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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02118688
Recruitment Status : Withdrawn (Lack of enrollment)
First Posted : April 21, 2014
Last Update Posted : September 10, 2019
Sponsor:
Information provided by (Responsible Party):
Mindee S. Hite, Rochester General Hospital

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.

Condition or disease Intervention/treatment Phase
Delirium Agitation Drug: Risperidone Drug: Trazodone Drug: Placebo Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Risperidone and Trazodone Monotherapy and Combination Therapy in Critically Ill Patients With Delirium: A Four-arm Prospective, Randomized, Double-blind, Placebo-controlled Pilot Study
Study Start Date : March 2011
Actual Primary Completion Date : March 2016
Actual Study Completion Date : March 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Delirium

Arm Intervention/treatment
Placebo Comparator: Placebo

Drug: Placebo

  • Placebo suspension administered PO/NG/FT q12h to mimic risperidone
  • Placebo suspension administered PO/NG/FT q8h to mimic trazodone
Drug: Placebo
Active Comparator: 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)
Drug: Risperidone
Drug: Placebo
Active Comparator: 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)
Drug: Trazodone
Drug: Placebo
Active Comparator: 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)
Drug: Risperidone
Drug: Trazodone



Primary Outcome Measures :
  1. The number of days patients are without delirium during the study period (delirium-free days) [ Time Frame: Every 24 hours (up to 14 days) ]
    The number of days patients are without delirium during the study period (delirium-free days)


Secondary Outcome Measures :
  1. Daily prevalence of delirium as indicated by a positive Confusion Assessment Method in the ICU (CAM-ICU) [ Time Frame: Every 24 hours (up to 14 days) ]
  2. Resolution of delirium as indicated by a negative Confusion Assessment Method in the ICU (CAM-ICU) for more than 24 hours [ Time Frame: Every 24 hours (up to 14 days) ]
  3. The number of patients who require rescue medications, the type of rescue medications utilized, and the amount of rescue medications per day [ Time Frame: Every 24 hours (up to 14 days) ]
  4. 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 [ Time Frame: Every 24 hours (up to 14 days) ]
  5. 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 [ Time Frame: Every 24 hours (up to 24 hours) ]
  6. The number of hours spent agitated (RASS score between +4 and +2) as a percent of the time that the study drug was administered [ Time Frame: Every 24 hours (up to 14 days) ]
  7. The number of hours spent excessively sedated or in a coma state (RASS score between -4 to -5) as a percent of the time that the study drug was administered [ Time Frame: Every 24 hours (up to 14 days) ]
  8. The duration of mechanical ventilation from initial intubation to extubation as long as the patient remained extubated for more than 48 hours. [ Time Frame: Time (hours) from initial intubation to extubation (as long as patient not reintubated within 48 hours) ]
  9. The number of days that the patients were alive and breathing without assistance during the study period (ventilator-free days) [ Time Frame: Time (days) from extubation to patient discharge (as long as patient not reintubated within 48 hours) ]
  10. The number of episodes and number of patients who experience clinically significant QTc prolongation (≥ 500 msec or an increase of more than 60 msec from baseline) [ Time Frame: QTc interval evaluated q12h during period of study drug administration (up to 14 days) ]
  11. The number of episodes and number of patients who experience clinically significant extrapyramidal effects (as evidenced by a positive Simpson-Angus Scale Score) [ Time Frame: Extrapyramidal effects evaluated by bedside nurse q12h during period of study drug administration (up to 14 days). Investigator will confirm RN suspicion of extrapyramidal effects using Simpson-Angus Score. ]
  12. All-cause mortality and 28-day mortality [ Time Frame: At 14 and 28 days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02118688


Locations
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United States, New York
Rochester General Hospital
Rochester, New York, United States, 14621
Sponsors and Collaborators
Rochester General Hospital
Investigators
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Principal Investigator: Mindee S Hite, Pharm.D. Rochester General Hospital
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Responsible Party: Mindee S. Hite, Critical Care Clinical Pharmacy Specialist, Rochester General Hospital
ClinicalTrials.gov Identifier: NCT02118688    
Other Study ID Numbers: ICUDelirium
First Posted: April 21, 2014    Key Record Dates
Last Update Posted: September 10, 2019
Last Verified: September 2019
Additional relevant MeSH terms:
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Delirium
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Risperidone
Trazodone
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents
Anti-Anxiety Agents
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Antidepressive Agents, Second-Generation
Antidepressive Agents