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

NCT ID: NCT02118688

Last Updated: 2019-09-10

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2016-03-31

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.

Detailed Description

Delirium is defined as a disturbance of consciousness characterized by an acute onset of impaired cognitive function. Although delirium is thought to be common in the Intensive Care Unit (ICU) there are few studies that have evaluated its incidences, risks and outcomes. It has been associated with increased morbidity, and mortality and increased cost to the healthcare system. In addition to the uncertainty of the incidence of ICU delirium, there is a lack of information about the effects that certain pharmacological treatments have on delirious patients.

The rationale for this study is to evaluate the efficacy and safety of risperidone alone, trazodone alone, and risperidone plus trazodone for the treatment of delirium in critically ill patients when compared to placebo.

Conditions

Delirium; Agitation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Drug: Placebo

• Placebo suspension administered PO/NG/FT q12h to mimic risperidone
• Placebo suspension administered PO/NG/FT q8h to mimic trazodone

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Risperidone alone

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)

Group Type: ACTIVE_COMPARATOR

Risperidone

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Trazodone alone

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)

Group Type: ACTIVE_COMPARATOR

Trazodone

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Risperidone and Trazodone combination

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)

Group Type: ACTIVE_COMPARATOR

Risperidone

Intervention Type: DRUG

Trazodone

Intervention Type: DRUG

Interventions

Risperidone

Intervention Type: DRUG

Trazodone

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rochester General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Mindee S. Hite

Critical Care Clinical Pharmacy Specialist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mindee S Hite, Pharm.D.

Role: PRINCIPAL_INVESTIGATOR

Rochester General Hospital

Locations

Rochester General Hospital

Rochester, New York, United States

Countries

United States

Other Identifiers

ICUDelirium

Identifier Type: -

Identifier Source: org_study_id