Pilot Study of Haloperidol to Treat Critical Illness Delirium

Critical Illness Clinical Trial

Official title:

A Randomized Prospective Pilot Study Of Haloperidol In Addition To Standard Sedation In Mechanically Ventilated Patients With Delirium

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00429676
• Other study ID #: 05-0362
• Status: Completed
• Phase: Phase 2
• First received: January 30, 2007
• Last updated: November 13, 2012
• Start date: December 2005
• Est. completion date: September 2007

Study information

• Verified date: November 2009
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The goal of this study is to determine whether haloperidol reduces the time on the breathing machine in critically ill patients with delirium.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: September 2007
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Critical Illness
• Delirium

Intervention

Drug:
• Haloperidol

Locations

Country	Name	City	State
United States	Denver Health Medical Center	Denver	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	Denver Health Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (3)

Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, Truman B, Speroff T, Gautam S, Margolin R, Hart RP, Dittus R. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA. 2001 Dec 5;286(21):2703-10. — View Citation

Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr, Inouye SK, Bernard GR, Dittus RS. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004 Apr 14;291(14):1753-62. — View Citation

Milbrandt EB, Kersten A, Kong L, Weissfeld LA, Clermont G, Fink MP, Angus DC. Haloperidol use is associated with lower hospital mortality in mechanically ventilated patients. Crit Care Med. 2005 Jan;33(1):226-9; discussion 263-5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ventilator-free days out of the first 28
Secondary	Duration of delirium
Secondary	Length of hospitalization
Secondary	Cost of hospitalization
Secondary	28-day mortality
Secondary	Usage of other sedatives
Secondary	Serum markers of delirium (neuron-specific enolase and protein S-100B)
Secondary	Cognitive-function scores at the time of ICU discharge, hospital discharge, and six-month follow-up