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

Sponsor

M.D. Anderson Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05431595

Collaborator

Cancer Prevention Research Institute of Texas (Other)

150

Enrollment

Location

Arms

Anticipated Duration (Months)

4.8

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Delirium Epileptics Neuroleptics	Drug: Haloperidol Drug: Chlorpromazine Drug: Valproate Drug: Placebo	Phase 2/Phase 3

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

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

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

Anticipated Study Start Date :

Dec 30, 2022

Anticipated Primary Completion Date :

Aug 1, 2025

Anticipated Study Completion Date :

Aug 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 Participants will receive haloperidol by vein every 12 hours (or more often, as needed).	Drug: Haloperidol Given by Vein (IV)
Experimental: Group 2 Participants will receive chlorpromazine by vein every 12 hours (or more often, as needed).	Drug: Chlorpromazine Given by Vein (IV) Other Names: Chlorpromazine hydrochloride, Thorazine®
Experimental: Group 3 Participants will receive valproate by vein every 12 hours.	Drug: Valproate Given by Vein (IV) Other Names: Depakene Valproate Acid
Experimental: Group 4 Participants will receive placebo every by vein every 12 hours.	Drug: Placebo Given by Vein (IV)

Outcome Measures

Primary Outcome Measures

Edmonton Symptom Assessment Scale Questionnaire [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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

[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 in the past 24 h requiring at least 1 dose of rescue medicationa
[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

Exclusion Criteria:

[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)b
[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
[Patients] History of prolonged QTc interval (>500 ms) if documented by most recent ECG within the past monthc
[Patients] Hypersensitivity to haloperidol, chlorpromazine, or valproate as documented in chart
[Patients] Pancreatitis within past month as documented in chart
[Patients] Currently on carbapenems, 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