Hexalog: A Rapid-Acting Ultra-Concentrated Insulin Formulation

DESCRIPTION (provided by applicant): Our overall objective is to develop a novel monitor, OptiSED, for the precise and continuous assessment of sedation in the ICU. The specific Phase I goals of this 12-month project are to: 1) develop an objective score for continuous monitoring of sedation status in ICU patients, and 2) perform an initial assessment of its validity. This scor will be integrated in the OptiSED monitor, which will allow delivery of patient-customized ICU sedation and address the unmet needfor an effective sedation management in critically ill. The OptiSED ICU sedation score will be based on the advanced signal processing of EEG signals and will closely agree with the extensively validated and widely-used Richmond Agitation Sedation Scale (RASS). The rationale for developing OptiSED is to facilitate wider implementation of clinical ICU sedation protocols shown to significantly improve outcomes in critically ill and reduce care costs. These protocols minimize the adverse effects of poorly controlled sedation by aiming to administer the sedation therapy more accurately and according to patient-specific needs. To achieve this goal, frequently repeated assessments of the patient's level of sedation are essential. Currently, there are a number of clinical sedation scores, among which the RASS has shown excellent validity and inter-rater reliability in broad range of ICU patients. However, these subjective scores provide only sporadic patient assessments and require significant increase in resourcesfor their frequent administration. Also, they cannot be applied to certain subgroups of ICU patients. Thus, despite strong recommendations by the Society of Critical Care Medicine that sedation protocols be used to manage sedation in the ICU, survey datasuggest their actual usage has been disappointingly low . The OptiSED would alleviate the above limitations of clinical sedation scores by providing an automated, readily available measurement of ICU sedation depth. This Phase I will focus on the development and initial validation of the EEG-based OptiSED score for ICU sedation. Significant portion of this 12-month program will be dedicated to clinical work to be performed at a leading national clinical research institution, where ICU-specific data will becollected in two stages to derive the OptiSED score and perform its initial validation. To derive the OptiSED score, we will adapt our proven and patented signal processing methods for real-time EEG analysis, which are integrated in our commercial intraoperative brain monitor - NeuroSENSE(R). The specific aims of this Phase I project are: (1) To carry out a pilot observational clinical study in ICU patients undergoing sedation and acquire continuous EEG signals and clinical RASS sedation scores at predefined time intervals; (2) To derive the objective EEG-based OptiSED score to match the clinical RASS observations by adapting our proven wavelet-based EEG analysis using ICU- specific data collected in (1); (3) To preliminary validate the OptiSED score by acquiring additional clinical data (paired EEGs and RASS) from ICU patients and using known validation methods for clinical instruments. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Virtually every patient admitted to the ICU is administered sedation therapy to enable treatment delivery and provide comfort necessary for healing. Adequate sedation in the ICU remains a challenge since there is no means for its direct assessment, while both under- and over-sedation have harmful consequences for these vulnerable patients. The overall goal of this project is to develop and validate the EEG-based OptiSED monitor for continuous and objective measurement of ICU sedation levels, so as to enable wider implementation of sedation protocols shown to lead tosignificant improvements in patient outcomes and care costs.