Acute Neurological ICU Sedation Trial (ANIST)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Daniel Hanley, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT00390871
First received: October 19, 2006
Last updated: April 11, 2013
Last verified: April 2013
  Purpose

Dexmedetomidine (Precedex, Hospira) is a "super" selective alpha2-agonist - 8-10x more avid binding to alpha2 receptors than clonidine - and may have particularly favorable characteristics as a continuous i.v. infusion sedative for critically ill neuroscience patients. Its combination of anxiolysis, analgesia, without undue lethargy may make it an ideal agent where frequent neurological examinations are important (12). Unclear, however, is whether Precedex is superior to current common i.v. sedation protocols, and if there are any undue concerns of this agent on cerebral physiology and cortical stimulation.


Condition Intervention Phase
Sedation
Drug: Precedex
Drug: Propofol
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Acute Neurological ICU Sedation Trial (ANIST)

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Johns Hopkins Adapted Cognitive Exam [ Time Frame: day of study ] [ Designated as safety issue: No ]
    Cognitive assessment tool

  • Confusion Assessment Method for the Intensive Care Unit [ Time Frame: day of study ] [ Designated as safety issue: No ]
    CAM-ICU delirium assessment tool

  • Time from initiation of study drug to calm, non-anxious state [ Time Frame: day of study ] [ Designated as safety issue: No ]
    From control state to RASS Score or 0 to -1 (average=137 min)


Secondary Outcome Measures:
  • Therapy Intensity Level Scale (TIL) [ Time Frame: day of study ] [ Designated as safety issue: No ]
    Bedside assessment tool to quantify nursing effort

  • Requirement for fluids, pressors [ Time Frame: day of study ] [ Designated as safety issue: Yes ]
    Documenting need for adjunctive treatment with vasoactive agents

  • Toxicity/side effects [ Time Frame: day of study ] [ Designated as safety issue: Yes ]
    documenting drug toxicity - rash, angioedema, nausea, fever, etc.

  • Numerical Pain Rating Scale [ Time Frame: day of study ] [ Designated as safety issue: No ]
    behavioral and numerical pain rating

  • Need for less or more fentanyl during the infusion drug phase [ Time Frame: day of study ] [ Designated as safety issue: No ]
    assessemnt of fentanyl dosing required to maintain behavioral pain score at < 3


Enrollment: 60
Study Start Date: April 2005
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Fentanyl/Propofol sedation
Patient sedated with fentanyl/propofol as needed to RASS Score 0 to -1
Drug: Propofol
Active Comparator: Fentanyl/Dexmedetomidine sedation
Patient sedated with fentanyl/dexmedetomidine as needed to RASS Score 0 to -1
Drug: Precedex

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Study 1: Inclusion Criteria:

Neuroscience patients in the NCCU who are:

  1. 18-80 years of age;
  2. Mechanically ventilated patients;
  3. Requiring continuous sedation for a minimum of 9-11 hours (depending on whether or not pt is post-operative), yet frequent neurological examinations or Patients with a NICSS score > 0
  4. Patient or family able to provide consent.
  5. Considered to have guarded yet stable neurological state. Not fluctuating intracranial pressure (ICP), cerebral perfusion pressure (CPP), or ongoing known cerebral ischemia if ICP monitoring in place.

Study 1: Exclusion Criteria:

  1. Pregnancy.
  2. ICP> 30 mm Hg despite therapy if ICP monitored.
  3. CPP <70 mm Hg if monitored.
  4. Occurrence of: new cerebral stroke, hemorrhage, or change in edema by CT, increase in ICP if monitored.
  5. Neuromuscular paralysis.
  6. Non-functional cognitive exam - not following commands.
  7. Renal insufficiency: Serum Creatinine >2.0 mg/dl or estimated Cr Clearance <40.0 ml/min.
  8. Hepatic disease: AST, ALT > 300, or INR > 1.7 not on anticoagulants.
  9. Severe COPD with baseline arterial pCO2>50.
  10. Suspected alcohol or substance withdrawal.
  11. Hypotension - requiring pressor therapy to maintain baseline adequate CPP or mean arterial pressure.
  12. Cardiac arrhythmia - sinus bradycardia (HR <60), atrial fibrillation (>6 PVC's/min)
  13. Bradycardia- heart rate less than 60 beats per minute.
  14. Patient does not require mechanical ventilation.

Study 2: Inclusion Criteria:

Critically ill neuroscience patients who are:

  1. 18-80 years of age;
  2. Mechanically ventilated;
  3. Require Intracranial Pressure (ICP) monitoring by either subarachnoid bolt (SA bolt), or by an Intra-Ventricular Catheter (IVC).
  4. Amenable for placement of intra-cerebral oxygen sensor or jugular bulb catheter.
  5. Have GCS score > 5 that requires sedation.
  6. Requiring continuous sedation for minimum of 9-11 hours (depending on whether or not pt is post-operative) , yet frequent neurological examinations every 1-2 hours or Patients with a NICSS score > 0
  7. Patient or family able to provide consent.

Study 2: Exclusion Criteria:

  1. Pregnancy;
  2. ICP> 30 mm Hg despite therapy;
  3. CPP <70 mm Hg;
  4. Occurrence of: new cerebral stroke, hemorrhage, or change in edema by CT, increase in ICP if monitored.
  5. Continuous neuromuscular paralysis
  6. Renal insufficiency: Serum Creatinine >2.0 mg/dl or estimated Cr <40.0 Clearance ml/min.
  7. Hepatic disease: AST, ALT > 300, or INR > 1.7 not on anticoagulants.
  8. Severe COPD with baseline arterial pCO2>50.
  9. Suspected alcohol or substance withdrawal.

Study 3: Inclusion Criteria:

Critically ill neuroscience patients who are:

  1. 18-80 years of age;
  2. Requiring continuous sedation for minimum of 9-11 hrs (depending on whether or not pt is post-operative), yet frequent neurological examinations or Patients with a NICSS score >0
  3. Patient or family able to provide consent.
  4. Mechanically ventilated patients;
  5. Considered to have guarded yet stable neurological state. Not fluctuating ICP, CPP, or ongoing known cerebral ischemia.
  6. Presence of intra-operatively placed GRID electrode array or patients requiring continuous EEG monitoring.

Study 3: Exclusion Criteria:

  1. Pregnancy
  2. Occurrence of: new cerebral stroke, hemorrhage, or change in edema by CT, increase in ICP if monitored.
  3. Continuous neuromuscular paralysis
  4. Renal insufficiency: Serum Creatinine >2.0 or Cr Clearance <40.0
  5. Hepatic insufficiency: AST, ALT> 300, or PT time > 1.7 not on anticoagulants.
  6. Severe COPD with baseline arterial pCO2>50.
  7. Suspected alcohol or substance withdrawal.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00390871

Locations
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Daniel Hanley
Investigators
Principal Investigator: Marek Mirski, MD, PhD Johns Hopkins University
  More Information

No publications provided

Responsible Party: Daniel Hanley, Professor, Acute Care Neurology, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00390871     History of Changes
Other Study ID Numbers: ANIST
Study First Received: October 19, 2006
Last Updated: April 11, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Johns Hopkins University:
Patient
Must be
Under

Additional relevant MeSH terms:
Propofol
Dexmedetomidine
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014