Preventing Post-Operative Delirium in Patients Undergoing a Pneumonectomy, Esophagectomy or Thoracotomy (PE-POD)

• ClinicalTrials.gov Identifier: NCT02213900
• Recruitment Status: Completed
• First Posted: August 12, 2014
• Results First Posted: April 13, 2017
• Last Update Posted: April 13, 2017
• Sponsor: Indiana University
• Information provided by (Responsible Party): Babar Khan, MD, MS, Regenstrief Institute, Inc.

Study Description

Brief Summary:

The purpose of this study is to investigate the effectiveness of a preventative low-dose of Haloperidol to prevent delirium in patients undergoing a esophagectomy, pneumonectomy or thoracotomy.

Delirium is state of severe confusion and some symptoms include:

• Cannot think clearly
• Have trouble paying attention
• Have a hard time understanding what is going on around them
• May see or hear things that are not there. These things seem very real to them.

Condition or disease	Intervention/treatment	Phase
Delirium; Cognitive Impairment; Post-traumatic Stress Disorder; Depression; Anxiety	Drug: Haloperidol; Drug: Placebo	Phase 4

Detailed Description:

50% of patients who undergo esophageal and/or lung resection suffer from acute brain dysfunction or delirium postoperatively. Delirium is a state of brain failure characterized by disturbance of consciousness with reduced ability to focus, sustain, or shift attention that occurs over a short period of time and tends to fluctuate over the course of the day. Presence of delirium in the post-operative phase is associated with a longer length of both intensive care unit and hospital stay, increased health-care costs, long-term functional and cognitive decline, and an increased risk of in-hospital and post-discharge mortality.

Haloperidol primarily acts by blocking dopamine (D2) receptors. This dopamine blockade in the cerebral cortex improves cognition and reduces delirium. Along with the dopamine blockade, haloperidol has anti-inflammatory properties. It inhibits production of lipopolysaccharide induced pro-inflammatory cytokines, interleukin (IL-1) and tumor necrosis factor alpha (TNF-α). Haloperidol also increases levels of Interleukin -1 receptor antagonist (IL-1RA), an anti-inflammatory cytokine that blocks the action of other pro-inflammatory cytokines. If unchecked, the inflammatory cytokines cause impaired concentration, sleep disturbances, and agitation the cardinal symptoms of delirium; and induce a reduction in cholinergic activity. Given the inhibitory effect of acetylcholine on certain cytokines such as interleukin-6, a repetitive cycle of inadequate regulation of inflammation due to cholinergic depletion ensues. Haloperidol with its anti-inflammatory properties seeks to mitigate this repetitive vicious cycle.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 135 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Preventing Post-Operative Delirium in Pneumonectomy, Esophagectomy and Thoracotomy Patients
• Study Start Date: September 2013
• Actual Primary Completion Date: December 2015
• Actual Study Completion Date: December 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Haloperidol; Randomized patients will receive 0.5mg Haloperidol immediately after surgery and Q8H following the initial dose for a total of 4 days.	Drug: Haloperidol; 0.5mg IV Push immediately after surgery and Q8H following for a total of 4 days
Placebo Comparator: Placebo; Randomized patients will receive a placebo solution immediately after surgery and Q8H following for a total of 4 days.	Drug: Placebo

Outcome Measures

Primary Outcome Measures :

1. Efficacy of Low-dose Haloperidol in Reducing Delirium Incidence [ Time Frame: Up to 30 days ]
   Test the efficacy of low dose haloperidol in reducing delirium incidence among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo.

Secondary Outcome Measures :

1. Efficacy of Low-dose Haloperidol in Reducing Days With Delirium [ Time Frame: Up to 30 days ]
   Test the efficacy of low dose haloperidol in reducing the number of days with delirium among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo.
2. Efficacy of Low-dose Haloperidol in Reducing ICU and Hospital Length of Stay [ Time Frame: Date of hospital admission through date of hospital discharge, up to 3 weeks on average. ]
   Test the efficacy of low dose haloperidol in reducing ICU and hospital length of stay among patients who are status post esophagectomy or pneumonectomy compared to placebo.
3. Efficacy of Low-dose Haloperidol in Reducing Cognitive Impairment at Post-operative Follow-up [ Time Frame: Up to 3 months after hospital discharge on average. ]
   Test the efficacy of low dose haloperidol in reducing cognitive impairment at post-operative follow-up among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo. Cognitive status is assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The RBANS measures attention, language, visuospatial/constructional abilities, and memory. It is made up of 12 subtests. The subtests produce 5 index scores and a total scale score. All the subtest scores are summed to calculate a Total Index score. The Total Index score is presented. The Total Index score scale is from 0-100 with higher scores indicating less cognitive impairment.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. At least ≥ 18 years of age and older
2. Undergoing a possible or scheduled thoracotomy
3. English speaking

Exclusion Criteria:

1. History of Schizophrenia and Parkinson's disease
2. History of Severe Dementia
3. History of Alcohol Abuse
4. On Cholinesterase Inhibitors or Levodopa
5. Pregnant or Nursing
6. Corrected QT interval > 550 milliseconds at the time of randomization
7. History of Neuroleptic Malignant Syndrome or Haloperidol Allergy

Contacts and Locations

Locations

United States, Indiana

University Hospital

Indianapolis, Indiana, United States, 46202

Sponsors and Collaborators

Indiana University

Investigators

• Principal Investigator: Babar A Khan, MD, MS; Regenstrief Institute, Inc.
• Principal Investigator: Kenneth A Kesler, MD; IU School of Medicine

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Khan BA, Perkins AJ, Campbell NL, Gao S, Khan SH, Wang S, Fuchita M, Weber DJ, Zarzaur BL, Boustani MA, Kesler K. Preventing Postoperative Delirium After Major Noncardiac Thoracic Surgery-A Randomized Clinical Trial. J Am Geriatr Soc. 2018 Dec;66(12):2289-2297. doi: 10.1111/jgs.15640. Epub 2018 Nov 21.

• Responsible Party: Babar Khan, MD, MS, Principle Investigator, Regenstrief Institute, Inc.
• ClinicalTrials.gov Identifier: NCT02213900 History of Changes
• Other Study ID Numbers: VFR-398-Khan
• First Posted: August 12, 2014
• Results First Posted: April 13, 2017
• Last Update Posted: April 13, 2017
• Last Verified: March 2017

Keywords provided by Babar Khan, MD, MS, Regenstrief Institute, Inc.:

delirium; confusion; surgery; cognitive Impairment; post-traumatic Stress disorder; depression; anxiety

Additional relevant MeSH terms:

Delirium; Depression; Cognitive Dysfunction; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Behavioral Symptoms; Mental Disorders; Cognition Disorders; Neurocognitive Disorders; Trauma and Stressor Related Disorders; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Haloperidol; Haloperidol decanoate; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Dopamine Antagonists; Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action