The MIND Study: Modifying the INcidence of Delirium

NCT00096863 | Completed Phase 2 DMC

• 1 other identifier: IRB # 040542
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 5

Brief Summary

Delirium is associated with increased risk of death, prolonged stay, higher cost of care, and likely long-term brain deficits in survivors. This form of brain dysfunction occurs in intensive care unit (ICU) patients in epidemic proportions, and the scope of this problem is likely to worsen in upcoming years due to the aging of our population and increased utilization of the ICU. Currently, delirium goes unrecognized and untreated in the vast majority of circumstances in the ICU unless the patient presents with hyperactive delirium and agitation. In the latter circumstance, a commonly used typical antipsychotic called haloperidol is considered the principal agent for treating delirium based largely on anecdotal evidence to support its usefulness, though no placebo controlled trials exist. There are no FDA approved medications for delirium. The atypical antipsychotics provide a promising alternative for the treatment of delirium due to their enhanced beneficial effects on positive (agitated) and negative (quiet) symptoms proven in mania and schizophrenia, reduced risk for side effects common to haloperidol such as extrapyramidal symptomatology, and less potentially lethal heart rhythm disturbances. It is imperative that well-designed phase II studies to determine proof of principle be conducted. A pilot study of feasibility to begin assessing the role of antipsychotics in the management of ICU delirium.

Conditions

Delirium; Cognition Disorders

Keywords

Delirium; Cognition Disorders; Antipsychotics; Mechanical Ventilation; Critical Illness

Outcome Measures

Primary Outcomes (1)

• Days alive and free of delirium and coma (delirium and coma free days)

  enrollment to day 21

Secondary Outcomes (8)

• Severity of neuropsychological dysfunction at hospital discharge

  48-72 following d/c of study drug

• alive and free of delirium (delirium free days)

  enrollment to day 21

• Length of stay on mechanical ventilation

  enrollment to day 21

• Mechanical ventilation free days

  enrollment to day 21

• length of stay in the ICU

  enrollment to day 21

Study Arms (3)

A - placebo

PLACEBO COMPARATOR

per oral pill

Other: Placebo

B

ACTIVE COMPARATOR

Ziprasidone

Drug: Ziprasidone

C

ACTIVE COMPARATOR

Haloperidol

Drug: Haloperidol

Interventions

Ziprasidone DRUG

B

Haloperidol DRUG

C

Placebo OTHER

Also known as: per oral pill

A - placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Medical or surgical ICU patients on mechanical ventilation who are receiving sedatives or analgesics or displaying an abnormal level of consciousness (delirium or coma).

You may not qualify if:

• Subjects expected to have a short time on mechanical ventilation. That is, those in whom the likelihood for the need for mechanical ventilation is less than 24 hours.
• Subjects who have been on mechanical ventilation for more than 72 hours.
• Subjects in whom gastric access is not available (i.e., no enteral feeding tube or NG/OG tube)and is not anticipated to be available for 48 hours.
• Subjects younger than 18 years old.
• Subjects who are pregnant (a pregnancy test will be performed on all women of child bearing age) or breastfeeding.
• Inability to obtain informed consent from the subject or the subject's authorized representative.
• Documented history of allergic reaction to ziprasidone or haloperidol.
• Subjects admitted to the ICU for drug/alcohol overdose, suicide attempts, alcohol withdrawal/delirium tremens.
• Subjects with active seizures or cerebrovascular accident within the last 2 weeks.
• Subjects who are benzodiazepine dependent at the time of index hospitalization (i.e., patients on benzodiazepines as outpatient and whose attending judges it unsafe to withhold these medications due to risk for withdrawal syndrome).
• Subjects with chronic pain syndromes or who are on maintenance narcotics.
• Subjects with a history of torsades de pointes, known history of QT prolongation (e.g., congenital long QT syndrome), a QTc at baseline of 500 ms or over in the absence of bundle branch block, documented myocardial infarction within the previous 2 weeks, or uncompensated NYHA IV heart failure (dyspnea or anginal syndrome present at rest due to CHF). \[NOTE: ICU patients who have an incidental rise in troponin in the absence of definitive ischemic ECG changes remain eligible\]
• Subjects who are on neuroleptic therapy as an outpatient maintenance drug (e.g., haloperidol, mesoridazine, thorazine, chlorpromazine, trifluoperazine, droperidol, risperidone, quetiapine, olanzapine, or ziprasidone).
• Subjects who are receiving and will continue to receive other drugs that prolong the QT interval such as sotalol, quinidine, other Class Ia or III anti-arrhythmics, dofetilide (Tikosyn for arrhythmias), pimozide (for Tourette's), gatifloxacin, moxifloxacin (levofloxacin permissible), pentamidine, tacrolimus (Prograf), dolasetron (Anzemet). Azithromycin is an acceptable medication for study patients, and anyone slated to receive (or receiving) either clarithromycin or erythromycin can be switched to azithromycin by their primary team and be enrolled into the study the following day. Patients receiving clindamycin or clotrimazole will be excluded from the study.
• Subjects who have a history of neuroleptic malignant syndrome.

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (5)

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Moses Cone

Greensboro, North Carolina, 27401, United States

Location

Saint Thomas Hospital

Nashville, Tennessee, 37205, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (20)

• Ely EW, Margolin R, Francis J, May L, Truman B, Dittus R, Speroff T, Gautam S, Bernard GR, Inouye SK. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med. 2001 Jul;29(7):1370-9. doi: 10.1097/00003246-200107000-00012.

  PMID: 11445689 BACKGROUND

• Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, Truman B, Speroff T, Gautam S, Margolin R, Hart RP, Dittus R. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA. 2001 Dec 5;286(21):2703-10. doi: 10.1001/jama.286.21.2703.

  PMID: 11730446 BACKGROUND

• Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr, Inouye SK, Bernard GR, Dittus RS. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004 Apr 14;291(14):1753-62. doi: 10.1001/jama.291.14.1753.

  PMID: 15082703 BACKGROUND

• Ely EW, Gautam S, Margolin R, Francis J, May L, Speroff T, Truman B, Dittus R, Bernard R, Inouye SK. The impact of delirium in the intensive care unit on hospital length of stay. Intensive Care Med. 2001 Dec;27(12):1892-900. doi: 10.1007/s00134-001-1132-2. Epub 2001 Nov 8.

  PMID: 11797025 BACKGROUND

• Jackson JC, Hart RP, Gordon SM, Shintani A, Truman B, May L, Ely EW. Six-month neuropsychological outcome of medical intensive care unit patients. Crit Care Med. 2003 Apr;31(4):1226-34. doi: 10.1097/01.CCM.0000059996.30263.94.

  PMID: 12682497 BACKGROUND

• Milbrandt EB, Deppen S, Harrison PL, Shintani AK, Speroff T, Stiles RA, Truman B, Bernard GR, Dittus RS, Ely EW. Costs associated with delirium in mechanically ventilated patients. Crit Care Med. 2004 Apr;32(4):955-62. doi: 10.1097/01.ccm.0000119429.16055.92.

  PMID: 15071384 BACKGROUND

• Jackson JC, Gordon SM, Hart RP, Hopkins RO, Ely EW. The association between delirium and cognitive decline: a review of the empirical literature. Neuropsychol Rev. 2004 Jun;14(2):87-98. doi: 10.1023/b:nerv.0000028080.39602.17.

  PMID: 15264710 BACKGROUND

• Jacobi J, Fraser GL, Coursin DB, Riker RR, Fontaine D, Wittbrodt ET, Chalfin DB, Masica MF, Bjerke HS, Coplin WM, Crippen DW, Fuchs BD, Kelleher RM, Marik PE, Nasraway SA Jr, Murray MJ, Peruzzi WT, Lumb PD; Task Force of the American College of Critical Care Medicine (ACCM) of the Society of Critical Care Medicine (SCCM), American Society of Health-System Pharmacists (ASHP), American College of Chest Physicians. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med. 2002 Jan;30(1):119-41. doi: 10.1097/00003246-200201000-00020. No abstract available.

  PMID: 11902253 BACKGROUND

• Ely EW, Stephens RK, Jackson JC, Thomason JW, Truman B, Gordon S, Dittus RS, Bernard GR. Current opinions regarding the importance, diagnosis, and management of delirium in the intensive care unit: a survey of 912 healthcare professionals. Crit Care Med. 2004 Jan;32(1):106-12. doi: 10.1097/01.CCM.0000098033.94737.84.

  PMID: 14707567 BACKGROUND

• Frankenburg FR. Pharmacological treatment of delirium in the intensive care unit. JAMA. 2004 Jul 14;292(2):168; author reply 168-9. doi: 10.1001/jama.292.2.168-a. No abstract available.

  PMID: 15249562 BACKGROUND

• Kapur S, Seeman P. Antipsychotic agents differ in how fast they come off the dopamine D2 receptors. Implications for atypical antipsychotic action. J Psychiatry Neurosci. 2000 Mar;25(2):161-6.

  PMID: 10740989 BACKGROUND

• Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med. 2004 Mar 4;350(10):1013-22. doi: 10.1056/NEJMra032426. No abstract available.

  PMID: 14999113 BACKGROUND

• Schmidt AW, Lebel LA, Howard HR Jr, Zorn SH. Ziprasidone: a novel antipsychotic agent with a unique human receptor binding profile. Eur J Pharmacol. 2001 Aug 17;425(3):197-201. doi: 10.1016/s0014-2999(01)01188-8.

  PMID: 11513838 BACKGROUND

• Seneff MG, Mathews RA. Use of haloperidol infusions to control delirium in critically ill adults. Ann Pharmacother. 1995 Jul-Aug;29(7-8):690-3. doi: 10.1177/106002809502907-806.

  PMID: 8520081 BACKGROUND

• Leso L, Schwartz TL. Ziprasidone treatment of delirium. Psychosomatics. 2002 Jan-Feb;43(1):61-2. doi: 10.1176/appi.psy.43.1.61. No abstract available.

  PMID: 11927760 BACKGROUND

• Brook S, Lucey JV, Gunn KP. Intramuscular ziprasidone compared with intramuscular haloperidol in the treatment of acute psychosis. Ziprasidone I.M. Study Group. J Clin Psychiatry. 2000 Dec;61(12):933-41. doi: 10.4088/jcp.v61n1208.

  PMID: 11206599 BACKGROUND

• Ely EW, Truman B, Shintani A, Thomason JW, Wheeler AP, Gordon S, Francis J, Speroff T, Gautam S, Margolin R, Sessler CN, Dittus RS, Bernard GR. Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS). JAMA. 2003 Jun 11;289(22):2983-91. doi: 10.1001/jama.289.22.2983.

  PMID: 12799407 BACKGROUND

• Simpson GM, Angus JW. A rating scale for extrapyramidal side effects. Acta Psychiatr Scand Suppl. 1970;212:11-9. doi: 10.1111/j.1600-0447.1970.tb02066.x. No abstract available.

  PMID: 4917967 BACKGROUND

• Barnes TR. A rating scale for drug-induced akathisia. Br J Psychiatry. 1989 May;154:672-6. doi: 10.1192/bjp.154.5.672.

  PMID: 2574607 BACKGROUND

• Girard TD, Pandharipande PP, Carson SS, Schmidt GA, Wright PE, Canonico AE, Pun BT, Thompson JL, Shintani AK, Meltzer HY, Bernard GR, Dittus RS, Ely EW; MIND Trial Investigators. Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: the MIND randomized, placebo-controlled trial. Crit Care Med. 2010 Feb;38(2):428-37. doi: 10.1097/ccm.0b013e3181c58715.

  PMID: 20095068 DERIVED

Related Links

• This is an educational website about ICU delirium

MeSH Terms

Conditions

Delirium; Cognition Disorders; Critical Illness

Interventions

ziprasidone; Haloperidol

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Disease Attributes; Pathologic Processes

Intervention Hierarchy (Ancestors)

Butyrophenones; Ketones; Organic Chemicals

Study Officials

• E Wesley Ely, MD, MPH

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: November 16, 2004
• First Posted: November 17, 2004
• Study Start: December 1, 2004
• Primary Completion: July 1, 2007
• Study Completion: July 1, 2007
• Last Updated: January 29, 2016

Record last verified: 2016-01

Locations

US (5)