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MENDS Study: Trial in Ventilated ICU Patients Comparing an Alpha2 Agonist Versus a Gamma Aminobutyric Acid (GABA)-Agonist to Determine Delirium Rates, Efficacy of Sedation, Analgesia and Discharge Cognitive Status

Information source: Vanderbilt University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Delirium

Intervention: Dexmedetomidine (Drug); Lorazepam (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Vanderbilt University

Official(s) and/or principal investigator(s):
E Wesley Ely, MD, MPH, Principal Investigator, Affiliation: Vanderbilt University

Summary

Delirium has recently been shown as a predictor of death, increased cost, and longer length of stay in ventilated patients. Sedative and analgesic medications relieve anxiety and pain, but may contribute to patients' transitioning into delirium. It is possible that modifying the paradigm for sedation using novel therapies targeted at different receptors, such as dexmedetomidine targeting alpha2 receptors and sparing the GABA receptors, could provide efficacious sedation yet reduce the development, duration, and severity of acute brain dysfunction (delirium).

Clinical Details

Official title: A Randomized, Double-blind Trial in Ventilated ICU Patients Comparing Treatment With an Alpha2 Agonist Versus a Gamma Aminobutyric Acid (GABA)-Agonist to Determine Delirium Rates, Efficacy of Sedation, Analgesia and Discharge Cognitive Status

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Primary outcome: achieving target sedation level

Secondary outcome: duration and severity of delirium

Detailed description: Delirium occurs in 60-80% of ventilated Intensive Care Unit (ICU) patients and is independently associated with prolonged hospital stay, higher cost, a 3-fold increased risk of dying by six months and ongoing neuropsychological dysfunction. Hypothesis: Based on our preliminary work, we hypothesize that standard use of GABA agonist sedatives such as lorazepam and propofol may contribute to ICU delirium and its attendant untoward clinical outcomes. An alternative sedation strategy targeting alpha2 receptors and sparing GABA receptors (dexmedetomidine) might reduce delirium, provide adequate sedation, reduce analgesic requirement, and concurrently improve cognitive performance. Long-term objective: To standardize and compare different strategies of sedation and analgesia for ventilated ICU patients in order to optimize their clinical outcomes focusing on delirium and the long-term neuropsychological dysfunction of ICU survivors. Specific Aims:

- to study prevalence and duration of delirium in critically ill patients using

differential exposure to alpha2 vs. GABA receptor agonists while evaluating efficacy of sedation and analgesia;

- to compare clinical outcomes including duration of mechanical ventilation, ICU length

of stay and severity of neuropsychological dysfunction at hospital discharge; and

- to develop pharmacokinetic and pharmacodynamic models for dexmedetomidine and lorazepam

when used for up to 5 days in ICU patients. Relationship to anesthesiology: We will study whether the adverse clinical outcomes associated with ICU delirium including long-term neuropsychological dysfunction can be modified by the choice of psychoactive agents frequently used by anesthesiologists and intensivists. Design: A blinded, randomized controlled trial of adult mechanically ventilated patients using a sedation strategy of dexmedetomidine ± fentanyl versus lorazepam ± fentanyl, with relevant outcomes and safety monitoring.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Male or female adult patients admitted to the medical and surgical ICU for critical

illnesses requiring mechanical ventilation with expectation of being mechanically ventilated for greater than 24 hours Exclusion Criteria:

- Subjects who are less than 18 years of age

- Subjects who are pregnant (a pregnancy test will be performed on all women of child

bearing age)

- Inability to obtain informed consent from the patient or his/her surrogate

- Subjects in the ICU due to a lack of beds elsewhere in the hospital, triage issues,

or withdrawal of care decisions rather than severity of illness

- Subjects admitted with alcohol or drug overdoses, suicide attempts, or

alcohol/delirium tremens

- Subjects who are physiologically benzodiazepine dependent, and at risk for withdrawal

syndromes

- Subjects with chronic pain syndromes on maintenance narcotics

- Subjects treated within the last 30 days with a drug or device that has not received

regulatory approval as of study entry

- Subjects with a psychiatric history for which they are on neuroleptic treatment

- Subjects with documented moderate to severe dementia

- Subjects with anoxic brain injuries, strokes, neurotrauma, or neuromuscular disorders

such as myasthenia gravis or Guillain Barre syndrome

- Medical team following patient unwilling to use the sedation regimens

- Subjects whose family and/or physician have not committed to aggressive support for

72 hours or who are likely to withdraw within 72 hours

- Subjects who are moribund and not expected to survive 24 hours

- Subjects not expected to survive hospital discharge due to preexisting uncorrectable

medical condition

- Documented allergy to study medications

- Subjects who have either Child-Pugh Class B or C cirrhosis

- Subjects with active coronary artery disease at time of screening as defined by any

recent evidence of ischemia, documented myocardial infarction, or coronary intervention within the past 6 months.

- Subjects with advanced heart block at time of screening

Locations and Contacts

Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States
Additional Information

This is an educational website on delirium in the ICU.

Related publications:

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.

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.

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. Epub 2001 Nov 8.

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.

Inouye SK, Schlesinger MJ, Lydon TJ. Delirium: a symptom of how hospital care is failing older persons and a window to improve quality of hospital care. Am J Med. 1999 May;106(5):565-73. Review.

Inouye SK, Rushing JT, Foreman MD, Palmer RM, Pompei P. Does delirium contribute to poor hospital outcomes? A three-site epidemiologic study. J Gen Intern Med. 1998 Apr;13(4):234-42.

Ostermann ME, Keenan SP, Seiferling RA, Sibbald WJ. Sedation in the intensive care unit: a systematic review. JAMA. 2000 Mar 15;283(11):1451-9. Review.

Marcantonio ER, Juarez G, Goldman L, Mangione CM, Ludwig LE, Lind L, Katz N, Cook EF, Orav EJ, Lee TH. The relationship of postoperative delirium with psychoactive medications. JAMA. 1994 Nov 16;272(19):1518-22.

Dubois MJ, Bergeron N, Dumont M, Dial S, Skrobik Y. Delirium in an intensive care unit: a study of risk factors. Intensive Care Med. 2001 Aug;27(8):1297-304.

Maze M, Scarfini C, Cavaliere F. New agents for sedation in the intensive care unit. Crit Care Clin. 2001 Oct;17(4):881-97. Review.

Stern P, Carstensen L. The Aging Mind: Opportunities in Cognitive Research. National Research Council. Washington, D.C. National Academy of Press. 2000;1st ed:1-249.

Maldonado J, Wysong A, Starre Pvd, Block T. Postoperative Sedation and the Incidence of ICU Delirium in Cardiac Surgery Patients. ASA. 2004;Abstract and Poster Presentation.

Starting date: August 2004
Last updated: June 18, 2014

Page last updated: August 23, 2015

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