The Modifying the Impact of ICU-Associated Neurological Dysfunction-USA (MIND-USA) Study
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Cognitive Studies, Hospital, Neurology, Psychiatric |
| Therapuetic Areas: | Neurology, Psychiatry / Psychology, Other |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 9/14/2018 |
| Start Date: | December 2011 |
| End Date: | July 15, 2025 |
MIND-USA Study: Modifying the Impact of ICU-Associated Neurological Dysfunction
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.
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.
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.
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.
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.
We found this trial at
16
sites
1500 E Medical Center Dr
Ann Arbor, Michigan 48109
Ann Arbor, Michigan 48109
(734) 936-4000
Principal Investigator: Robert C Hyzy, MD
Phone: 734-936-5201
University of Michigan Health System The University of Michigan is home to one of the...
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75 Francis street
Boston, Massachusetts 02115
Boston, Massachusetts 02115
(617) 732-5500
Principal Investigator: Robert L Owens, MD
Phone: 617-983-7489
Brigham and Women's Hosp Boston’s Brigham and Women’s Hospital (BWH) is an international leader in...
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Chapel Hill, North Carolina 27599
(919) 962-2211
Principal Investigator: Shannon S Carson, MD
Phone: 919-966-2531
University of North Carolina at Chapel Hill Carolina’s vibrant people and programs attest to the...
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Indiana University INDIANA UNIVERSITY is a major multi-campus public research institution, grounded in the liberal...
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University of Iowa With just over 30,000 students, the University of Iowa is one of...
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1211 Medical Center Dr
Nashville, Tennessee 37232
Nashville, Tennessee 37232
(615) 322-5000
Phone: 615-936-3702
Vanderbilt Univ Med Ctr Vanderbilt University Medical Center (VUMC) is a comprehensive healthcare facility dedicated...
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Seattle, Washington 98104
(206) 543-2100
Principal Investigator: Catherine Hough, MD
Phone: 206-744-3356
Univ of Washington Founded in 1861 by a private gift of 10 acres in what...
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22 S Greene St
Baltimore, Maryland 21201
Baltimore, Maryland 21201
(410) 328-8667
Principal Investigator: Peter Rock, MD, MBA
Phone: 410-328-8919
University of Maryland Medical Center Founded in 1823 as the Baltimore Infirmary, the University of...
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Bronx, New York 10461
Principal Investigator: Michelle Ng Gong, MD, MS
Phone: 718-430-3712
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Columbus, Ohio 43210
Principal Investigator: Matthew C. Exline, MD, MPH
Phone: 614-293-4925
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Denver, Colorado 80204
Principal Investigator: Ivor S Douglas, MD
Phone: 303-436-5905
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Greensboro, North Carolina
Principal Investigator: Daniel J Feinstein, MD
Phone: 336-832-2432
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New Haven, Connecticut 06520
Principal Investigator: Margaret A Pisani, MD
Phone: 203-785-3627
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Univ of Pennsylvania Penn has a long and proud tradition of intellectual rigor and pursuit...
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