The Modifying the Impact of ICU-Associated Neurological Dysfunction-USA (MIND-USA) Study

• Sponsor: Vanderbilt University Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01211522
• Collaborator: (none)
• Enrollment: 566
• Locations: 16
• Arms: 3
• Actual Duration (Months): 79.1
• Patients Per Site: 35.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The long-term objective of the MIND-USA (Modifying the Impact of ICU-Induced Neurological Dysfunction-USA) Study is to define the role of antipsychotics in the management of delirium in vulnerable critically ill patients. We and others have shown that delirium is an independent predictor of more death, longer stay, higher cost, and long-term cognitive impairment often commensurate with moderate dementia. The rapidly expanding aging ICU population is especially vulnerable to develop delirium, with 7 of 10 medical and surgical ICU patients developing this organ dysfunction. Antipsychotics are the first-line pharmacological agents recommended to treat delirium, and over the past 30 years they gained widespread use in hospitalized patients globally prior to adequate testing of efficacy and safety for this indication. Haloperidol, the most commonly chosen antipsychotic, is used by over 80% of ICU doctors for delirium, while atypical antipsychotics are prescribed by 40%. Antipsychotics safety concerns include lethal cardiac arrhythmias, extrapyramidal symptoms, and the highly publicized increased mortality associated with their use in non-ICU geriatric populations. The overarching hypothesis is that administration of typical and atypical antipsychotics-haloperidol and ziprasidone, in this case-to critically ill patients with delirium will improve short- and long-term clinical outcomes, including days alive without acute brain dysfunction (referred to as delirium/coma-free days or DCFDs) over a 14-day period; 30-day, 90-day, and 1-year survival; ICU length of stay; incidence, severity, and/or duration of long-term neuropsychological dysfunction; and quality of life at 90-day and 1-year. To test these hypotheses, the MIND-USA Study will be a multi-center, double-blind, randomized, placebo-controlled investigation in 561 critically ill, delirious medical/surgical ICU patients who are (a) on mechanical ventilation or non-invasive positive pressure ventilation or (b) in shock on vasopressors. In each group (haloperidol, ziprasidone, and placebo), 187 patients will be enrolled and treated until delirium has resolved for 48 hours or to 14 days (whichever occurs first) and followed for 1 year.

Condition or Disease	Intervention/Treatment	Phase
Delirium; Impaired Cognition; Long Term Psychologic Disorders	Drug: Haloperidol; Drug: Ziprasidone; Drug: Placebo	Phase 3

Detailed Description

The primary and secondary outcomes of the MIND-USA investigation will be analyzed both according to the individual comparisons by group of "haloperidol treated" vs. "placebo treated" and "ziprasidone treated" vs. "placebo treated" and also the combined grouping of both antipsychotics ("haloperidol plus ziprasidone treated" patients vs. "placebo treated" patients). In the latter third of the study, as a result of a paper by Patel S et al AJRCCM 2014 about rapidly reversible delirium (RRD), we considered modifying delirium assessments to detect those who might convert from CAM-ICU positive to negative following SATs, but we estimated that only 5 patients per arm would be in this category (and indeed <20 per arm in the entire study using the 10% rate published by Patel). With such low numbers and the assurance that through randomization we would have all groups analyzed similarly according to the study drug assignment, we elected not to alter the protocol and not to conduct subgroup analyses according to RRD status.

Study Design

• Study Type: Interventional
• Actual Enrollment: 566 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double blind, placebo controlled
• Primary Purpose: Treatment
• Official Title: MIND-USA Study: Modifying the Impact of ICU-Associated Neurological Dysfunction
• Actual Study Start Date: Dec 14, 2011
• Actual Primary Completion Date: Aug 28, 2017
• Actual Study Completion Date: Jul 19, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Haloperidol Haloperidol	Drug: Haloperidol; Haloperidol, up to 10mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 5mg/mL. Patient will only receive IV while in the ICU.; Other Names: Haldol
Experimental: Ziprasidone Ziprasidone	Drug: Ziprasidone; Ziprasidone, up to 20mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 10mg/mL. Patient will only receive IV while in the ICU.; Other Names: Geodon
Placebo Comparator: Placebo Placebo	Drug: Placebo; Placebo, up to 10mL q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes. Patient will only receive IV while in the ICU.

Outcome Measures

Primary Outcome Measures

1. Delirium/Coma-free Days (DCFDs) [14 days]

   Defined as the number of days during the 14-day intervention period (beginning on the day of randomization) that the patient was alive and experienced neither delirium nor coma.

Secondary Outcome Measures

1. Mortality [30-day and 90-day]

   Deaths within the specified timeframe

2. Delirium Duration [14 days]

   Duration of delirium during the intervention period

3. Number of Participants With Torsades de Pointes [14 days plus 4-day post-study drug period (if longer than 14 days)]

4. Number of Participants With Extrapyramidal Symptoms [14 days plus 4-day post-study drug period (if longer than 14 days)]

5. Number of Participants With Neuroleptic Malignant Syndrome [14 days plus 4-day post-study drug period (if longer than 14 days)]

6. Time to Liberation From Mechanical Ventilation [30 days]

   Days from randomization to successful liberation from mechanical ventilation, where "successful" indicates that liberation was followed by at least 48 hours alive and without reinitiation of invasive or noninvasive ventilation.

7. Time to Final ICU Discharge [90 days]

   Days from randomization to final, successful ICU discharge, where "successful" indicates that discharge was followed by at least 48 hours alive. "ICU discharge" is represented by readiness for ICU discharge indicated by a physician order for transfer to a lower level of care even if a bed availability problems prevent actual discharge from the ICU.

8. Time to ICU Readmission [90 days after first ICU discharge]

   Days from first ICU discharge to next ICU readmission.

9. Time to Hospital Discharge [90 days]

   Days from randomization to successful hospital discharge, where "successful" indicates that discharge was followed by at least 48 hours alive.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. adult patients (≥18 years old)

2. in a medical and/or surgical ICU

3. on mechanical ventilation or non-invasive positive pressure ventilation (NIPPV), and/or requiring vasopressors due to shock

4. delirious (according to the CAM-ICU)

Exclusion Criteria:

1. Rapidly resolving organ failure criteria, indicated by planned immediate discontinuation of mechanical ventilation, NIPPV, and/or vasopressors at the time of screening for study enrollment

2. Pregnancy or breastfeeding (negative pregnancy test required prior to enrollment of female patients of childbearing age)

3. Severe dementia or neurodegenerative disease, defined as either impairment that prevents the patient from living independently at baseline or IQCODE >4.5, measured using a patient's qualified surrogate, mental illness requiring long-term institutionalization, acquired or congenital mental retardation, Parkinson's disease, Huntington's disease, and/or coma or another severe deficit due to structural brain disease such as stroke, intracranial hemorrhage, cranial trauma, intracranial malignancy, anoxic brain injury, or cerebral edema.

4. History of torsades de pointes, documented baseline QT prolongation (congenital long QT syndrome), or QTc >500 ms at screening due to refractory electrolyte abnormalities, other drugs, or thyroid disease

5. Ongoing maintenance therapy with typical or atypical antipsychotics

6. History of neuroleptic malignant syndrome (NMS), haloperidol allergy, or ziprasidone allergy

7. Expected death within 24 hours of enrollment or lack of commitment to aggressive treatment by family or the medical team (e.g., likely withdrawal of life support measures within 24 hours of screening)

8. Inability to obtain informed consent from an authorized representative within 72 hours of meeting all inclusion criteria, i.e., developing qualifying organ dysfunction criteria.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Denver Health/University of Colorado Health Sciences Center	Denver	Colorado	United States	80204-4507
2	Yale University Medical Center	New Haven	Connecticut	United States	06520-8057
3	Indiana University	Indianapolis	Indiana	United States	46202-2915
4	University of Iowa	Iowa City	Iowa	United States	52242
5	University of Maryland Medical Center	Baltimore	Maryland	United States	21201
6	Massachusetts General Hospital	Boston	Massachusetts	United States	02114-2696
7	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
8	University of Michigan Health System	Ann Arbor	Michigan	United States	48109-5360
9	Albert Einstein Medical College-Montefiore Medical Center	Bronx	New York	United States	10461
10	University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7248
11	Moses Cone Health System	Greensboro	North Carolina	United States	27410
12	The Ohio State Medical Center	Columbus	Ohio	United States	43210-1228
13	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104-6205
14	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232-8300
15	Baylor Health Care System	Dallas	Texas	United States	75206
16	University of Washington	Seattle	Washington	United States	98195-9472

Sponsors and Collaborators

• Vanderbilt University Medical Center

Investigators

• Principal Investigator: E. Wesley Ely, MD, MPH, Vanderbilt University Medical Center

Study Documents (Full-Text)

• Study Protocol - Jun 22, 2016
• Statistical Analysis Plan - May 7, 2018

More Information

Publications

None provided.

• Responsible Party: Wes Ely, Professor of Medicine, Vanderbilt University Medical Center
• ClinicalTrials.gov Identifier: NCT01211522
• Other Study ID Numbers: AG035117-01A1; 101082
• First Posted: Sep 29, 2010
• Last Update Posted: Nov 18, 2019
• Last Verified: Oct 1, 2019

• Keywords provided by Wes Ely, Professor of Medicine, Vanderbilt University Medical Center: Delirium; Intensive care; Mechanical ventilation; Antipsychotic; Haloperidol; Ziprasidone; Randomized; Placebo; Sepsis; Sedation; Long-term cognitive impairment
• Additional relevant MeSH terms: Delirium; Cognitive Dysfunction; Haloperidol; Haloperidol decanoate; Ziprasidone

Study Results

Participant Flow

Arm/Group Title	Haloperidol	Ziprasidone	Placebo
Arm/Group Description	Haloperidol Haloperidol: Haloperidol, up to 10mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 5mg/mL. Patient will only receive IV while in the ICU.	Ziprasidone Ziprasidone: Ziprasidone, up to 20mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 10mg/mL. Patient will only receive IV while in the ICU.	Placebo Placebo: Placebo, up to 10mL q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes. Patient will only receive IV while in the ICU.
Period Title: Overall Study
STARTED	192	190	184
COMPLETED	189	183	179
NOT COMPLETED	3	7	5

Baseline Characteristics

Arm/Group Title	Haloperidol	Ziprasidone	Placebo	Total
Arm/Group Description	Haloperidol Haloperidol: Haloperidol, up to 10mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 5mg/mL. Patient will only receive IV while in the ICU.	Ziprasidone Ziprasidone: Ziprasidone, up to 20mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 10mg/mL. Patient will only receive IV while in the ICU.	Placebo Placebo: Placebo, up to 10mL q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes. Patient will only receive IV while in the ICU.	Total of all reporting groups
Overall Participants	192	190	184	566
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	61	61	59	60
Sex: Female, Male (Count of Participants)
Female	84 43.8%	82 43.2%	77 41.8%	243 42.9%
Male	108 56.3%	108 56.8%	107 58.2%	323 57.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	23 12%	27 14.2%	26 14.1%	76 13.4%
White	163 84.9%	151 79.5%	153 83.2%	467 82.5%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	6 3.1%	12 6.3%	5 2.7%	23 4.1%
Region of Enrollment (participants) [Number]
United States	192 100%	190 100%	184 100%	566 100%
Admission diagnosis (Count of Participants)
ARDS	44 22.9%	35 18.4%	39 21.2%	118 20.8%
Sepsis	43 22.4%	33 17.4%	35 19%	111 19.6%
Airway protection	46 24%	44 23.2%	53 28.8%	143 25.3%
COPD/asthma/other pulmonary	20 10.4%	28 14.7%	23 12.5%	71 12.5%
Surgery	13 6.8%	23 12.1%	13 7.1%	49 8.7%
CHF/MI/arrhythmia	6 3.1%	6 3.2%	6 3.3%	18 3.2%
Cirrhosis/liver failure	3 1.6%	3 1.6%	6 3.3%	12 2.1%
Seizures/neurologic disease	4 2.1%	1 0.5%	1 0.5%	6 1.1%
Other	13 6.8%	17 8.9%	8 4.3%	38 6.7%

Outcome Measures

1. Primary Outcome

Title	Delirium/Coma-free Days (DCFDs)
Description	Defined as the number of days during the 14-day intervention period (beginning on the day of randomization) that the patient was alive and experienced neither delirium nor coma.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Haloperidol	Ziprasidone	Placebo
Arm/Group Description	Haloperidol Haloperidol: Haloperidol, up to 10mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 5mg/mL. Patient will only receive IV while in the ICU.	Ziprasidone Ziprasidone: Ziprasidone, up to 20mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 10mg/mL. Patient will only receive IV while in the ICU.	Placebo Placebo: Placebo, up to 10mL q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes. Patient will only receive IV while in the ICU.
Measure Participants	192	190	184
Median (Inter-Quartile Range) [days]	8	8	7

2. Secondary Outcome

Title	Mortality
Description	Deaths within the specified timeframe
Time Frame	30-day and 90-day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Haloperidol	Ziprasidone	Placebo
Arm/Group Description	Haloperidol Haloperidol: Haloperidol, up to 10mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 5mg/mL. Patient will only receive IV while in the ICU.	Ziprasidone Ziprasidone: Ziprasidone, up to 20mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 10mg/mL. Patient will only receive IV while in the ICU.	Placebo Placebo: Placebo, up to 10mL q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes. Patient will only receive IV while in the ICU.
Measure Participants	192	190	184
30-day mortality	50 26%	53 27.9%	50 27.2%
90-day mortality	73 38%	65 34.2%	63 34.2%

3. Secondary Outcome

Title	Delirium Duration
Description	Duration of delirium during the intervention period
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Haloperidol	Ziprasidone	Placebo
Arm/Group Description	Haloperidol Haloperidol: Haloperidol, up to 10mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 5mg/mL. Patient will only receive IV while in the ICU.	Ziprasidone Ziprasidone: Ziprasidone, up to 20mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 10mg/mL. Patient will only receive IV while in the ICU.	Placebo Placebo: Placebo, up to 10mL q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes. Patient will only receive IV while in the ICU.
Measure Participants	192	190	184
Median (Inter-Quartile Range) [days]	4	4	4

4. Secondary Outcome

Title	Number of Participants With Torsades de Pointes
Time Frame	14 days plus 4-day post-study drug period (if longer than 14 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Haloperidol	Ziprasidone	Placebo
Arm/Group Description	Haloperidol Haloperidol: Haloperidol, up to 10mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 5mg/mL. Patient will only receive IV while in the ICU.	Ziprasidone Ziprasidone: Ziprasidone, up to 20mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 10mg/mL. Patient will only receive IV while in the ICU.	Placebo Placebo: Placebo, up to 10mL q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes. Patient will only receive IV while in the ICU.
Measure Participants	192	190	184
Count of Participants [Participants]	2 1%	0 0%	0 0%

5. Secondary Outcome

Title	Number of Participants With Extrapyramidal Symptoms
Time Frame	14 days plus 4-day post-study drug period (if longer than 14 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Haloperidol	Ziprasidone	Placebo
Arm/Group Description	Haloperidol Haloperidol: Haloperidol, up to 10mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 5mg/mL. Patient will only receive IV while in the ICU.	Ziprasidone Ziprasidone: Ziprasidone, up to 20mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 10mg/mL. Patient will only receive IV while in the ICU.	Placebo Placebo: Placebo, up to 10mL q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes. Patient will only receive IV while in the ICU.
Measure Participants	192	190	184
Count of Participants [Participants]	1 0.5%	1 0.5%	1 0.5%

6. Secondary Outcome

Title	Number of Participants With Neuroleptic Malignant Syndrome
Time Frame	14 days plus 4-day post-study drug period (if longer than 14 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Haloperidol	Ziprasidone	Placebo
Arm/Group Description	Haloperidol Haloperidol: Haloperidol, up to 10mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 5mg/mL. Patient will only receive IV while in the ICU.	Ziprasidone Ziprasidone: Ziprasidone, up to 20mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 10mg/mL. Patient will only receive IV while in the ICU.	Placebo Placebo: Placebo, up to 10mL q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes. Patient will only receive IV while in the ICU.
Measure Participants	192	190	184
Count of Participants [Participants]	0 0%	0 0%	0 0%

7. Secondary Outcome

Title	Time to Liberation From Mechanical Ventilation
Description	Days from randomization to successful liberation from mechanical ventilation, where "successful" indicates that liberation was followed by at least 48 hours alive and without reinitiation of invasive or noninvasive ventilation.
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Haloperidol	Ziprasidone	Placebo
Arm/Group Description	Haloperidol Haloperidol: Haloperidol, up to 10mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 5mg/mL. Patient will only receive IV while in the ICU.	Ziprasidone Ziprasidone: Ziprasidone, up to 20mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 10mg/mL. Patient will only receive IV while in the ICU.	Placebo Placebo: Placebo, up to 10mL q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes. Patient will only receive IV while in the ICU.
Measure Participants	192	190	184
Median (Inter-Quartile Range) [days]	2	3	3

8. Secondary Outcome

Title	Time to Final ICU Discharge
Description	Days from randomization to final, successful ICU discharge, where "successful" indicates that discharge was followed by at least 48 hours alive. "ICU discharge" is represented by readiness for ICU discharge indicated by a physician order for transfer to a lower level of care even if a bed availability problems prevent actual discharge from the ICU.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Haloperidol	Ziprasidone	Placebo
Arm/Group Description	Haloperidol Haloperidol: Haloperidol, up to 10mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 5mg/mL. Patient will only receive IV while in the ICU.	Ziprasidone Ziprasidone: Ziprasidone, up to 20mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 10mg/mL. Patient will only receive IV while in the ICU.	Placebo Placebo: Placebo, up to 10mL q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes. Patient will only receive IV while in the ICU.
Measure Participants	192	190	184
Median (Inter-Quartile Range) [days]	5	6	5

9. Secondary Outcome

Title	Time to ICU Readmission
Description	Days from first ICU discharge to next ICU readmission.
Time Frame	90 days after first ICU discharge

Outcome Measure Data

Analysis Population Description

Time to ICU readmission reported among those who were readmitted to the ICU

Arm/Group Title	Haloperidol	Ziprasidone	Placebo
Arm/Group Description	Haloperidol Haloperidol: Haloperidol, up to 10mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 5mg/mL. Patient will only receive IV while in the ICU.	Ziprasidone Ziprasidone: Ziprasidone, up to 20mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 10mg/mL. Patient will only receive IV while in the ICU.	Placebo Placebo: Placebo, up to 10mL q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes. Patient will only receive IV while in the ICU.
Measure Participants	27	18	23
Median (Inter-Quartile Range) [days]	5	5	4

10. Secondary Outcome

Title	Time to Hospital Discharge
Description	Days from randomization to successful hospital discharge, where "successful" indicates that discharge was followed by at least 48 hours alive.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Haloperidol	Ziprasidone	Placebo
Arm/Group Description	Haloperidol Haloperidol: Haloperidol, up to 10mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 5mg/mL. Patient will only receive IV while in the ICU.	Ziprasidone Ziprasidone: Ziprasidone, up to 20mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 10mg/mL. Patient will only receive IV while in the ICU.	Placebo Placebo: Placebo, up to 10mL q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes. Patient will only receive IV while in the ICU.
Measure Participants	192	190	184
Median (Inter-Quartile Range) [days]	13	12	13

Adverse Events

Time Frame	During the period when the patients were receiving a trial drug or placebo and for 4 days after discontinuation, we assessed the patients for side effects. We also collected clinical outcomes data until hospital discharge or up to 90 days.
Arm/Group Title	Haloperidol		Ziprasidone		Placebo
Arm/Group Description	Haloperidol Haloperidol: Haloperidol, up to 10mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 5mg/mL. Patient will only receive IV while in the ICU.		Ziprasidone Ziprasidone: Ziprasidone, up to 20mg q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes at concentrations of 10mg/mL. Patient will only receive IV while in the ICU.		Placebo Placebo: Placebo, up to 10mL q12 hours, will be administered intravenously (IV) by bolus over up to 5 minutes. Patient will only receive IV while in the ICU.
All Cause Mortality
	Haloperidol		Ziprasidone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	73/192 (38%)		65/190 (34.2%)		63/184 (34.2%)
Serious Adverse Events
	Haloperidol		Ziprasidone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/192 (1.6%)		1/190 (0.5%)		1/184 (0.5%)
Cardiac disorders
Torsades de pointes	2/192 (1%)		1/190 (0.5%)		1/184 (0.5%)
Nervous system disorders
Neuroleptic malignant syndrome	0/192 (0%)		0/190 (0%)		0/184 (0%)
Extrapyramidal symptoms	1/192 (0.5%)		1/190 (0.5%)		1/184 (0.5%)
Other (Not Including Serious) Adverse Events
	Haloperidol		Ziprasidone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	55/192 (28.6%)		70/190 (36.8%)		56/184 (30.4%)
Cardiac disorders
Prolonged QTc	13/192 (6.8%)		20/190 (10.5%)		10/184 (5.4%)
Nervous system disorders
Oversedation	42/192 (21.9%)		50/190 (26.3%)		46/184 (25%)

Limitations/Caveats

[Not Specified]

More Information

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.