Phase 3
N=422
The MENDS2 Study, Maximizing the Efficacy of Sedation and Reducing Neurological Dysfunction and Mortality in Septic Patients With Acute Respiratory Failure
Sepsis · Delirium · Impaired Cognition
Bottom Line
View on ClinicalTrials.gov: NCT01739933 ↗Enrolled (actual)
422
Serious AEs
0.0%
Results posted
Jun 2021
Primary outcome: Primary: Delirium/Coma Free Days (DCFDs) — 8; 7.5 days
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Dexmedetomidine (Drug); Propofol (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Vanderbilt University Medical Center
- Primary completion
- Jul 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Delirium/Coma Free Days (DCFDs) |
8; 7.5 | — |
| SECONDARY Ventilator-free Days (VFDs) |
20.9; 19.9 | — |
| SECONDARY Death at 90 Days |
81; 82 | — |
| SECONDARY Cognitive Function Utilizing the Telephone Interview for Cognitive Status Total (TICS-T) |
39; 38 | — |
Summary
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 MENDS2 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.
Eligibility Criteria
Inclusion Criteria
Consecutive patients will be eligible for inclusion in the MENDS2 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 suspected or known infection
Exclusion Criteria
Patients will be excluded (i.e., not consented) for any of the following reasons:
- Rapidly resolving organ failure, indicated by planned immediate discontinuation of MV, at time of screening for study enrollment
- Pregnant or breastfeeding
- 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.
- History of 2nd or 3rd degree heart block, bradycardia 48 hours.
- Greater than 96 hours on mechanical ventilation prior to meeting all inclusion criteria.
Data sourced from ClinicalTrials.gov (NCT01739933). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.