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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Haloperidol | Experimental | Randomized patients will receive 0.5mg Haloperidol immediately after surgery and Q8H following the initial dose for a total of 4 days. |
|
| Placebo | Placebo Comparator | Randomized patients will receive a placebo solution immediately after surgery and Q8H following for a total of 4 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Haloperidol | Drug | 0.5mg IV Push immediately after surgery and Q8H following for a total of 4 days |
|
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of Low-dose Haloperidol in Reducing Delirium Incidence | Test the efficacy of low dose haloperidol in reducing delirium incidence among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo. | Up to 30 days |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of Low-dose Haloperidol in Reducing Days With Delirium | 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. | Up to 30 days |
| Efficacy of Low-dose Haloperidol in Reducing ICU and Hospital Length of Stay |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Babar A Khan, MD, MS | Regenstrief Institute, Inc. | Principal Investigator |
| Kenneth A Kesler, MD | IU School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital | Indianapolis | Indiana | 46202 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30460981 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Haloperidol | Randomized patients will receive 0.5mg Haloperidol immediately after surgery and Q8H following the initial dose for a total of 4 days. Haloperidol: 0.5mg IV Push immediately after surgery and Q8H following for a total of 4 days |
| FG001 | Placebo | Randomized patients will receive a placebo solution immediately after surgery and Q8H following for a total of 4 days. Placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Haloperidol | Randomized patients will receive 0.5mg Haloperidol immediately after surgery and Q8H following the initial dose for a total of 4 days. Haloperidol: 0.5mg IV Push immediately after surgery and Q8H following for a total of 4 days |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Efficacy of Low-dose Haloperidol in Reducing Delirium Incidence | Test the efficacy of low dose haloperidol in reducing delirium incidence among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo. | Posted | Count of Participants | Participants | Up to 30 days |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Haloperidol | Randomized patients will receive 0.5mg Haloperidol immediately after surgery and Q8H following the initial dose for a total of 4 days. Haloperidol: 0.5mg IV Push immediately after surgery and Q8H following for a total of 4 days |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Death | General disorders |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Babar Khan, MD | Indiana University | 317-274-9132 | bakhan@iu.edu |
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| ID | Term |
|---|---|
| D003693 | Delirium |
| D060825 | Cognitive Dysfunction |
| D013313 | Stress Disorders, Post-Traumatic |
| D003863 | Depression |
| D001008 | Anxiety Disorders |
| D003221 | Confusion |
| ID | Term |
|---|---|
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| D006220 | Haloperidol |
| ID | Term |
|---|---|
| D002090 | Butyrophenones |
| D007659 | Ketones |
| D009930 | Organic Chemicals |
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| Placebo | Drug |
|
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. |
| Date of hospital admission through date of hospital discharge, up to 3 weeks on average. |
| Efficacy of Low-dose Haloperidol in Reducing Cognitive Impairment at Post-operative Follow-up | 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. | Up to 3 months after hospital discharge on average. |
Randomized patients will receive a placebo solution immediately after surgery and Q8H following for a total of 4 days. Placebo |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
| Secondary | Efficacy of Low-dose Haloperidol in Reducing Days With Delirium | 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. | Posted | Mean | Standard Deviation | Days with Delirium | Up to 30 days |
|
|
|
| Secondary | Efficacy of Low-dose Haloperidol in Reducing ICU and Hospital Length of Stay | 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. | Posted | Mean | Standard Deviation | Days | Date of hospital admission through date of hospital discharge, up to 3 weeks on average. |
|
|
|
| Secondary | Efficacy of Low-dose Haloperidol in Reducing Cognitive Impairment at Post-operative Follow-up | 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. | Posted | Mean | Standard Deviation | Units on a scale | Up to 3 months after hospital discharge on average. |
|
|
|
| 3 |
| 68 |
| 0 |
| 68 |
| EG001 | Placebo | Randomized patients will receive a placebo solution immediately after surgery and Q8H following for a total of 4 days. Placebo | 2 | 67 | 0 | 67 |
| Life Threatening Episode | General disorders |
|
| Inpatient or Prolonged Current Hospitalization | General disorders | Could include significant incapacitation or an episode requiring intervention to prevent permanent impairment. |
|
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| D013568 | Pathological Conditions, Signs and Symptoms |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D003072 | Cognition Disorders |
| D040921 | Stress Disorders, Traumatic |
| D000068099 | Trauma and Stressor Related Disorders |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |