Trial Outcomes & Findings for Pharmacological Management of Delirium (NCT NCT00842608)

NCT ID: NCT00842608

Last Updated: 2018-08-17

Results Overview

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

551 participants

Primary outcome timeframe

Admission through day 8 of stay

Results posted on

2018-08-17

Participant Flow

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.

Participant milestones

Participant milestones
Measure
Haloperidol Eligible Intervention
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
Haloperidol Eligible Usual Care
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
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
Haldol Ineligible Usual Care
Usual Care Usual care: May include use of typical and atypical neuroleptics, benzodiazepines, and other sedatives to manage the symptoms of delirium
Overall Study
STARTED
174
177
99
101
Overall Study
COMPLETED
170
176
99
100
Overall Study
NOT COMPLETED
4
1
0
1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacological Management of Delirium

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Haloperidol Eligible Intervention
n=174 Participants
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
Haloperidol Eligible Usual Care
n=177 Participants
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
n=99 Participants
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
Haldol Ineligible Usual Care
n=101 Participants
Usual Care Usual care: May include use of typical and atypical neuroleptics, benzodiazepines, and other sedatives to manage the symptoms of delirium
Total
n=551 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
0 Participants
n=7 Participants
0 Participants
n=31 Participants
Age, Categorical
Between 18 and 65 years
112 Participants
n=99 Participants
114 Participants
n=107 Participants
57 Participants
n=206 Participants
59 Participants
n=7 Participants
342 Participants
n=31 Participants
Age, Categorical
>=65 years
62 Participants
n=99 Participants
63 Participants
n=107 Participants
42 Participants
n=206 Participants
42 Participants
n=7 Participants
209 Participants
n=31 Participants
Sex: Female, Male
Female
98 Participants
n=99 Participants
86 Participants
n=107 Participants
65 Participants
n=206 Participants
53 Participants
n=7 Participants
302 Participants
n=31 Participants
Sex: Female, Male
Male
76 Participants
n=99 Participants
91 Participants
n=107 Participants
34 Participants
n=206 Participants
48 Participants
n=7 Participants
249 Participants
n=31 Participants
Region of Enrollment
United States
174 participants
n=99 Participants
177 participants
n=107 Participants
99 participants
n=206 Participants
101 participants
n=7 Participants
551 participants
n=31 Participants

PRIMARY outcome

Timeframe: Admission through day 8 of stay

Outcome measures

Outcome measures
Measure
Haloperidol Eligible Intervention
n=174 Participants
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
Haloperidol Eligible Usual Care
n=177 Participants
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
n=99 Participants
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
Haldol Ineligible Usual Care
n=101 Participants
Usual Care Usual care: May include use of typical and atypical neuroleptics, benzodiazepines, and other sedatives to manage the symptoms of delirium
Days Free of Delirium and Coma
4 days
Interval 2.0 to 7.0
5 days
Interval 1.0 to 7.0
4 days
Interval 1.0 to 7.0
5 days
Interval 2.0 to 7.0

SECONDARY outcome

Timeframe: Participants were followed for the duration of hospital stay, an average of 11 days

Outcome measures

Outcome measures
Measure
Haloperidol Eligible Intervention
n=174 Participants
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
Haloperidol Eligible Usual Care
n=177 Participants
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
n=99 Participants
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
Haldol Ineligible Usual Care
n=101 Participants
Usual Care Usual care: May include use of typical and atypical neuroleptics, benzodiazepines, and other sedatives to manage the symptoms of delirium
Hospital Length of Stay Post Randomization
20.2 days
Standard Deviation 33.5
18.6 days
Standard Deviation 31.6
18.8 days
Standard Deviation 17.1
14.9 days
Standard Deviation 11.8

SECONDARY outcome

Timeframe: ICU, in-hospital, 30-days post hospitalization

Outcome measures

Outcome measures
Measure
Haloperidol Eligible Intervention
n=174 Participants
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
Haloperidol Eligible Usual Care
n=177 Participants
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
n=99 Participants
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
Haldol Ineligible Usual Care
n=101 Participants
Usual Care Usual care: May include use of typical and atypical neuroleptics, benzodiazepines, and other sedatives to manage the symptoms of delirium
Mortality
20 Participants
32 Participants
11 Participants
8 Participants

Adverse Events

Haloperidol Eligible Intervention

Serious events: 45 serious events
Other events: 87 other events
Deaths: 0 deaths

Haloperidol Eligible Usual Care

Serious events: 57 serious events
Other events: 82 other events
Deaths: 0 deaths

Haldol-Ineligible Arm

Serious events: 27 serious events
Other events: 63 other events
Deaths: 0 deaths

Haldol Ineligible Usual Care

Serious events: 22 serious events
Other events: 59 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Haloperidol Eligible Intervention
n=174 participants at risk
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
Haloperidol Eligible Usual Care
n=177 participants at risk
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
n=99 participants at risk
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
Haldol Ineligible Usual Care
n=101 participants at risk
Usual Care Usual care: May include use of typical and atypical neuroleptics, benzodiazepines, and other sedatives to manage the symptoms of delirium
Nervous system disorders
Patients with CNS
2.9%
5/174
4.0%
7/177
4.0%
4/99
2.0%
2/101
Cardiac disorders
Patients with Cardiovascular
8.0%
14/174
11.3%
20/177
10.1%
10/99
8.9%
9/101
Respiratory, thoracic and mediastinal disorders
Patients with Respiratory
13.2%
23/174
17.5%
31/177
11.1%
11/99
11.9%
12/101
Gastrointestinal disorders
Patients with GI
3.4%
6/174
3.4%
6/177
3.0%
3/99
3.0%
3/101
Renal and urinary disorders
Patients with GU
4.0%
7/174
2.3%
4/177
0.00%
0/99
4.0%
4/101
Skin and subcutaneous tissue disorders
Patients with Skin
1.1%
2/174
1.1%
2/177
1.0%
1/99
0.00%
0/101
Hepatobiliary disorders
Patients with Hepatic
2.3%
4/174
1.7%
3/177
0.00%
0/99
0.00%
0/101
Blood and lymphatic system disorders
Patients with Hematologic
6.9%
12/174
7.9%
14/177
3.0%
3/99
3.0%
3/101
Endocrine disorders
Patients with Endocrine
0.57%
1/174
0.56%
1/177
0.00%
0/99
0.00%
0/101
Musculoskeletal and connective tissue disorders
Patients with Musculoskeletal
1.1%
2/174
0.56%
1/177
1.0%
1/99
0.99%
1/101
Investigations
Other
4.0%
7/174
0.00%
0/177
4.0%
4/99
0.00%
0/101

Other adverse events

Other adverse events
Measure
Haloperidol Eligible Intervention
n=174 participants at risk
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
Haloperidol Eligible Usual Care
n=177 participants at risk
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
n=99 participants at risk
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
Haldol Ineligible Usual Care
n=101 participants at risk
Usual Care Usual care: May include use of typical and atypical neuroleptics, benzodiazepines, and other sedatives to manage the symptoms of delirium
General disorders
General Events
50.0%
87/174
46.3%
82/177
63.6%
63/99
58.4%
59/101

Additional Information

Dr. Malaz Boustani

Regenstrief Institute, Inc.

Phone: (317) 274-9235

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place