The Modifying the Impact of ICU-Associated Neurological Dysfunction-USA (MIND-USA) Study
This study is currently recruiting participants.
Verified February 2013 by Vanderbilt University
Sponsor:
Vanderbilt University
Information provided by (Responsible Party):
Wes Ely, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01211522
First received: September 28, 2010
Last updated: February 5, 2013
Last verified: February 2013
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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 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.
| Condition | Intervention | Phase |
|---|---|---|
|
Delirium Impaired Cognition Long Term Psychologic Disorders |
Drug: Haloperidol Drug: Ziprasidone Drug: Placebo |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | The MIND-USA Study: Modifying the Impact of ICU-Associated Neurological Dysfunction |
Resource links provided by NLM:
Drug Information available for:
Haloperidol
Haloperidol decanoate
Ziprasidone hydrochloride
Ziprasidone
Ziprasidone mesylate
U.S. FDA Resources
Further study details as provided by Vanderbilt University:
Primary Outcome Measures:
- Delirium/coma-free days [ Time Frame: 14 days ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Survival [ Time Frame: 30-day, 90-day, and 1-year ] [ Designated as safety issue: No ]
- Delirium duration [ Time Frame: 14 days ] [ Designated as safety issue: No ]
- ICU length of stay [ Time Frame: 1 to 90 days ] [ Designated as safety issue: No ]Time to ICU discharge, 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.
- Hospital length of stay [ Time Frame: 1 to 90 days ] [ Designated as safety issue: No ]
- Ventilator-free days [ Time Frame: 14 days ] [ Designated as safety issue: No ]
- ICU readmission [ Time Frame: 1 to 90 days ] [ Designated as safety issue: No ]
- Hospital readmission [ Time Frame: 1 to 365 days ] [ Designated as safety issue: No ]
- Neuropsychological dysfunction [ Time Frame: 3-month, 12-month ] [ Designated as safety issue: No ]Assessed using a battery of cognitive tests.
- Quality of life [ Time Frame: 3-month, 12-month ] [ Designated as safety issue: No ]
- Posttraumatic stress disorder [ Time Frame: 3-month, 12-month ] [ Designated as safety issue: No ]
- QTc prolongation [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
- Extrapyramidal symptoms [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
- Neuroleptic malignant syndrome [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 876 |
| Study Start Date: | December 2011 |
| Estimated Study Completion Date: | February 2016 |
| Estimated Primary Completion Date: | July 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: 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 Name: Haldol
|
| Experimental: 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 Name: Geodon
|
| Placebo Comparator: 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.
Other Name: Placebo
|
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).
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- adult patients (≥18 years old)
- in a medical and/or surgical ICU
- on mechanical ventilation or non-invasive positive pressure ventilation (NIPPV), and/or requiring vasopressors due to shock
- delirious (according to the CAM-ICU)
Exclusion Criteria:
- 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
- Pregnancy or breastfeeding (negative pregnancy test required prior to enrollment of female patients of childbearing age)
- 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.
- 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
- Ongoing maintenance therapy with typical or atypical antipsychotics
- History of neuroleptic malignant syndrome (NMS), haloperidol allergy, or ziprasidone allergy
- 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)
- 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01211522
Contacts
| Contact: E. Wesley Ely, MD, MPH | 615-936-3395 | wes.ely@vanderbilt.edu |
| Contact: Timothy D Girard, MD, MSCI | 615-936-1010 | timothy.girard@vanderbilt.edu |
Locations
| United States, Colorado | |
| Denver Health/University of Colorado Health Sciences Center | Recruiting |
| Denver, Colorado, United States, 80204-4507 | |
| Contact: Ivor S Douglas, MD 303-436-5905 idouglas@dhha.org | |
| Principal Investigator: Ivor S Douglas, MD | |
| United States, Connecticut | |
| Yale University Medical Center | Recruiting |
| New Haven, Connecticut, United States, 06520-8057 | |
| Contact: Margaret A Pisani, MD 203-785-3627 margaret.pisani@yale.edu | |
| Principal Investigator: Margaret A Pisani, MD | |
| United States, Indiana | |
| Indiana University | Active, not recruiting |
| Indianapolis, Indiana, United States, 46202-2915 | |
| United States, Iowa | |
| University of Iowa | Recruiting |
| Iowa City, Iowa, United States, 52242 | |
| Contact: Gregory A Schmidt, MD 319-356-4187 gregory-a-schmidt@uiowa.edu | |
| Principal Investigator: Gregory A Schmidt, MD | |
| United States, Maryland | |
| University of Maryland Medical Center | Recruiting |
| Baltimore, Maryland, United States, 21201 | |
| Contact: Peter Rock, MD, MBA 410-328-8919 prock@anes.umm.edu | |
| Principal Investigator: Peter Rock, MD, MBA | |
| United States, Massachusetts | |
| Brigham and Women's Hospital | Recruiting |
| Boston, Massachusetts, United States, 02115 | |
| Contact: Atul Malhotra, MD 617-732-4013 amalhotral@partners.org | |
| Principal Investigator: Atul Malhotra, MD | |
| Massachusetts General Hospital | Recruiting |
| Boston, Massachusetts, United States, 02114-2696 | |
| Contact: Ulrich Schmidt, MD, PhD 617-724-6490 uschmidt@partners.org | |
| Principal Investigator: Ulrich Schmidt, MD, PhD | |
| United States, Michigan | |
| University of Michigan Health System | Recruiting |
| Ann Arbor, Michigan, United States, 48109-5360 | |
| Contact: Robert C Hyzy, MD 734-936-5201 rhyzy@med.umich.edu | |
| Principal Investigator: Robert C Hyzy, MD | |
| United States, New York | |
| Albert Einstein Medical College-Montefiore Medical Center | Recruiting |
| Bronx, New York, United States, 10461 | |
| Contact: Michelle Ng Gong, MD, MS 718-430-3712 mgong@montefiore.org | |
| Principal Investigator: Michelle Ng Gong, MD, MS | |
| United States, North Carolina | |
| University of North Carolina - Chapel Hill | Recruiting |
| Chapel Hill, North Carolina, United States, 27599-7248 | |
| Contact: Shannon S Carson, MD 919-966-2531 shannon_carson@med.unc.edu | |
| Principal Investigator: Shannon S Carson, MD | |
| Moses Cone Health System | Recruiting |
| Greensboro, North Carolina, United States, 27410 | |
| Contact: Daniel J Feinstein, MD 336-832-2432 daniel.feinstein@mosescone.com | |
| Principal Investigator: Daniel J Feinstein, MD | |
| Wake Forest University | Recruiting |
| Winston-Salem, North Carolina, United States, 27157 | |
| Contact: Robert D Hite, MD 336-716-8898 dhite@wfubmc.edu | |
| Principal Investigator: Robert D Hite, MD | |
| United States, Ohio | |
| The Ohio State Medical Center | Recruiting |
| Columbus, Ohio, United States, 43210-1228 | |
| Contact: Matthew C. Exline, MD, MPH 614-293-4925 matthew.exline@osumc.edu | |
| Principal Investigator: Matthew C. Exline, MD, MPH | |
| United States, Pennsylvania | |
| University of Pennsylvania | Recruiting |
| Philadelphia, Pennsylvania, United States, 19104-6205 | |
| Contact: William Schweickert, MD 215-898-7293 William.Schweickert@uphs.upenn.edu | |
| Principal Investigator: William Schweickert, MD | |
| United States, Tennessee | |
| Vanderbilt University Medical Center | Recruiting |
| Nashville, Tennessee, United States, 37232-8300 | |
| Contact: Wes E. Ely, MD, MPH 615-936-3702 wes.ely@vanderbilt.edu | |
| Contact: Tim Girard, MD, MPH 1-615-936-3702 timothy.girard@vanderbilt.edu | |
| United States, Texas | |
| Baylor Health Care System | Recruiting |
| Dallas, Texas, United States, 75206 | |
| Contact: Andrew L Masica, MD 214-265-3670 AndrewMa@BaylorHealth.edu | |
| Principal Investigator: Andrew L Masica, MD | |
Sponsors and Collaborators
Vanderbilt University
Investigators
| Principal Investigator: | E. Wesley Ely, MD, MPH | Vanderbilt University |
More Information
No publications provided
| Responsible Party: | Wes Ely, Professor of Medicine, Vanderbilt University |
| ClinicalTrials.gov Identifier: | NCT01211522 History of Changes |
| Other Study ID Numbers: | AG035117-01A1, 101082 |
| Study First Received: | September 28, 2010 |
| Last Updated: | February 5, 2013 |
| Health Authority: | United States: Food and Drug Administration United States: Institutional Review Board |
Keywords provided by Vanderbilt University:
|
Delirium Intensive care Mechanical ventilation Antipsychotic Haloperidol Ziprasidone |
Randomized Placebo Sepsis Sedation Long-term cognitive impairment |
Additional relevant MeSH terms:
|
Delirium Cognition Disorders Confusion Neurobehavioral Manifestations Neurologic Manifestations Nervous System Diseases Signs and Symptoms Delirium, Dementia, Amnestic, Cognitive Disorders Mental Disorders Haloperidol Haloperidol decanoate Ziprasidone Antiemetics Autonomic Agents Peripheral Nervous System Agents |
Physiological Effects of Drugs Pharmacologic Actions Central Nervous System Agents Therapeutic Uses Gastrointestinal Agents Antipsychotic Agents Tranquilizing Agents Central Nervous System Depressants Psychotropic Drugs Dopamine Antagonists Dopamine Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Anti-Dyskinesia Agents Serotonin Antagonists |
ClinicalTrials.gov processed this record on May 23, 2013