DeliriumPMDNCT00842608
Pharmacological Management of Delirium
A study testing Reduced exposure to anticholinergics, Reduced exposure to benzodiazepines and Haloperidol in people with Delirium and Cognitive Impairment, run by Indiana University at 3 sites in United States.
Trial summary
The purpose of this study is to develop and test the feasibility of using a specific pharmacological protocol to reduce delirium burden among older adults in the Intensive Care Unit (ICU). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Delirium, Cognitive Impairment
- What is being tested?
- Reduced exposure to anticholinergics, Reduced exposure to benzodiazepines and Haloperidol
- Type of treatment
- Pill or oral medicine, Surgery or procedure, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 551 participants
- Where
- 3 sitesUnited States
- Study dates
- Feb 2009to Jul 2015
- Phase
- Interventional
- 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
- 18 years of age or older
- Hospitalized on an ICU ward
- Delirium based on the RASS and the CAM-ICU assessments at any day during ICU stay
- English speaking
Who cannot join
- Admitted directly to a regular non-ICU ward
- Previously enrolled in the study
- Not eligible for delirium assessment as determined by RASS scores
- Prior history of severe mental illness
- Alcohol-related delirium
- Pregnant or nursing
- Have had an aphasic stroke
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Eskenazi Hospital
Indianapolis, Indiana, 46202
Methodist Hospital
Indianapolis, Indiana, 46202
University Hospital
Indianapolis, Indiana, 46202
About this study
The purpose of this study is to develop and test the feasibility of using a specific pharmacological protocol to reduce delirium burden among older adults in the Intensive Care Unit (ICU). The study will test the efficacy of a pharmacological intervention in reducing delirium severity and duration as well as length of stay and mortality compared to usual care.
Read the detailed description
In 2005, approximately 2.7 million Americans aged 65 and older spent at least one day in the intensive care unit (ICU), costing Medicare an estimated $27.5 billion. It is estimated that while hospitalized, up to 80% of these older ICU patients had delirium, an acute brain failure that is an independent predictor of morbidity and mortality which often goes unrecognized. Older adults with delirium are more prone to falls, injuries, pressure ulcers and restraints, complications which may also contribute to prolonged ICU and hospital length of stay, higher mortality rates, poorer functional status, limited rehabilitation, increased institutionalization, and higher health care costs. The literature supports treatment with a combination of a reduction in the use of benzodiazepines and anticholinergics and the use of low-dose neuroleptics such as haloperidol. However, there have been no randomized controlled trials evaluating the efficacy of this approach on reducing delirium severity, duration, and complications.
Building upon the e-CHAMP study, ("Enhancing Care for Hospitalized Older Adults With Memory Problems;" see NCT00182832), a recently completed quality improvement project tested the effectiveness of cognitive screening coupled with computerized decision support in reducing delirium and other hospital-related complications among 424 older adults hospitalized on the medical wards, which found that many of the older adults entering the study had already experienced delirium in the ICU prior to their transfer to the wards. This study will test a pharmacologic intervention that allows a more targeted approach to the care of older adults with delirium while still recognizing the clinicians' role in controlling symptoms and providing intensive care.
The hypothesis is that patients in the intervention arm as compared to usual care will have:
- reduced delirium severity, as measured by the Delirium Rating Scale (DRS-R-98), at one week following randomization or hospital discharge
- fewer hospital days with delirium or coma as determined by the Confusion Assessment Method in the ICU (CAM-ICU)
- shorter hospital lengths of stay
- lower ICU, hospital, and 30-day mortality
- Conditions
- Delirium, Cognitive Impairment
- Being tested
- Reduced exposure to anticholinergics, Reduced exposure to benzodiazepines, Haloperidol, Usual care
- Keywords
- confusion, dementia
- Medical subject headings
- Delirium, Cognitive Dysfunction, Confusion, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Reduced exposure to anticholinergicsBehavioural
Using the computerized support, physicians will be notified if they attempt to prescribe a patient a medication with anticholinergic properties and will be given a safe alternative to the drug.
Patients who are in the non-haldol arm will have their medical records manually reviewed by the study pharmacist as the computerized support is not set to differentiate between patients who can \& cannot receive Haldol
Reduced exposure to benzodiazepinesProcedure or surgery
Tapering exposure to benzodiazepines by 50% over the first 48 hours after mechanical ventilation, complete stop by discharge; no benzodiazepine orders for patients not requiring mechanical ventilation
HaloperidolDrug
Also called Haldol
0.5 to 1 mg haloperidol every 8 hours via oral or parenteral route for a total of seven days or until discharge from the hospital
Usual careProcedure or surgery
May include use of typical and atypical neuroleptics, benzodiazepines, and other sedatives to manage the symptoms of delirium
| Study group | Role | What they receive |
|---|---|---|
| Haloperidol Eligible Intervention | Experimental | 0.5-1mg Haloperidol Q8h for 7 days, reduced exposure to anticholinergics, reduced exposure to benzodiazepines Receives: Behavioral: Reduced exposure to anticholinergics; Procedure: Reduced exposure to benzodiazepines; Drug: Haloperidol |
| Haloperidol Eligible Usual Care | Active comparator | Usual care Receives: Procedure: Usual care |
| Haldol-Ineligible Arm | Experimental | Haldol-Ineligible arm for patients with contraindications for Haldol, unresolvable prolonged QTc, history of torsades de pointes, or history of seizures.
Patients are randomized and will still receive:
reduced exposure to anticholinergics, reduced exposure to benzodiazepines Receives: Behavioral: Reduced exposure to anticholinergics; Procedure: Reduced exposure to benzodiazepines |
| Haldol Ineligible Usual Care | Active comparator | Usual Care Receives: Procedure: Usual care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Days Free of Delirium and Coma
Measured: Admission through day 8 of stay
Secondary outcomes (2)
Hospital Length of Stay Post Randomization
Measured: Participants were followed for the duration of hospital stay, an average of 11 days
Mortality
Measured: ICU, in-hospital, 30-days post hospitalization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2009 (estimated)
- Study startFeb 2009
- Primary completionJul 2015
- Study completionJul 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 (5)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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 551 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Principal investigator, MALAZ BOUSTANI, Regenstrief Institute, Inc.
- Investigators
- Malaz Boustani, MD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00842608
- Sponsor's protocol ID
- IA0145
- Other IDs
- R01AG034205
- Acronym
- PMD
- Status last verified
- Aug 2018
- First submitted
- 10 Feb 2009
- Last updated
- 17 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Wang S, Perkins AJ, Chi R, Yates BA, Khan SH, Gao S, Boustani M, Khan BA. Risk factors for dementia in older intensive care unit (ICU) survivors. Alzheimers Dement. 2024 Jan;20(1):278-287. doi: 10.1002/alz.13423. Epub 2023 Aug 17.
PubMed 37589315Ortiz D, Lindroth HL, Braly T, Perkins AJ, Mohanty S, Meagher AD, Khan SH, Boustani MA, Khan BA. Delirium severity does not differ between medical and surgical intensive care units after adjusting for medication use. Sci Rep. 2022 Aug 24;12(1):14447. doi: 10.1038/s41598-022-18429-9.
PubMed 36002562Lindroth H, Khan BA, Carpenter JS, Gao S, Perkins AJ, Khan SH, Wang S, Jones RN, Boustani MA. Delirium Severity Trajectories and Outcomes in ICU Patients. Defining a Dynamic Symptom Phenotype. Ann Am Thorac Soc. 2020 Sep;17(9):1094-1103. doi: 10.1513/AnnalsATS.201910-764OC.
PubMed 32383964Khan BA, Perkins AJ, Campbell NL, Gao S, Farber MO, Wang S, Khan SH, Zarzaur BL, Boustani MA. Pharmacological Management of Delirium in the Intensive Care Unit: A Randomized Pragmatic Clinical Trial. J Am Geriatr Soc. 2019 May;67(5):1057-1065. doi: 10.1111/jgs.15781. Epub 2019 Jan 25.
PubMed 30681720Campbell NL, Khan BA, Farber M, Campbell T, Perkins AJ, Hui SL, Abernathy G, Buckley J, Sing R, Tricker J, Zawahiri M, Boustani MA. Improving delirium care in the intensive care unit: the design of a pragmatic study. Trials. 2011 Jun 6;12:139. doi: 10.1186/1745-6215-12-139.
PubMed 21645330
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacological Management of Delirium
- ClinicalTrials.gov ID
- NCT00842608
- Acronym / sponsor ID
- PMD / IA0145
- Conditions
- Delirium, Cognitive Impairment
- Keywords
- confusion, dementia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 551 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- Feb 2009
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 12 Feb 2009 (estimated)
- Results
- Posted 24 Mar 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 develop and test the feasibility of using a specific pharmacological protocol to reduce delirium burden among older adults in the Intensive Care Unit (ICU). The study will test the efficacy of a pharmacological intervention in reducing delirium severity and duration as well as length of stay and mortality compared to usual care.
Detailed description
In 2005, approximately 2.7 million Americans aged 65 and older spent at least one day in the intensive care unit (ICU), costing Medicare an estimated $27.5 billion. It is estimated that while hospitalized, up to 80% of these older ICU patients had delirium, an acute brain failure that is an independent predictor of morbidity and mortality which often goes unrecognized. Older adults with delirium are more prone to falls, injuries, pressure ulcers and restraints, complications which may also contribute to prolonged ICU and hospital length of stay, higher mortality rates, poorer functional status, limited rehabilitation, increased institutionalization, and higher health care costs. The literature supports treatment with a combination of a reduction in the use of benzodiazepines and anticholinergics and the use of low-dose neuroleptics such as haloperidol. However, there have been no randomized controlled trials evaluating the efficacy of this approach on reducing delirium severity, duration, and complications.
Building upon the e-CHAMP study, ("Enhancing Care for Hospitalized Older Adults With Memory Problems;" see NCT00182832), a recently completed quality improvement project tested the effectiveness of cognitive screening coupled with computerized decision support in reducing delirium and other hospital-related complications among 424 older adults hospitalized on the medical wards, which found that many of the older adults entering the study had already experienced delirium in the ICU prior to their transfer to the wards. This study will test a pharmacologic intervention that allows a more targeted approach to the care of older adults with delirium while still recognizing the clinicians' role in controlling symptoms and providing intensive care.
The hypothesis is that patients in the intervention arm as compared to usual care will have:
- reduced delirium severity, as measured by the Delirium Rating Scale (DRS-R-98), at one week following randomization or hospital discharge
- fewer hospital days with delirium or coma as determined by the Confusion Assessment Method in the ICU (CAM-ICU)
- shorter hospital lengths of stay
- lower ICU, hospital, and 30-day mortality
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Haloperidol Eligible Intervention | Experimental | Behavioral: Reduced exposure to anticholinergics, Procedure: Reduced exposure to benzodiazepines, Drug: Haloperidol0.5-1mg Haloperidol Q8h for 7 days, reduced exposure to anticholinergics, reduced exposure to benzodiazepines |
| Haloperidol Eligible Usual Care | Active comparator | Procedure: Usual careUsual care |
| Haldol-Ineligible Arm | Experimental | Behavioral: Reduced exposure to anticholinergics, Procedure: Reduced exposure to benzodiazepinesHaldol-Ineligible arm for patients with contraindications for Haldol, unresolvable prolonged QTc, history of torsades de pointes, or history of seizures. Patients are randomized and will still receive: reduced exposure to anticholinergics, reduced exposure to benzodiazepines |
| Haldol Ineligible Usual Care | Active comparator | Procedure: Usual careUsual Care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 18 years of age or older
- Hospitalized on an ICU ward
- Delirium based on the RASS and the CAM-ICU assessments at any day during ICU stay
- English speaking
Key exclusion criteria (7 listed)
- Admitted directly to a regular non-ICU ward
- Previously enrolled in the study
- Not eligible for delirium assessment as determined by RASS scores
- Prior history of severe mental illness
- Alcohol-related delirium
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 |
|---|---|---|
| Reduced exposure to anticholinergicsUsing the computerized support, physicians will be notified if they attempt to prescribe a patient a medication with anticholinergic properties and will be given a safe alternative to the drug. Patients who are in the non-haldol arm will have their medical records manually reviewed by the study pharmacist as the computerized support is not set to differentiate between patients who can \& cannot receive Haldol | Behavioural | Haldol-Ineligible Arm, Haloperidol Eligible Intervention |
| Reduced exposure to benzodiazepinesTapering exposure to benzodiazepines by 50% over the first 48 hours after mechanical ventilation, complete stop by discharge; no benzodiazepine orders for patients not requiring mechanical ventilation | Procedure or surgery | Haldol-Ineligible Arm, Haloperidol Eligible Intervention |
| HaloperidolAlso: Haldol0.5 to 1 mg haloperidol every 8 hours via oral or parenteral route for a total of seven days or until discharge from the hospital | Drug | Haloperidol Eligible Intervention |
| Usual careMay include use of typical and atypical neuroleptics, benzodiazepines, and other sedatives to manage the symptoms of delirium | Procedure or surgery | Haldol Ineligible Usual Care, Haloperidol Eligible Usual Care |
Primary outcome
Days Free of Delirium and Coma
Time frame: Admission through day 8 of stay
2 secondary outcomes
Hospital Length of Stay Post Randomization
Time frame: Participants were followed for the duration of hospital stay, an average of 11 days
Mortality
Time frame: ICU, in-hospital, 30-days post hospitalization
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37589315Wang S, Perkins AJ, Chi R, Yates BA, Khan SH, Gao S, Boustani M, Khan BA. Risk factors for dementia in older intensive care unit (ICU) survivors. Alzheimers Dement. 2024 Jan;20(1):278-287. doi: 10.1002/alz.13423. Epub 2023 Aug 17.
- Derived from this study: PubMed 36002562Ortiz D, Lindroth HL, Braly T, Perkins AJ, Mohanty S, Meagher AD, Khan SH, Boustani MA, Khan BA. Delirium severity does not differ between medical and surgical intensive care units after adjusting for medication use. Sci Rep. 2022 Aug 24;12(1):14447. doi: 10.1038/s41598-022-18429-9.
- Derived from this study: PubMed 32383964Lindroth H, Khan BA, Carpenter JS, Gao S, Perkins AJ, Khan SH, Wang S, Jones RN, Boustani MA. Delirium Severity Trajectories and Outcomes in ICU Patients. Defining a Dynamic Symptom Phenotype. Ann Am Thorac Soc. 2020 Sep;17(9):1094-1103. doi: 10.1513/AnnalsATS.201910-764OC.
- Derived from this study: PubMed 30681720Khan BA, Perkins AJ, Campbell NL, Gao S, Farber MO, Wang S, Khan SH, Zarzaur BL, Boustani MA. Pharmacological Management of Delirium in the Intensive Care Unit: A Randomized Pragmatic Clinical Trial. J Am Geriatr Soc. 2019 May;67(5):1057-1065. doi: 10.1111/jgs.15781. Epub 2019 Jan 25.
- Derived from this study: PubMed 21645330Campbell NL, Khan BA, Farber M, Campbell T, Perkins AJ, Hui SL, Abernathy G, Buckley J, Sing R, Tricker J, Zawahiri M, Boustani MA. Improving delirium care in the intensive care unit: the design of a pragmatic study. Trials. 2011 Jun 6;12:139. doi: 10.1186/1745-6215-12-139.
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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.
Malaz Boustani, MD principal investigator
Indiana University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Reduced exposure to anticholinergics, Reduced exposure to benzodiazepines and Haloperidol in people with Delirium and Cognitive Impairment, run by Indiana University at 3 sites 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 4 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 17 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Mar 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?
Days Free of Delirium and Coma (time frame: Admission through day 8 of stay). 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 NCT00842608, which also lists 5 linked publications.
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 17 Aug 2018.