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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01211522
Recruitment Status : Completed
First Posted : September 29, 2010
Results First Posted : August 20, 2019
Last Update Posted : September 10, 2019
Sponsor:
Information provided by (Responsible Party):
Wes Ely, Vanderbilt University Medical Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Delirium
Impaired Cognition
Long Term Psychologic Disorders
Interventions Drug: Haloperidol
Drug: Ziprasidone
Drug: Placebo
Enrollment 566
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Haloperidol Ziprasidone Placebo
Hide 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
Reason Not Completed
Withdrawal by Subject             3             7             5
Arm/Group Title Haloperidol Ziprasidone Placebo Total
Hide 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 Number of Baseline Participants 192 190 184 566
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 192 participants 190 participants 184 participants 566 participants
61
(51 to 69)
61
(50 to 69)
59
(52 to 67)
60
(51 to 68)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 192 participants 190 participants 184 participants 566 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)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 192 participants 190 participants 184 participants 566 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
23
  12.0%
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
   0.0%
0
   0.0%
Unknown or Not Reported
6
   3.1%
12
   6.3%
5
   2.7%
23
   4.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 192 participants 190 participants 184 participants 566 participants
192 190 184 566
Admission diagnosis  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 192 participants 190 participants 184 participants 566 participants
ARDS
44
  22.9%
35
  18.4%
39
  21.2%
118
  20.8%
Sepsis
43
  22.4%
33
  17.4%
35
  19.0%
111
  19.6%
Airway protection
46
  24.0%
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%
1.Primary Outcome
Title Delirium/Coma-free Days (DCFDs)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Haloperidol Ziprasidone Placebo
Hide 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.

Overall Number of Participants Analyzed 192 190 184
Median (Inter-Quartile Range)
Unit of Measure: days
8
(0 to 11)
8
(2 to 11)
7
(0 to 11)
2.Secondary Outcome
Title Mortality
Hide Description Deaths within the specified timeframe
Time Frame 30-day and 90-day
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Haloperidol Ziprasidone Placebo
Hide 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.

Overall Number of Participants Analyzed 192 190 184
Measure Type: Count of Participants
Unit of Measure: Participants
30-day mortality
50
  26.0%
53
  27.9%
50
  27.2%
90-day mortality
73
  38.0%
65
  34.2%
63
  34.2%
3.Secondary Outcome
Title Delirium Duration
Hide Description Duration of delirium during the intervention period
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Haloperidol Ziprasidone Placebo
Hide 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.

Overall Number of Participants Analyzed 192 190 184
Median (Inter-Quartile Range)
Unit of Measure: days
4
(2 to 7)
4
(2 to 6)
4
(2 to 8)
4.Secondary Outcome
Title Number of Participants With Torsades de Pointes
Hide Description [Not Specified]
Time Frame 14 days plus 4-day post-study drug period (if longer than 14 days)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Haloperidol Ziprasidone Placebo
Hide 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.

Overall Number of Participants Analyzed 192 190 184
Measure Type: Count of Participants
Unit of Measure: Participants
2
   1.0%
0
   0.0%
0
   0.0%
5.Secondary Outcome
Title Number of Participants With Extrapyramidal Symptoms
Hide Description [Not Specified]
Time Frame 14 days plus 4-day post-study drug period (if longer than 14 days)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Haloperidol Ziprasidone Placebo
Hide 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.

Overall Number of Participants Analyzed 192 190 184
Measure Type: Count of Participants
Unit of Measure: Participants
1
   0.5%
1
   0.5%
1
   0.5%
6.Secondary Outcome
Title Number of Participants With Neuroleptic Malignant Syndrome
Hide Description [Not Specified]
Time Frame 14 days plus 4-day post-study drug period (if longer than 14 days)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Haloperidol Ziprasidone Placebo
Hide 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.

Overall Number of Participants Analyzed 192 190 184
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
7.Secondary Outcome
Title Time to Liberation From Mechanical Ventilation
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Haloperidol Ziprasidone Placebo
Hide 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.

Overall Number of Participants Analyzed 192 190 184
Median (Inter-Quartile Range)
Unit of Measure: days
2
(1 to 6)
3
(2 to 5)
3
(1 to 5)
8.Secondary Outcome
Title Time to Final ICU Discharge
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Haloperidol Ziprasidone Placebo
Hide 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.

Overall Number of Participants Analyzed 192 190 184
Median (Inter-Quartile Range)
Unit of Measure: days
5
(3 to 13)
6
(3 to 10)
5
(3 to 14)
9.Secondary Outcome
Title Time to ICU Readmission
Hide Description Days from first ICU discharge to next ICU readmission.
Time Frame 90 days after first ICU discharge
Hide Outcome Measure Data
Hide Analysis Population Description
Time to ICU readmission reported among those who were readmitted to the ICU
Arm/Group Title Haloperidol Ziprasidone Placebo
Hide 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.

Overall Number of Participants Analyzed 27 18 23
Median (Inter-Quartile Range)
Unit of Measure: days
5
(2 to 9)
5
(2 to 9)
4
(1 to 8)
10.Secondary Outcome
Title Time to Hospital Discharge
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Haloperidol Ziprasidone Placebo
Hide 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.

Overall Number of Participants Analyzed 192 190 184
Median (Inter-Quartile Range)
Unit of Measure: days
13
(8 to 22)
12
(8 to 21)
13
(8 to 23)
11.Secondary Outcome
Title Hospital Readmission
Hide Description Readmission to the hospital after index hospital discharge determined by self-report during follow-up interviews.
Time Frame 365 days
Outcome Measure Data Not Reported
12.Secondary Outcome
Title Neuropsychological Dysfunction
Hide Description Assessed using Telephone Interview for Cognitive Status (TICS), Digit Span and Similarities from the WAIS-III, Confusion Assessment Method (CAM) Telephone version, Paragraph Recall (both immediate and delayed portions) from the WMS-III, Controlled Oral Word Association Test (COWA), and the Hayling Test. These assessments will be scored in standard fashion and will allow us to characterize cognitive impairment across patients.
Time Frame 3 and 12 months post-randomization
Outcome Measure Data Not Reported
13.Secondary Outcome
Title EQ-5D-3L Scores
Hide Description [Not Specified]
Time Frame 3 and 12 months post-randomization
Outcome Measure Data Not Reported
14.Secondary Outcome
Title Katz Activities of Daily Living Score
Hide Description [Not Specified]
Time Frame 3 and 12 months post-randomization
Outcome Measure Data Not Reported
15.Secondary Outcome
Title Functional Activities Questionnaire Score
Hide Description [Not Specified]
Time Frame 3 and 12 months post-randomization
Outcome Measure Data Not Reported
16.Secondary Outcome
Title Posttraumatic Stress Disorder
Hide Description Assessed using the PTSD Checklist (PCL-S, event specific version) with respondents instructed to answer questions in reference to the ICU experience.
Time Frame 3 and 12 months post-randomization
Outcome Measure Data Not Reported
17.Secondary Outcome
Title Healthcare Utilization
Hide Description Assessed using the Healthcare Utilization Survey
Time Frame 3 and 12 months post-randomization
Outcome Measure Data Not Reported
18.Secondary Outcome
Title Employment
Hide Description Return to work (if previously employed)
Time Frame 3 and 12 months post-randomization
Outcome Measure Data Not Reported
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.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Haloperidol Ziprasidone Placebo
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%)
Total   73/192 (38.02%)   65/190 (34.21%)   63/184 (34.24%) 
Show Serious Adverse Events Hide Serious Adverse Events
Haloperidol Ziprasidone Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/192 (1.56%)   1/190 (0.53%)   1/184 (0.54%) 
Cardiac disorders       
Torsades de pointes   2/192 (1.04%)  1/190 (0.53%)  1/184 (0.54%) 
Nervous system disorders       
Neuroleptic malignant syndrome   0/192 (0.00%)  0/190 (0.00%)  0/184 (0.00%) 
Extrapyramidal symptoms   1/192 (0.52%)  1/190 (0.53%)  1/184 (0.54%) 
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Haloperidol Ziprasidone Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   55/192 (28.65%)   70/190 (36.84%)   56/184 (30.43%) 
Cardiac disorders       
Prolonged QTc   13/192 (6.77%)  20/190 (10.53%)  10/184 (5.43%) 
Nervous system disorders       
Oversedation   42/192 (21.88%)  50/190 (26.32%)  46/184 (25.00%) 
Indicates events were collected by systematic assessment
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
Layout table for Results Point of Contact information
Name/Title: E Wesley Ely
Organization: Vanderbilt University Medical Center
Phone: ‭(615) 936-3395‬
EMail: wes.ely@vumc.org
Layout table for additonal information
Responsible Party: Wes Ely, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT01211522     History of Changes
Other Study ID Numbers: AG035117-01A1
101082 ( Other Identifier: Vanderbilt University Institutional Review Board )
First Submitted: September 28, 2010
First Posted: September 29, 2010
Results First Submitted: July 16, 2019
Results First Posted: August 20, 2019
Last Update Posted: September 10, 2019