Preventing ICU Subsyndromal Delirium Conversion to Delirium With Haloperidol

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2012 by Northeastern University.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Information provided by (Responsible Party):
John Devlin, Northeastern University
ClinicalTrials.gov Identifier:
NCT01174290
First received: July 29, 2010
Last updated: April 27, 2012
Last verified: April 2012
  Purpose

About one-third of the patients who develop mild, acute confusion (i.e., subsyndromal delirium) will go on to develop a severe acute confusional state (i.e. delirium). Delirium refers to a temporary change in the way a person thinks about things. Delirium occurs in patients admitted to the hospital particularly those patients that are very sick, who are given a number of medications, and who are not able to sleep normally. It affects their behavior, their understanding of the people and things around them, and their ability to make decisions. While ICU doctors do everything possible to eliminate the factors that may cause delirium, delirium may cause a person to become very agitated which if not controlled is dangerous to their safety as well as the safety of those around them. As well, if delirium develops in patients in the ICU, it may increase the risk for death, keep patients in both the ICU and hospital for longer and send patients to a long term care facility rather than home after they are discharged from the hospital. A recent medical report found that patients in the ICU who develop subsyndromal delirium have a mortality rate, a length of stay in both the ICU and the hospital, and a transfer rate to a long term care facility that is nearly as great as patients with delirium and greater than patients who develop neither subsyndromal delirium or delirium. Recent studies in non-ICU patients suggest that if a patient who is at high risk for developing delirium receives a medication called an antipsychotic (e.g. haloperidol) they may not be as likely to develop delirium or if they do develop delirium it will not last as long. No studies have evaluated the effect of administering an antipsychotic in patients in the ICU who have subsyndromal delirium. Another study completed in the ICUs at Tufts Medical Center found that there may be an association between the development of delirium in patients with subsyndromal delirium and the use of haloperidol. However, this small study had many limitations and thus it is not currently known whether using haloperidol in patients with subsyndromal delirium will actually cause fewer of these patients to develop delirium. Haloperidol makes a person sleepy and helps control behavior like agitation. Haloperidol is the drug that is used most often to help control delirium in the ICU. This prospective, double-blind, randomized controlled study will determine if haloperidol administered through the vein four times daily (1mg IV q6h) to patients who have subsyndromal delirium, and who are on a breathing machine and being cared for by the Medical ICU service at Tufts Medical Center, will help prevent patients from developing delirium. A total of 68 participants will be enrolled. Exclusion criteria are extensive and include conditions that could affect the ability to determine if delirium is present or increase the risk for side effects related to the administration of haloperidol. Patients older than 80 will be excluded from the study. Study medication (i.e. haloperidol) will be administered until one the following occurs: 1) delirium develops (that is confirmed by a staff psychiatrist or his designate, 2) the patient is discharged from the ICU at Tufts Medical Center, 3) the patient has received haloperidol or placebo for 10 days or 4) an adverse event potentially attributable to the study drug is experienced by a patient that is deemed, in the opinion of a pulmonologist member of the investigative team to warrant discontinuation of therapy. Haloperidol may cause unwanted side effects such as low blood pressure, twitching, and an unsafe abnormal heart rhythm. Patients with chronic confusion (e.g., a dementia such as Alzheimer's Disease) should not receive haloperidol and will not be included in this study. Patients will be carefully monitored for side effects that are potentially related to haloperidol. Patients who become confusion-free in the ICU before they leave the ICU (i.e., have no subsyndromal delirium) will be asked to provide consent for all research activities that occured in the ICU. If patients where cognition is regained (ie. no subsyndromal delirium or delirium) are not willing to provide consent then any study data collected from them while they were in the ICU will be destroyed and they will not be approached to participate in the post-ICU component of the study. This study also seeks to understand how the use of haloperidol in the ICU in patients with subsyndromal delirium may have affect memory, emotional status, happiness, ability to function, and quality of sleep in patients after they leave the ICU. Patients (that do not have delirium based on CAM screening at the time the 3-10 day and 6 month assessments are attempted) will be approached to participate in this post-ICU component of the study.


Condition Intervention Phase
Subsyndromal Delirium
Drug: Haloperidol decanoate
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Preventing ICU Subsyndromal Delirium Conversion to Delirium With Low Dose IV Haloperidol: A Double-Blind, Placebo-Controlled Pilot Study

Resource links provided by NLM:


Further study details as provided by Northeastern University:

Primary Outcome Measures:
  • Conversion from subsyndromal delirium to delirium during the period of study drug administration (up to 10 days). [ Time Frame: ICDSC conducted by bedside nurse every 12 hours during period of study drug administration. All ICDSC >/=4 evaluations (ie. delirium) confirmed by a psychiatrist using DSM-IV criteria. ] [ Designated as safety issue: No ]
    To determine the effect of haloperidol administration in critically ill patients with subsyndromal delirium (ICDSC 1-3) on conversion to delirium (ICDSC >/=4) that is confirmed by a pyschiatrist using DSM-IV criteria) during the period that study drug is administered (up to 10 days).


Secondary Outcome Measures:
  • The number of hours spent agitated (SAS >/=5) as percent of time study drug administered (up to 10 days). [ Time Frame: SAS score evaluated at least every 6 hours by bedside nurse during period of study drug administration (up to 10 days) ] [ Designated as safety issue: No ]
    To determine the effect of haloperidol administration in critically ill patients with subsyndromal delirium on the number of hours spent agitated (SAS>/=5) as a percentage of the total time period study drug is administered (up to 10 days).

  • Duration of mechanical ventilation. [ Time Frame: Time (hours) from initial intubation to extubation (as long as patient not reintubated within 48 hours) ] [ Designated as safety issue: No ]
    To determine the effect of haloperidol administration in critically ill patients with subsyndromal delirium on duration of mechanical ventilation (hours).

  • Clinically significant QTc interval prolongation (≥ 500 msec or an increase of more than 60msec above baseline) [ Time Frame: QTc interval evaluated q12h during period of study drug administration (up to 10 days) ] [ Designated as safety issue: Yes ]
    To determine the number of 12 hour periods during study drug administration (up to 10 days) where clinically significant QTc prolongation occurs (≥ 500 msec or increase more than 60msec above baseline)in critically ill patients with subsyndromal delirium receiving low-dose intravenous haloperidol

  • 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 10 days). Investigator will confirm RN suspicion of extrapyramidal effects using Simpson-Angus Score. ] [ Designated as safety issue: Yes ]
    To determine the number of 12 hour periods where extrapyramidal effects were noted(as evidenced by a positive Simpson-Angus Scale Score) in critically ill patients with subsyndromal delirium receiving low-dose intravenous haloperidol.

  • The number of hours spent excessively sedated (SAS ≤ 2) as a percent of time study drug administered (up to 10 days). [ Time Frame: SAS score evaluated at least every 6 hours by bedside nurse during period of study drug administration (up to 10 days) ] [ Designated as safety issue: Yes ]
    To determine the effect of haloperidol administration in critically ill patients with subsyndromal delirium on the number of hours spent agitated(SAS ≤ 2) as a percentage of the total time period study drug is administered (up to 10 days).

  • Cognition, incidence of anxiety, incidence of depressive symptoms, quality of life (ie., functional status and emotional well being)and sleep quality. [ Time Frame: 6 months after ICU discharge in patients without delirium (CAM-) ] [ Designated as safety issue: No ]
    To determine the effect of haloperidol administration in critically ill patients with subsyndromal delirium on cognition (IQCODE,Frontal Assessment Battery,Cognitive Abilities Screening Instrument), incidence of anxiety and depressive symptoms (Hospital Anxiety and Depression Scale), quality of life (Medical Outcomes Study Short Form Health Survey (SF-36)) and sleep quality (MOS-Sleep Scale) 6 months after ICU discharge.


Estimated Enrollment: 68
Study Start Date: September 2010
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Haloperidol 1mg IV q6h Drug: Haloperidol decanoate

IV q6h.

Study drug will be continued until one of the following study withdrawal/termination criteria is met:

  1. Delirium (ICDSC ≥ 4) develops. The diagnosis of delirium will be confirmed in all instances by the Psychiatric Consultation Service, Division of Psychiatry, Tufts Medical Center using DSM-IV criteria.
  2. The patient is discharged from the ICU at Tufts MC.
  3. 10 days of study drug administration occurs.
  4. The subject experiences an adverse event potentially attributable to the study drug that is deemed, in the opinion of one of the physicians on the study team or the MICU team, to warrant discontinuation of therapy.
Other Name: Haldol
Placebo Comparator: D5W 0.2mL IV q6h Drug: Placebo

D5W 0.2mL IV q6h

Study drug will be continued until one of the following study withdrawal/termination criteria is met:

  1. Delirium (ICDSC ≥ 4) develops. The diagnosis of delirium will be confirmed in all instances by the Psychiatric Consultation Service, Division of Psychiatry, Tufts Medical Center using DSM-IV criteria.
  2. The patient is discharged from the ICU at Tufts MC.
  3. 10 days of study drug administration occurs.
  4. The subject experiences an adverse event potentially attributable to the study drug that is deemed, in the opinion of one of the physicians on the study team or the MICU team, to warrant discontinuation of therapy.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 84 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18-84 years old
  • Subsyndromal delirium (ICDSC of 1-3)
  • Mechanically ventilated
  • No objection from the MICU, CCU, or SICU service attending MD for enrollment
  • Admitted to the MICU, CCU, or SICU service at Tufts Medical Center
  • Patients is expected by their ICU attending physician to require admission to the ICU for ≥ 24 hours

Exclusion Criteria:

  • Pregnancy
  • Delirium (ICDSC ≥ 4)
  • History of severe dementia or an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE)) score ≥ 4
  • IQCODE is not able to be completed.
  • Current treatment with donepezil (aricept), tacrine (cognex), rivastigmine (exelon), or memantine (namenda)
  • Admitted with a neurologic diagnosis (e.g., CVA)
  • Past diagnosis of schizophrenia or a formal thought disorder as defined by DSM IV criteria.
  • Treatment with an antipsychotic agent in the 30 days prior to ICU admission
  • Current treatment with a neuromuscular blocker or dexmedetomidine
  • A patient requiring a level of sedation equivalent to a sedation-agitation scale (SAS) score ≤ 2
  • Inability to conduct valid ICDSC assessment (e.g., coma, deaf)
  • Acute alcohol or drug withdrawal
  • Acute drug overdose
  • Severe encephalopathy
  • History of end stage liver failure (based on presence of ≥ 1 or more of the following: AST/ALT ≥ 2 times ULN, INR ≥ 2, total bilirubin ≥ 1.5
  • Patients with a baseline QTc interval >/= 500 msec or an elevation >/= 60mmHg above baseline
  • Current drug therapy with a class Ia, Ic or III antiarrhythmic other than amiodarone.
  • History of haloperidol allergy
  • History of neuroleptic malignant syndrome.
  • Patients expected to die within 24 hours
  • Inability to obtain informed consent
  • Current participation in another research study.
  • Lack of permission of the patient's primary MICU service attending physician for participation in the study.
  • Current employment at Tufts Medical Center.
  • Age ≥ 85 years.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01174290

Contacts
Contact: John Devlin, PharmD 617-636-6124 j.devlin@neu.edu
Contact: Greg Schumaker, MD 617-636-7426 gschumaker@tuftsmedicalcenter.org

Locations
United States, Massachusetts
Tufts Medical Center Recruiting
Boston, Massachusetts, United States, 02111
Contact: John W Devlin, PharmD    617-636-6124    j.devlin@neu.edu   
Sub-Investigator: John W Devlin, PharmD         
Principal Investigator: Greg Schumaker, MD         
Sub-Investigator: Russel Roberts, PharmD         
Sub-Investigator: Scott Freeman, MD         
Sub-Investigator: Erik Garpestad, MD         
Sub-Investigator: Iona Preston, MD         
Sub-Investigator: Kari Roberts, MD         
Northeastern University Recruiting
Boston, Massachusetts, United States, 02115
Contact: JOhn W Devlin, PharmD    617-636-6124    j.devlin@neu.edu   
Principal Investigator: John W Devlin, PharmD         
Sponsors and Collaborators
Northeastern University
Investigators
Principal Investigator: John W Devlin, PharmD Northeastern University
Principal Investigator: Greg Schumaker, MD Tufts Medical Center
  More Information

Publications:
Responsible Party: John Devlin, Principal Investigator, Northeastern University
ClinicalTrials.gov Identifier: NCT01174290     History of Changes
Other Study ID Numbers: 1R15AG034915 - 01A1, R15 AG034915
Study First Received: July 29, 2010
Last Updated: April 27, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Northeastern University:
subsyndromal delirium
delirium
haloperidol
antipsychotic
randomized controlled trial
placebo-controlled
intensive care unit
critical care
subsyndromal delirium in the intensive care unit

Additional relevant MeSH terms:
Delirium
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Haloperidol
Haloperidol decanoate
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Gastrointestinal Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Dyskinesia Agents

ClinicalTrials.gov processed this record on October 01, 2014