DeliriumPhase 2/3NCT05431595
Managing Agitated Delirium With Neuroleptics and Anti-Epileptics as a Neuroleptic Sparing Strategy
A Phase 2/3 study testing Haloperidol, Chlorpromazine and Valproate in people with Delirium and Epileptics, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
To examine the effects of haloperidol, chlorpromazine, valproic acid and placebo, in conjunction with standardized non-pharmacologic interventions, in the first line treatment of agitated delirium in hospitalized patients with cancer. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Delirium, Epileptics, Neuroleptics
- What is being tested?
- Haloperidol, Chlorpromazine and Valproate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Jul 2022to 2 Feb 2027
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- [Patients] Diagnosis of advanced cancer (defined as locally advanced, metastatic recurrent, or incurable disease)
- [Patients] Seen by palliative care inpatient consultation team
- [Patients] Delirium as per DSM-5 criteria
- [Patients] Hyperactive or mixed delirium with either a rescue medication order or any non-pharmacologic measures (e.g. sitter, restraints) for agitation, restlessness, or delirium
- [Patients] Age 18 years or older
- [Patients] Permission from clinician from primary team to enroll
- [Family Caregivers] Patient's spouse, adult child, sibling, parent, other relative, or significant other (defined by the patient as a partner)
- [Family Caregivers] Age 18 years or older
Who cannot join
- [Patients] On scheduled haloperidol >4 mg/d, chlorpromazine >100 mg/d, or valproate >750 mg/d
- [Patients] History of myasthenia gravis, acute narrow-angle glaucoma, or hepatic encephalopathy as documented in chart
- [Patients] Hepatic dysfunction (unresolved AST or ALT >2.5x ULN, bilirubin >1.5x ULN or INR >1.5 within past month)
- [Patients] History of neuroleptic malignant syndrome as documented in chart
- [Patients] Active seizure disorder within past month as documented in chart
- [Patients] History of Parkinson's disease or dementia as documented in chart
Show all 13Show fewer
- [Patients] History of prolonged QTc interval (>500 ms) if documented by most recent ECG within the past month
- [Patients] Hypersensitivity to haloperidol, chlorpromazine, or valproate as documented in chart
- [Patients] Pancreatitis within past month as documented in chart
- [Patients] Currently on lamotrigine, phenobarbital, or carbamazepine
- [Patients] Physical signs of impending death such as respiration with mandibular movement and death rattle
- [Patients] Pregnancy as documented in chart
- [Patients] Active COVID-19 infection as documented in chart
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
David Hui, MD, 713-792-6258, dhui@mdanderson.org
David Hui, MD
About this study
To examine the effects of haloperidol, chlorpromazine, valproic acid and placebo, in conjunction with standardized non-pharmacologic interventions, in the first line treatment of agitated delirium in hospitalized patients with cancer. This double-blind, randomized clinical trial aims to provide evidence on various therapeutic options for palliating delirium, thereby reducing delirium-related distress and ultimately alleviating suffering.
Read the detailed description
Objectives:
Primary objective:
Compare the effect of scheduled haloperidol, chlorpromazine, valproate and placebo (non-pharmacological interventions alone) on the frequency of breakthrough restlessness over 72 hours in patients with agitated delirium seen by the palliative care consultation team. Our working hypothesis is that haloperidol, chlorpromazine, and valproate will lead to fewer episodes of breakthrough restlessness than placebo.
Secondary Objective #1:
Compare the effects of scheduled haloperidol, chlorpromazine, valproate and placebo on (1) RASS-PAL, (2) need for dose escalation, (3) perceived comfort by caregivers and bedside nurses, (4) delirium severity (Memorial Delirium Assessment Scale), (5) delirium-related distress in caregivers and nurses (Delirium Experience Questionnaire), (6) delirium recall in patients (Delirium Recall Questionnaire), (7) symptom expression (Edmonton Symptom Assessment Scale), (8) adverse effects, and (9) survival. Our working hypothesis is that haloperidol, chlorpromazine, and valproate are superior to placebo (non-pharmacologic interventions alone) in improving delirium-related outcomes.
Secondary Objective #2:
Estimate the efficacy of non-pharmacologic interventions alone on breakthrough restlessness. Our working hypothesis is that patients in the placebo group will require fewer breakthrough doses in the 72 hours after implementation of non-pharmacological interventions
- Conditions
- Delirium, Epileptics, Neuroleptics
- Being tested
- Haloperidol, Chlorpromazine, Valproate, Placebo
- Medical subject headings
- Delirium, Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HaloperidolDrug
Given by Vein (IV)
ChlorpromazineDrug
Also called Chlorpromazine hydrochloride, Thorazine®
Given by Vein (IV)
ValproateDrug
Also called Depakene, Valproate Acid
Given by Vein (IV)
PlaceboDrug
Given by Vein (IV)
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Participants will receive haloperidol by vein every 12 hours (or more often, as needed). Receives: Drug: Haloperidol |
| Group 2 | Experimental | Participants will receive chlorpromazine by vein every 12 hours (or more often, as needed). Receives: Drug: Chlorpromazine |
| Group 3 | Experimental | Participants will receive valproate by vein every 12 hours. Receives: Drug: Valproate |
| Group 4 | Experimental | Participants will receive placebo every by vein every 12 hours. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Edmonton Symptom Assessment Scale Questionnaire
Edmonton Symptom Assessment Scale (ESAS)-score scale ranges from (0-10) No pain-0/Worse Possible Pain 10 (0-10)
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2022
- Study start19 Jul 2022
- Primary completion2 Feb 2027 (estimated)
- Study completion2 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DeliriumStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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 2/3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Cancer Prevention Research Institute of Texas
- Responsible party
- Sponsor
- Investigators
- David Hui, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05431595
- Sponsor's protocol ID
- 2022-0172
- Other IDs
- NCI-2022-05252
- Status last verified
- Nov 2025
- First submitted
- 20 Jun 2022
- Last updated
- 18 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Managing Agitated Delirium With Neuroleptics and Anti-Epileptics as a Neuroleptic Sparing Strategy
- ClinicalTrials.gov ID
- NCT05431595
- Acronym / sponsor ID
- 2022-0172
- Conditions
- Delirium, Epileptics, Neuroleptics
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Cancer Prevention Research Institute of Texas
- Study start
- 19 Jul 2022 (actual)
- Primary completion
- 2 Feb 2027 (estimated)
- Study completion
- 2 Feb 2027 (estimated)
- First posted
- 24 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To examine the effects of haloperidol, chlorpromazine, valproic acid and placebo, in conjunction with standardized non-pharmacologic interventions, in the first line treatment of agitated delirium in hospitalized patients with cancer. This double-blind, randomized clinical trial aims to provide evidence on various therapeutic options for palliating delirium, thereby reducing delirium-related distress and ultimately alleviating suffering.
Detailed description
Objectives:
Primary objective:
Compare the effect of scheduled haloperidol, chlorpromazine, valproate and placebo (non-pharmacological interventions alone) on the frequency of breakthrough restlessness over 72 hours in patients with agitated delirium seen by the palliative care consultation team. Our working hypothesis is that haloperidol, chlorpromazine, and valproate will lead to fewer episodes of breakthrough restlessness than placebo.
Secondary Objective #1:
Compare the effects of scheduled haloperidol, chlorpromazine, valproate and placebo on (1) RASS-PAL, (2) need for dose escalation, (3) perceived comfort by caregivers and bedside nurses, (4) delirium severity (Memorial Delirium Assessment Scale), (5) delirium-related distress in caregivers and nurses (Delirium Experience Questionnaire), (6) delirium recall in patients (Delirium Recall Questionnaire), (7) symptom expression (Edmonton Symptom Assessment Scale), (8) adverse effects, and (9) survival. Our working hypothesis is that haloperidol, chlorpromazine, and valproate are superior to placebo (non-pharmacologic interventions alone) in improving delirium-related outcomes.
Secondary Objective #2:
Estimate the efficacy of non-pharmacologic interventions alone on breakthrough restlessness. Our working hypothesis is that patients in the placebo group will require fewer breakthrough doses in the 72 hours after implementation of non-pharmacological interventions
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: HaloperidolParticipants will receive haloperidol by vein every 12 hours (or more often, as needed). |
| Group 2 | Experimental | Drug: ChlorpromazineParticipants will receive chlorpromazine by vein every 12 hours (or more often, as needed). |
| Group 3 | Experimental | Drug: ValproateParticipants will receive valproate by vein every 12 hours. |
| Group 4 | Experimental | Drug: PlaceboParticipants will receive placebo every by vein every 12 hours. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- [Patients] Diagnosis of advanced cancer (defined as locally advanced, metastatic recurrent, or incurable disease)
- [Patients] Seen by palliative care inpatient consultation team
- [Patients] Delirium as per DSM-5 criteria
- [Patients] Hyperactive or mixed delirium with either a rescue medication order or any non-pharmacologic measures (e.g. sitter, restraints) for agitation, restlessness, or delirium
- [Patients] Age 18 years or older
Key exclusion criteria (13 listed)
- [Patients] On scheduled haloperidol >4 mg/d, chlorpromazine >100 mg/d, or valproate >750 mg/d
- [Patients] History of myasthenia gravis, acute narrow-angle glaucoma, or hepatic encephalopathy as documented in chart
- [Patients] Hepatic dysfunction (unresolved AST or ALT >2.5x ULN, bilirubin >1.5x ULN or INR >1.5 within past month)
- [Patients] History of neuroleptic malignant syndrome as documented in chart
- [Patients] Active seizure disorder within past month as documented in chart
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 |
|---|---|---|
| HaloperidolGiven by Vein (IV) | Drug | Group 1 |
| ChlorpromazineAlso: Chlorpromazine hydrochloride, Thorazine®Given by Vein (IV) | Drug | Group 2 |
| ValproateAlso: Depakene, Valproate AcidGiven by Vein (IV) | Drug | Group 3 |
| PlaceboGiven by Vein (IV) | Drug | Group 4 |
Primary outcome
Edmonton Symptom Assessment Scale Questionnaire
Time frame: through study completion, an average of 1 year
Edmonton Symptom Assessment Scale (ESAS)-score scale ranges from (0-10) No pain-0/Worse Possible Pain 10 (0-10)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2025.
- MD Anderson Cancer CenterLink provided by the sponsor.
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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.
David Hui, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Haloperidol, Chlorpromazine and Valproate in people with Delirium and Epileptics, run by M.D. Anderson Cancer Center 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 8 inclusion and 13 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: looking for participants now, as of the sponsor's last update on 18 Nov 2025. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact David Hui, MD ((713) 792-6258, dhui@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Edmonton Symptom Assessment Scale Questionnaire (time frame: through study completion, an average of 1 year). 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 18 Nov 2025.