Managing Agitated Delirium With Neuroleptics and Anti-Epileptics as a Neuroleptic Sparing Strategy

Delirium Clinical Trial

Official title:

Managing Agitated Delirium With Neuroleptics and Anti-Epileptics as a Neuroleptic Sparing Strategy

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05431595
• Other study ID #: 2022-0172
• Secondary ID: NCI-2022-05252
• Status: Enrolling by invitation
• Phase: Phase 2/Phase 3
• Start date: July 19, 2022
• Est. completion date: February 2, 2027

Study information

• Verified date: May 2024
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 150
• Est. completion date: February 2, 2027
• Est. primary completion date: February 2, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. [Patients] Diagnosis of advanced cancer (defined as locally advanced, metastatic recurrent, or incurable disease)

2. [Patients] Seen by palliative care inpatient consultation team

3. [Patients] Delirium as per DSM-5 criteria

4. [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

5. [Patients] Age 18 years or older

6. [Patients] Permission from clinician from primary team to enroll

7. [Family Caregivers] Patient's spouse, adult child, sibling, parent, other relative, or significant other (defined by the patient as a partner)

8. [Family Caregivers] Age 18 years or older

Exclusion Criteria:

1. [Patients] On scheduled haloperidol >4 mg/d, chlorpromazine >100 mg/d, or valproate >750 mg/d

2. [Patients] History of myasthenia gravis, acute narrow-angle glaucoma, or hepatic encephalopathy as documented in chart

3. [Patients] Hepatic dysfunction (unresolved AST or ALT >2.5x ULN, bilirubin >1.5x ULN or INR >1.5 within past month)

4. [Patients] History of neuroleptic malignant syndrome as documented in chart

5. [Patients] Active seizure disorder within past month as documented in chart

6. [Patients] History of Parkinson's disease or dementia as documented in chart

7. [Patients] History of prolonged QTc interval (>500 ms) if documented by most recent ECG within the past month

8. [Patients] Hypersensitivity to haloperidol, chlorpromazine, or valproate as documented in chart

9. [Patients] Pancreatitis within past month as documented in chart

10. [Patients] Currently on lamotrigine, phenobarbital, or carbamazepine

11. [Patients] Physical signs of impending death such as respiration with mandibular movement and death rattle

12. [Patients] Pregnancy as documented in chart

13. [Patients] Active COVID-19 infection as documented in chart

Related Conditions & MeSH terms

• Delirium
• Epilepsy

Intervention

Drug:
• Haloperidol
Given by Vein (IV)
• Chlorpromazine
Given by Vein (IV)
• Valproate
Given by Vein (IV)
• Placebo
Given by Vein (IV)

Locations

Country	Name	City	State
United States	MD Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	Cancer Prevention Research Institute of Texas

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	through study completion, an average of 1 year

External Links

•   MD Anderson Cancer Center