DeliriumPhase 4PE-PODNCT02213900
Preventing Post-Operative Delirium in Patients Undergoing a Pneumonectomy, Esophagectomy or Thoracotomy
A Phase 4 study testing Haloperidol in people with Delirium and Cognitive Impairment, run by Indiana University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Delirium, Cognitive Impairment, Post-traumatic Stress Disorder
- What is being tested?
- Haloperidol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 135 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2013to Dec 2015
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- At least ≥ 18 years of age and older
- Undergoing a possible or scheduled thoracotomy
- English speaking
Who cannot join
- History of Schizophrenia and Parkinson's disease
- History of Severe Dementia
- History of Alcohol Abuse
- On Cholinesterase Inhibitors or Levodopa
- Pregnant or Nursing
- Corrected QT interval > 550 milliseconds at the time of randomization
- History of Neuroleptic Malignant Syndrome or Haloperidol Allergy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Preventing Post-Operative Delirium in Pneumonectomy, Esophagectomy and Thoracotomy Patients
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.
Read the 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.
- Being tested
- Haloperidol, Placebo
- Keywords
- delirium, confusion, surgery, cognitive Impairment, post-traumatic Stress disorder, depression, anxiety
- Medical subject headings
- Delirium, Cognitive Dysfunction, Stress Disorders, Post-Traumatic, Depression, Anxiety Disorders, Confusion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HaloperidolDrug
0.5mg IV Push immediately after surgery and Q8H following for a total of 4 days
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Haloperidol | Experimental | Randomized patients will receive 0.5mg Haloperidol immediately after surgery and Q8H following the initial dose for a total of 4 days. Receives: Drug: Haloperidol |
| Placebo | Placebo comparator | Randomized patients will receive a placebo solution immediately after surgery and Q8H following for a total of 4 days. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 30 days
Secondary outcomes (3)
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.
Measured: Up to 30 days
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.
Measured: 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.
Measured: Up to 3 months after hospital discharge on average.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2014 (estimated)
- Study startSep 2013
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for DeliriumStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 135 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Babar Khan, MD, MS, Regenstrief Institute, Inc.
- Investigators
- Babar A Khan, MD, MS, Principal investigator, Regenstrief Institute, Inc.Kenneth A Kesler, MD, Principal investigator, IU School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02213900
- Sponsor's protocol ID
- VFR-398-Khan
- Acronym
- PE-POD
- Status last verified
- Mar 2017
- First submitted
- 18 Mar 2014
- Last updated
- 13 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 30460981
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preventing Post-Operative Delirium in Pneumonectomy, Esophagectomy and Thoracotomy Patients
- ClinicalTrials.gov ID
- NCT02213900
- Acronym / sponsor ID
- PE-POD / VFR-398-Khan
- Keywords
- delirium, confusion, surgery, cognitive Impairment, post-traumatic Stress disorder, depression, anxiety
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 135 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Study start
- Sep 2013
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 12 Aug 2014 (estimated)
- Results
- Posted 13 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Haloperidol | Experimental | Drug: HaloperidolRandomized patients will receive 0.5mg Haloperidol immediately after surgery and Q8H following the initial dose for a total of 4 days. |
| Placebo | Placebo comparator | Drug: PlaceboRandomized patients will receive a placebo solution immediately after surgery and Q8H following for a total of 4 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- At least ≥ 18 years of age and older
- Undergoing a possible or scheduled thoracotomy
- English speaking
Key exclusion criteria (7 listed)
- History of Schizophrenia and Parkinson's disease
- History of Severe Dementia
- History of Alcohol Abuse
- On Cholinesterase Inhibitors or Levodopa
- Pregnant or Nursing
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Haloperidol0.5mg IV Push immediately after surgery and Q8H following for a total of 4 days | Drug | Haloperidol |
| Placebo | Drug | Placebo |
Primary outcome
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.
3 secondary outcomes
Efficacy of Low-dose Haloperidol in Reducing Days With Delirium
Time frame: Up to 30 days
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30460981Khan 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.
Related trials for Delirium
RecruitingObservational study
The Impact of Fast-Track Anesthesia on Postoperative Neurocognitive Function in Patients Undergoing Cardiac Surgery
Delirium - Postoperative, Cardiac Surgery
Active, not recruitingPhase 3
The Danish Out-of-Hospital Cardiac Arrest Study
Out-Of-Hospital Cardiac Arrest, Post-Cardiac Arrest Syndrome
Not yet recruiting
Prediction and Prevention of Postoperative Mortality and Morbidity
Dementia, Postoperative Delirium (POD)
Not yet recruiting
DEXmedetomidine for Postoperative Analgesia and Delirium Prevention After NEUROsurgery (DEX-NEURO Trial)
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Lactium Premedication to Prevent Emergence Agitation
Lactium, Premedication
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Babar A Khan, MD, MS principal investigator
Regenstrief Institute, Inc.
Kenneth A Kesler, MD principal investigator
IU School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Haloperidol in people with Delirium and Cognitive Impairment, run by Indiana University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of Low-dose Haloperidol in Reducing Delirium Incidence (time frame: Up to 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02213900, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2017; AzTrials last refreshed its copy on 7 Nov 2026.