Pilot Study of Haloperidol to Treat Critical Illness Delirium

NCT ID: NCT00429676

Last Updated: 2012-11-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-31
• Study Completion Date: 2007-09-30

Brief Summary

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

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.

Conditions

Delirium; Critical Illness

Keywords

Randomized; Controlled; Trial; Delirium; Haloperidol

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Haloperidol

Intervention Type: DRUG

Eligibility Criteria

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)

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

Sponsors

Denver Health Medical Center

OTHER

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ivor S Douglas, MD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado Department of Pulmonary and Critical Care Medicine

Locations

Denver Health Medical Center

Denver, Colorado, United States

Countries

United States

References

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. doi: 10.1001/jama.286.21.2703.

Reference Type: BACKGROUND

PMID: 11730446 (View on PubMed)

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. doi: 10.1001/jama.291.14.1753.

Reference Type: BACKGROUND

PMID: 15082703 (View on PubMed)

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. doi: 10.1097/01.ccm.0000150743.16005.9a.

Reference Type: BACKGROUND

PMID: 15644675 (View on PubMed)

Other Identifiers

05-0362

Identifier Type: -

Identifier Source: org_study_id