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Pharmacological Management of Delirium (PMD)

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ClinicalTrials.gov Identifier: NCT00842608
Recruitment Status : Completed
First Posted : February 12, 2009
Results First Posted : March 24, 2017
Last Update Posted : August 17, 2018
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
MALAZ BOUSTANI, Regenstrief Institute, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Delirium
Cognitive Impairment
Interventions Behavioral: Reduced exposure to anticholinergics
Procedure: Reduced exposure to benzodiazepines
Drug: Haloperidol
Procedure: Usual care
Enrollment 551
Recruitment Details  
Pre-assignment Details 551 patients were consented into the study. After completing the consent and randomization, 6 patients withdrew from the study and were included in intention-to-treat analysis. 545 patients completed the protocol.
Arm/Group Title Haloperidol Eligible Intervention Haloperidol Eligible Usual Care Haldol-Ineligible Arm Haldol Ineligible Usual Care
Hide Arm/Group Description

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

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

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

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

Usual care

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

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

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

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

Usual Care

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

Period Title: Overall Study
Started 174 177 99 101
Completed 170 176 99 100
Not Completed 4 1 0 1
Arm/Group Title Haloperidol Eligible Intervention Haloperidol Eligible Usual Care Haldol-Ineligible Arm Haldol Ineligible Usual Care Total
Hide Arm/Group Description

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

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

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

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

Usual care

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

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

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

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

Usual Care

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

Total of all reporting groups
Overall Number of Baseline Participants 174 177 99 101 551
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 174 participants 177 participants 99 participants 101 participants 551 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
112
  64.4%
114
  64.4%
57
  57.6%
59
  58.4%
342
  62.1%
>=65 years
62
  35.6%
63
  35.6%
42
  42.4%
42
  41.6%
209
  37.9%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 174 participants 177 participants 99 participants 101 participants 551 participants
Female
98
  56.3%
86
  48.6%
65
  65.7%
53
  52.5%
302
  54.8%
Male
76
  43.7%
91
  51.4%
34
  34.3%
48
  47.5%
249
  45.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 174 participants 177 participants 99 participants 101 participants 551 participants
174 177 99 101 551
1.Primary Outcome
Title Days Free of Delirium and Coma
Hide Description [Not Specified]
Time Frame Admission through day 8 of stay
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Haloperidol Eligible Intervention Haloperidol Eligible Usual Care Haldol-Ineligible Arm Haldol Ineligible Usual Care
Hide Arm/Group Description:

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

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

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

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

Usual care

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

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

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

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

Usual Care

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

Overall Number of Participants Analyzed 174 177 99 101
Median (Inter-Quartile Range)
Unit of Measure: days
4
(2 to 7)
5
(1 to 7)
4
(1 to 7)
5
(2 to 7)
2.Secondary Outcome
Title Hospital Length of Stay Post Randomization
Hide Description [Not Specified]
Time Frame Participants were followed for the duration of hospital stay, an average of 11 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Haloperidol Eligible Intervention Haloperidol Eligible Usual Care Haldol-Ineligible Arm Haldol Ineligible Usual Care
Hide Arm/Group Description:

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

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

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

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

Usual care

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

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

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

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

Usual Care

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

Overall Number of Participants Analyzed 174 177 99 101
Mean (Standard Deviation)
Unit of Measure: days
20.2  (33.5) 18.6  (31.6) 18.8  (17.1) 14.9  (11.8)
3.Secondary Outcome
Title Mortality
Hide Description [Not Specified]
Time Frame ICU, in-hospital, 30-days post hospitalization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Haloperidol Eligible Intervention Haloperidol Eligible Usual Care Haldol-Ineligible Arm Haldol Ineligible Usual Care
Hide Arm/Group Description:

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

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

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

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

Usual care

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

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

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

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

Usual Care

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

Overall Number of Participants Analyzed 174 177 99 101
Measure Type: Count of Participants
Unit of Measure: Participants
20
  11.5%
32
  18.1%
11
  11.1%
8
   7.9%
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Haloperidol Eligible Intervention Haloperidol Eligible Usual Care Haldol-Ineligible Arm Haldol Ineligible Usual Care
Hide Arm/Group Description

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

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

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

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

Usual care

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

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

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

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

Usual Care

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

All-Cause Mortality
Haloperidol Eligible Intervention Haloperidol Eligible Usual Care Haldol-Ineligible Arm Haldol Ineligible Usual Care
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Haloperidol Eligible Intervention Haloperidol Eligible Usual Care Haldol-Ineligible Arm Haldol Ineligible Usual Care
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   45/174 (25.86%)   57/177 (32.20%)   27/99 (27.27%)   22/101 (21.78%) 
Blood and lymphatic system disorders         
Patients with Hematologic  12/174 (6.90%)  14/177 (7.91%)  3/99 (3.03%)  3/101 (2.97%) 
Cardiac disorders         
Patients with Cardiovascular  14/174 (8.05%)  20/177 (11.30%)  10/99 (10.10%)  9/101 (8.91%) 
Endocrine disorders         
Patients with Endocrine  1/174 (0.57%)  1/177 (0.56%)  0/99 (0.00%)  0/101 (0.00%) 
Gastrointestinal disorders         
Patients with GI  6/174 (3.45%)  6/177 (3.39%)  3/99 (3.03%)  3/101 (2.97%) 
Hepatobiliary disorders         
Patients with Hepatic  4/174 (2.30%)  3/177 (1.69%)  0/99 (0.00%)  0/101 (0.00%) 
Investigations         
Other  7/174 (4.02%)  0/177 (0.00%)  4/99 (4.04%)  0/101 (0.00%) 
Musculoskeletal and connective tissue disorders         
Patients with Musculoskeletal  2/174 (1.15%)  1/177 (0.56%)  1/99 (1.01%)  1/101 (0.99%) 
Nervous system disorders         
Patients with CNS  5/174 (2.87%)  7/177 (3.95%)  4/99 (4.04%)  2/101 (1.98%) 
Renal and urinary disorders         
Patients with GU  7/174 (4.02%)  4/177 (2.26%)  0/99 (0.00%)  4/101 (3.96%) 
Respiratory, thoracic and mediastinal disorders         
Patients with Respiratory  23/174 (13.22%)  31/177 (17.51%)  11/99 (11.11%)  12/101 (11.88%) 
Skin and subcutaneous tissue disorders         
Patients with Skin  2/174 (1.15%)  2/177 (1.13%)  1/99 (1.01%)  0/101 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Haloperidol Eligible Intervention Haloperidol Eligible Usual Care Haldol-Ineligible Arm Haldol Ineligible Usual Care
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   87/174 (50.00%)   82/177 (46.33%)   63/99 (63.64%)   59/101 (58.42%) 
General disorders         
General Events  87/174 (50.00%)  82/177 (46.33%)  63/99 (63.64%)  59/101 (58.42%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Malaz Boustani
Organization: Regenstrief Institute, Inc.
Phone: (317) 274-9235
Responsible Party: MALAZ BOUSTANI, Regenstrief Institute, Inc.
ClinicalTrials.gov Identifier: NCT00842608     History of Changes
Other Study ID Numbers: IA0145
R01AG034205 ( U.S. NIH Grant/Contract )
First Submitted: February 10, 2009
First Posted: February 12, 2009
Results First Submitted: November 11, 2016
Results First Posted: March 24, 2017
Last Update Posted: August 17, 2018