The MENDSII Study, Maximizing the Efficacy of Sedation and Reducing Neurological Dysfunction and Mortality in Septic Patients With Acute Respiratory Failure

Description

Ventilated ICU patients frequently have sepsis and the majority have delirium, a form of brain dysfunction that is an independent predictor of increased risk of dying, length of stay, costs, and prolonged cognitive impairment in survivors. Universally prescribed sedative medications—the GABA-ergic benzodiazepines—worsen this brain organ dysfunction. The available alternative sedation regimens, the shorter acting GABA-ergic propofol, and the alpha2 agonist, dexmedetomidine, have both been shown to be superior to benzodiazepines, and yet are different with regard to their effects on innate immunity, bacterial clearance, apoptosis, cognition and delirium. The MENDS II study will compare propofol and dexmedetomidine, and determine the best sedative medication to reduce delirium and improve survival and long-term brain function in our most vulnerable patients— the ventilated septic patient.

Study Start Date

August 2012

Estimated Completion Date

June 2018

Interventions

  • Drug: Propofol
  • Drug: Dexmedetomidine

Specialties

  • Neurology: Critical Care,Neuro/Psych pharmacology
  • Anesthesiology: Airway,Critical Care,Pharmacology/kinetics
  • Pharmacy: Drug Trials,Neuro/Psych pharmacology
  • Emergency Medicine: Airway/Respiratory,Clinical Pharmacology,Infectious Disease,Neurology/Neurosurgery
  • Urgent Care:

MeSH Terms

  • Delirium
  • Dexmedetomidine
  • Propofol
  • Sepsis
  • Toxemia

Study ID

Vanderbilt University -- R01HL111111

Status

Unknown

Trial ID

NCT01739933

Study Type

Interventional

Trial Phase

Phase 3

Enrollment Quota

530

Sponsor

Vanderbilt University

Inclusion Criteria

    Consecutive patients will be eligible for inclusion in the MENDS II study if they are: [1] adult patients (?18 years old) [2] in a medical and/or surgical ICU and [3] on MV and requiring sedation and [4] have severe sepsis (defined as at least 3 systemic inflammatory response (SIRS) criteria as used in the PROWESS study), suspected or known infection (origin and organism data will be collected, when available), and signs of organ dysfunction (since MV is an inclusion criteria, all patients will have at least respiratory failure, but will be assessed for additional renal and cardiovascular organ dysfunctions).

Exclusion Criteria

    Patients will be excluded (i.e., not consented) for any of the following reasons: 1. Rapidly resolving organ failure, indicated by planned immediate discontinuation of MV, at time of screening for study enrollment 2. Pregnant or breastfeeding 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. This exclusion also pertains to mental illnesses requiring long-term institutionalization, acquired or congenital mental retardation, severe neuromuscular disorders, Parkinson's disease, and Huntington's disease. It also excludes patients in coma or with severe deficits due to structural brain diseases such as stroke, intracranial hemorrhage, cranial trauma, malignancy, anoxic brain injury, or cerebral edema. 4. History of 2nd or 3rd degree heart block, bradycardia < 50 beats/minute, pacemaker for bradyarrythmias or uncompensated shock. 5. Benzodiazepine dependency or history of alcohol dependency based on prehospital assessment 6. Active seizures. 7. Expected death within 24 hours of enrollment or lack of commitment to aggressive treatment by family/medical team (e.g., likely to withdraw life support measures within 24 hrs of screening) 8. Inability to understand English or deafness or vision loss that will preclude delirium evaluation 9. Inability to obtain informed consent from an authorized representative within 48 hours of meeting all inclusion criteria, i.e., developing sepsis and qualifying organ dysfunction criteria for the following reasons: 1. Attending physician refusal. 2. Patient and/or surrogate refusal. 3. Patient unable to consent and no surrogate available. 4. 48-hour period of eligibility was exceeded before the patient was screened. 10. Prisoners. 11. Medical team following patient unwilling to use the sedation regimens. 12. Documented allergy to propofol or dexmedetomidine. 13. Current enrollment in a study that does not allow co-enrollment or that uses delirium as a primary outcome. 14. Patients who are on muscle relaxant infusions at time of screening with plans to maintain paralysis >24 hours.

Gender

Both

Ages

18 Years and older

Accepts Healthy Volunteers

No

Study Locations and Contact Information (5)

Study Location Distance Name Phone Email
Baystate Medical Center - Springfield, Massachusetts 78.8 miles Patrick T Mailloux MD 413-794-2419 patrick.mailloux@baystate.org
Henry Ford Health System - Detroit, Michigan 612.3 miles None None None
Baton Rouge General Medical Center - Baton Rouge, Louisiana 1,382.7 miles Hollis R ONeal Jr MD 225-757-4070 honeal@lsuhsc.edu
University of Texas Health Science Center at San Antonio - San Antonio, Texas 1,768.2 miles Antonio R Anzueto MD 210-617-5256 None
University of California San Francisco - San Francisco, California 2,699.8 miles Michael A Gropper MD PhD 415-353-1212 gropperm@anesthesia.ucsf.edu

ClinicalTrialsLocator.com provides clinical trial listings in an easy to view format. All clinical trial information is pulled directly from ClinicalTrials.gov. This website does not guarantee acceptance into any clinical trial, and is not responsible for adverse events that may be incurred from a clinical trial.