Trial record 1 of 1 for:    MIND-USA
Previous Study | Return to List | Next Study

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:
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
  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:


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:

  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
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 April 17, 2014