stay, which may have been longer than participation in the study.
Measured: During expected average hospitalization (of 1 month)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2015 (estimated)
- Study startJan 2015
- Primary completionJan 2018
- Study completionJan 2018
Why it stopped: We did not recruit the research assistant and terminated the study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hyperactive DeliriumStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yelizaveta Sher, Stanford University
- Investigators
- Yelizaveta Sher, M.D., Principal investigator, Stanford UniversityJose R Maldonado, M.D., Study director, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02343575
- Sponsor's protocol ID
- 28330
- Status last verified
- May 2019
- First submitted
- 8 Jan 2015
- Last updated
- 26 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Valproic Acid for Treatment of Hyperactive or Mixed Delirium in ICU
- ClinicalTrials.gov ID
- NCT02343575
- Acronym / sponsor ID
- 28330
- Conditions
- Hyperactive Delirium, Mixed Delirium
- Keywords
- Hyperactive delirium, Mixed delirium, Anti-psychotic, Haldol, Valproic Acid
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: We did not recruit the research assistant and terminated the study
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- Jan 2015
- Primary completion
- Jan 2018 (actual)
- Study completion
- Jan 2018 (actual)
- First posted
- 22 Jan 2015 (estimated)
- Results
- Posted 26 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Valproic Acid | Experimental | Drug: Valproic Acid, Drug: Haloperidol1. 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 |
| Placebo | Placebo comparator | Drug: Placebo, Drug: HaloperidolPlacebo: PO/NGT BID Rescue: HAL IV 2-5 mg Q4hr PRN |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- patients 18 years of age and older
- admitted to surgical ICU
- diagnosed with hyperactive or mixed delirium
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Valproic AcidAlso: VPA, Valproate, Depakote1. 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 | Drug | Valproic Acid |
| PlaceboPlacebo 500 mg matched to VPA BID PO/NGT | Drug | Placebo |
| HaloperidolAlso: HaldolBoth arms (intervention VPA and placebo) will receive flexible as needed haloperidol: Rescue: HAL IV 2-5 mg Q4hr PRN | Drug | Placebo, Valproic Acid |
Primary outcome
Time to Delirium Resolution
Time frame: Up to 5 days
Delirium resolution was defined as three negative Confusion Assessment Method (CAM) assessments, performed by nurses every 12 hours.
5 secondary outcomes
Use of as Needed Anti-psychotic Agent
Time frame: Up to 5 days
Side Effects From Medications
Time frame: Up to 5 days
Intensity of Delirium as Measured by the Intensive Care Delirium Screening Checklist (ICDSC) Delirium Severity Scale
Time frame: Up to 5 days
Length of ICU Stay
Time frame: During expected average hospitalization (of 1 month)
Length of Hospital Stay
Time frame: During expected average hospitalization (of 1 month)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yelizaveta Sher, M.D. principal investigator
Stanford University
Jose R Maldonado, M.D. study director
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Valproic Acid and Haloperidol in people with Hyperactive Delirium and Mixed Delirium, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Delirium Resolution (time frame: Up to 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2019; AzTrials last refreshed its copy on 7 Nov 2026.