Pilot Study of Haloperidol to Treat Critical Illness Delirium

This study has been completed.
Denver Health Medical Center
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
First received: January 30, 2007
Last updated: November 13, 2012
Last verified: November 2009
The goal of this study is to determine whether haloperidol reduces the time on the breathing machine in critically ill patients with delirium.

Condition Intervention Phase
Critical Illness
Drug: Haloperidol
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Prospective Pilot Study Of Haloperidol In Addition To Standard Sedation In Mechanically Ventilated Patients With Delirium

Resource links provided by NLM:

Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Ventilator-free days out of the first 28

Secondary Outcome Measures:
  • Duration of delirium
  • Length of hospitalization
  • Cost of hospitalization
  • 28-day mortality
  • Usage of other sedatives
  • Serum markers of delirium (neuron-specific enolase and protein S-100B)
  • Cognitive-function scores at the time of ICU discharge, hospital discharge, and six-month follow-up

Estimated Enrollment: 20
Study Start Date: December 2005
Study Completion Date: September 2007
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Detailed Description:

Delirium is a frequent end-organ complication of critical illness and is an independent predictor of mortality in mechanically ventilated patients. However, management of delirium is a major therapeutic challenge and it is unknown if current therapies are disease modifying or function only as symptom management. Haloperidol has been demonstrated to reduce delirium in retrospective studies.

This study is a pilot prospective randomized clinical trial in the Denver Health Medical ICU to determine if haloperidol in addition to an evidence-based standard-of-care sedation protocol for the management of delirium results in a shortened duration of intubation and improvements in post-extubation cognitive status. The haloperidol dose is administered using titration-protocol guided by nursing assessment of delirium using the confusion assessment method for the ICU (CAM-ICU). The primary outcome is ventilator-free days out of the first 28, and secondary outcomes include duration of delirium, length and cost of hospitalization, 28-day mortality, usage of other sedatives, serum markers of delirium (neuron-specific enolase and protein S-100B), and cognitive-function scores at the time of ICU discharge, hospital discharge, and six-month follow-up.

The goal of the 20-patient pilot is demonstrating safety of the haloperidol protocol, as evaluated by an independent data-safety monitoring board. Following approval of the DSMB, 122 more patients will be enrolled in the full RCT to achieve power for an 80% chance of detecting a 40% decrease in duration of intubation with P < 0.05.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Mechanically ventilated within 24 hours of arrival to the ICU
  • Delirium as assessed by CAM-ICU within 24 hours of arrival to the ICU
  • Age > 18

Exclusion Criteria:

  • Known allergy to haloperidol or other neuroleptics
  • Neurological injury or trauma
  • < 24 hours after a major operation
  • History of Axis I psychiatric disorder or significant dementia
  • Baseline QTc of > 500 msec or a pacemaker which makes the QTc uninterpretable
  • History of seizure disorder
  • Morbid obesity (> 1kg/cm body weight)
  • Hepatic failure (Child's Class C)
  • Neuromuscular disease (C5 or higher spinal cord injury, ALS, Guillain-Barre Syndrome, and myasthenia gravis)
  • Malignancy or other irreversible disease or condition for which 6 month mortality is estimated to be ≥ 50%
  • Pregnancy (negative pregnancy test required for women of child-bearing potential)
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00429676

United States, Colorado
Denver Health Medical Center
Denver, Colorado, United States, 80204
Sponsors and Collaborators
University of Colorado, Denver
Denver Health Medical Center
Principal Investigator: Ivor S Douglas, MD University of Colorado Department of Pulmonary and Critical Care Medicine
  More Information

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT00429676     History of Changes
Other Study ID Numbers: 05-0362 
Study First Received: January 30, 2007
Last Updated: November 13, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of Colorado, Denver:

Additional relevant MeSH terms:
Critical Illness
Disease Attributes
Mental Disorders
Nervous System Diseases
Neurobehavioral Manifestations
Neurocognitive Disorders
Neurologic Manifestations
Pathologic Processes
Signs and Symptoms
Haloperidol decanoate
Anti-Dyskinesia Agents
Antipsychotic Agents
Autonomic Agents
Central Nervous System Depressants
Dopamine Agents
Dopamine Antagonists
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Psychotropic Drugs
Tranquilizing Agents

ClinicalTrials.gov processed this record on May 22, 2016