The Modifying the Impact of ICU-Associated Neurological Dysfunction-USA (MIND-USA) Study
Description
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 antipsychoticsâ¿¿haloperidol and ziprasidone, in this caseâ¿¿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 876 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), 292 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.
Study Start Date
December 2011
Estimated Completion Date
July 2019
Interventions
- Drug: Haloperidol
- Drug: Ziprasidone
- Drug: Placebo
Specialties
- Internal Medicine: Neurology
- Neurology: Dementia
- Emergency Medicine: Neurology/Neurosurgery
MeSH Terms
- Cognition Disorders
- Delirium
- Haloperidol
- Sepsis
- Ziprasidone
Study ID
Vanderbilt University -- AG035117-01A1
Status
Unknown
Trial ID
Study Type
Interventional
Trial Phase
Phase 3
Enrollment Quota
561
Sponsor
Vanderbilt University
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.
Gender
Both
Ages
18 Years and older
Accepts Healthy Volunteers
No
Study Locations and Contact Information (7)
Study Location | Distance | Name | Phone | |
---|---|---|---|---|
Brigham and Womens Hospital - Boston, Massachusetts | 2.6 miles | Robert L Owens MD | 617-983-7489 | rowens@partners.org |
Albert Einstein Medical CollegeMontefiore Medical Center - Bronx, New York | 176.6 miles | Michelle Ng Gong MD MS | 718-430-3712 | mgong@montefiore.org |
University of Maryland Medical Center - Baltimore, Maryland | 358.9 miles | Peter Rock MD MBA | 410-328-8919 | prock@anes.umm.edu |
Moses Cone Health System - Greensboro, North Carolina | 639.9 miles | Daniel J Feinstein MD | 336-832-2432 | daniel.feinstein@mosescone.com |
Wake Forest University - Winston-Salem, North Carolina | 659.2 miles | None | None | None |
University of Iowa - Iowa City, Iowa | 1,050.4 miles | None | None | None |
Baylor Health Care System - Dallas, Texas | 1,547.9 miles | None | None | None |