Pharmacological Management of Delirium

NCT ID: NCT00842608

Last Updated: 2018-08-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 551 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-02-28
• Study Completion Date: 2015-07-31

Brief 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). 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

Conditions

Delirium; Cognitive Impairment

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Haloperidol Eligible Intervention

0.5-1mg Haloperidol Q8h for 7 days, reduced exposure to anticholinergics, reduced exposure to benzodiazepines

Group Type: EXPERIMENTAL

Reduced exposure to anticholinergics

Intervention Type: BEHAVIORAL

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 benzodiazepines

Intervention Type: PROCEDURE

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

Haloperidol

Intervention Type: DRUG

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

Haloperidol Eligible Usual Care

Usual care

Group Type: ACTIVE_COMPARATOR

Usual care

Intervention Type: PROCEDURE

May include use of typical and atypical neuroleptics, benzodiazepines, and other sedatives to manage the symptoms of delirium

Haldol-Ineligible Arm

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

Group Type: EXPERIMENTAL

Reduced exposure to anticholinergics

Intervention Type: BEHAVIORAL

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 benzodiazepines

Intervention Type: PROCEDURE

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

Haldol Ineligible Usual Care

Usual Care

Group Type: ACTIVE_COMPARATOR

Usual care

Intervention Type: PROCEDURE

May include use of typical and atypical neuroleptics, benzodiazepines, and other sedatives to manage the symptoms of delirium

Interventions

Reduced exposure to anticholinergics

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

Intervention Type: BEHAVIORAL

Reduced exposure to benzodiazepines

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

Intervention Type: PROCEDURE

Haloperidol

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

Intervention Type: DRUG

Usual care

May include use of typical and atypical neuroleptics, benzodiazepines, and other sedatives to manage the symptoms of delirium

Intervention Type: PROCEDURE

Other Intervention Names

Haldol

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

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

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

MALAZ BOUSTANI

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Malaz Boustani, MD

Role: PRINCIPAL_INVESTIGATOR

Indiana University School of Medicine

Locations

Eskenazi Hospital

Indianapolis, Indiana, United States

Methodist Hospital

Indianapolis, Indiana, United States

University Hospital

Indianapolis, Indiana, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 37589315 (View on PubMed)

Ortiz 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.

Reference Type: DERIVED

PMID: 36002562 (View on PubMed)

Lindroth 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.

Reference Type: DERIVED

PMID: 32383964 (View on PubMed)

Khan 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.

Reference Type: DERIVED

PMID: 30681720 (View on PubMed)

Campbell 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.

Reference Type: DERIVED

PMID: 21645330 (View on PubMed)

Other Identifiers

R01AG034205

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IA0145

Identifier Type: -

Identifier Source: org_study_id