Efficacy and Safety of Risperidone and Trazodone Monotherapy and Combination Therapy in Critically Ill Patients With Delirium

NCT02118688 | Withdrawn Phase 4 DMC

• 1 other identifier: ICUDelirium
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this randomized clinical trial is to determine whether risperidone alone, trazodone alone, or a combination of risperidone and trazodone is superior for the treatment of ICU acquired delirium. The hypothesis is that combination therapy is superior to either agent alone in treating ICU acquired delirium and sustaining delirium free time.

Conditions

Delirium; Agitation

Outcome Measures

Primary Outcomes (1)

• The number of days patients are without delirium during the study period (delirium-free days)

  The number of days patients are without delirium during the study period (delirium-free days)

  Every 24 hours (up to 14 days)

Secondary Outcomes (12)

• Daily prevalence of delirium as indicated by a positive Confusion Assessment Method in the ICU (CAM-ICU)

  Every 24 hours (up to 14 days)

• Resolution of delirium as indicated by a negative Confusion Assessment Method in the ICU (CAM-ICU) for more than 24 hours

  Every 24 hours (up to 14 days)

• The number of patients who require rescue medications, the type of rescue medications utilized, and the amount of rescue medications per day

  Every 24 hours (up to 14 days)

• The number of patients who receive sedative agents, amount of midazolam equivalents per day, and the number of days in which patients receive a sedative agent

  Every 24 hours (up to 14 days)

• The number of patients who receive pain medications, amount of fentanyl equivalents per day, and the number of days in which patients receive a pain medication

  Every 24 hours (up to 24 hours)

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Drug: Placebo * Placebo suspension administered PO/NG/FT q12h to mimic risperidone * Placebo suspension administered PO/NG/FT q8h to mimic trazodone

Drug: Placebo

Risperidone alone

ACTIVE COMPARATOR

Drug: Risperidone * Initiate risperidone at 1 mg PO/NG/FT q12h * Risperidone dose can be titrated upwards every 24 hours by increments of 0.5 mg per dose * Maximum risperidone daily dose of 6 mg per day (3 mg every 12 hours)

Drug: Risperidone; Drug: Placebo

Trazodone alone

ACTIVE COMPARATOR

Drug: Trazodone * Initiate trazodone dosing at 50 mg PO/NG/FT q8h * Trazodone dose can be titrated upwards every 24 hours by 25 mg per dose * Maximum trazodone daily dose 600 mg per day (200 mg every 8 hours)

Drug: Trazodone; Drug: Placebo

Risperidone and Trazodone combination

ACTIVE COMPARATOR

Drug: Risperidone * Initiate risperidone at 1 mg PO/NG/FT q12h * Risperidone dose can be titrated upwards every 24 hours by increments of 0.5 mg per dose * Maximum risperidone daily dose of 6 mg per day (3 mg every 12 hours) Drug: Trazodone * Initiate risperidone at 1 mg PO/NG/FT q12h * Risperidone dose can be titrated upwards every 24 hours by increments of 0.5 mg per dose * Maximum risperidone daily dose of 6 mg per day (3 mg every 12 hours)

Drug: Risperidone; Drug: Trazodone

Interventions

Risperidone DRUG

Risperidone alone; Risperidone and Trazodone combination

Trazodone DRUG

Risperidone and Trazodone combination; Trazodone alone

Placebo DRUG

Placebo; Risperidone alone; Trazodone alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than 18 years old who are admitted for more than 24 hours in the MICU or SICU
• Patients diagnosed with delirium by primary team (screened positive for delirium using the CAM-ICU or with clinical manifestations of delirium)
• Patients have an order for as-needed haloperidol or have received a one-time dose of haloperidol within 24 hours of randomization
• Patients must be tolerating enteral feeding (greater than 20 mL/hour for more than 12 hours)

You may not qualify if:

• Patients who are unlikely to survive 24 hours after admission to the ICU
• Patients who are admitted with a primary neurological condition or injury (i.e. stroke, active seizures, prolonged coma, overdose)
• Patients who can not actively participate in delirium assessment
• Patients actively withdrawing from alcohol or narcotics
• Patients who were treated with any antipsychotic or trazodone within 30 days prior to ICU admission
• Patients with a marked baseline prolongation of the QTc interval (repeated demonstration of QTc interval greater 500 milliseconds (msec))
• Patients with a history of Torsades de Pointes
• Patients with current treatment with an agent having either the potential to affect or increase the risk of QTc prolongation (e.g. erythromycin, any class Ia, Ic, or III antiarrhythmics)
• Patients being treated with a neuromuscular blocker
• Patients in whom haloperidol, risperidone, or trazodone is contraindicated
• Pregnant patients or patients who are breast-feeding
• Patients with a modified Blessed dementia rating scale score ≥4 or an Informant Questionnaire of Cognitive Dysfunction in the Elderly Score ≥4
• Patients in which informed consent can not be obtained from the legally authorized representative

Sponsors & Collaborators

• Rochester General Hospital: lead

Study Sites (1)

Rochester General Hospital

Rochester, New York, 14621, United States

Location

MeSH Terms

Conditions

Delirium; Psychomotor Agitation

Interventions

Risperidone; Trazodone

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Dyskinesias; Psychomotor Disorders; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Pyridones; Pyridines

Study Officials

• Mindee S Hite, Pharm.D.

  Rochester General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Critical Care Clinical Pharmacy Specialist

Study Record Dates

• First Submitted: April 9, 2014
• First Posted: April 21, 2014
• Study Start: March 1, 2011
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: September 10, 2019

Record last verified: 2019-09

Locations

US (1)