Eyecontrol coMmunication Platform for dEliRium manaGemEnt in Intensive Care Units (EMERGE) (EMERGE)

• ClinicalTrials.gov Identifier: NCT06029244
• Recruitment Status: Recruiting
• First Posted: September 8, 2023
• Last Update Posted: March 7, 2024
• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: BIRD (Israel-United States Binational Industrial Research and Development) Foundation- Funding agency; Rabin Medical Center; Assuta Medical Center; Eyefree Assisting Communication Ltd
• Information provided by (Responsible Party): Somnath Bose, MD, Beth Israel Deaconess Medical Center

Study Description

Brief Summary:

The purpose of this research is to investigate whether addition of the EyeControl-Pro platform as an adjunct to standard guideline-based intensive care unit management of critically ill patients is effective in reducing delirium incidence and severity.

Condition or disease	Intervention/treatment	Phase
Delirium; Delirium in Old Age; Critical Illness; Intensive Care Unit Delirium	Device: EyeControl-Pro; Other: Control	Not Applicable

Detailed Description:

This is a prospective, binational, single-blind, multicenter, randomized control trial, conducted according to international good clinical practice (GCP) ethical and quality standards. Critically ill, mechanically ventilated patients aged >=50 years with Richmond Agitation Sedation Scale (RASS) score of -3 to +1 (at time of screening) who are anticipated to require ventilation for >=24 hours will be eligible for recruitment. The study will be conducted simultaneously at Beth Israel Deaconess Medical Center (BIDMC) Boston, USA, Assuta Ashdod Medical Center (Ashdod, Israel) and Rabin Medical Center (Petah Tikvah, Israel) with BIDMC contributing up to 50% of the total enrollment. Participants will be randomized to either a) sham device or b) active intervention arm (details described below). Legally appointed representatives, patients and caregiver teams will be administered an optional questionnaire to assess their experience with the study device at the conclusion of the study protocol. Study subjects will be administered the telephone-Montreal Cognitive Assessment (t-MoCA); total score of 22 - missing 8 points present in Montreal Cognitive Assessment (MoCA) pertaining to drawing/executive function not feasible over phone) or MoCA (if still in-hospital; assessed out of total score of 30) and Hospital Anxiety and Depression Scale (HADS) questionnaire 30 days post-randomization. Hebrew versions of these questionnaires will be used at Israeli sites.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 160 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Study participants will be randomized to either a) EyeControl-Pro assisted active intervention arm or b) sham control
• Masking: None (Open Label)
• Masking Description: Patients will be unblinded, or unmasked, to treatment allocation given the nature of the intervention.
• Primary Purpose: Treatment
• Official Title: Eyecontrol coMmunication Platform for dEliRium manaGemEnt in Intensive Care Units (EMERGE) : A Multicenter Randomized Controlled Trial
• Actual Study Start Date: March 1, 2024
• Estimated Primary Completion Date: April 30, 2025
• Estimated Study Completion Date: May 31, 2025

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: EyeControl-Pro assisted active intervention arm; The device will be placed on patient's heads. Once the device is properly positioned, patient's will undergo a training session/tutorial lasting 2-3 minutes to orient them to the device usage. Personalized family messages recorded by LARs or others will be played at regular intervals up to 5 times per day (between 08:00-18:00) (8 am to 6 pm). Personalized music/brown noise will be played for 15 minutes every 4 hours, which will be modulated according to your reactions/choices. A study team member will assess patient's mental status by asking thinking and memory questions twice a day (AM and PM). The device will perform the same assessments within 30 minutes of those performed by the study team. The device will be removed at 1800/2000 hrs to ensure adequate sleep. Patient's will be in this study arm for up to 7 days of start of study. The device will be removed on day 7 or sooner if patient's do not need ventilator support and standard care will continue as before device usage.	Device: EyeControl-Pro; Based on artificial intelligence (AI)-powered eye-tracking technology, the EyeControl-Pro wearable device and smart platform enable 24/7 customizable communication and monitoring between ventilated patients who cannot speak, their families, and medical teams
Sham Comparator: Sham Control; The device will be placed on patient's heads. Once the device is properly positioned, patient's will undergo a training session/tutorial lasting 2-3 minutes to orient them to the device usage. Patient's will not receive any of the orientation or family messages and no music will be played through the earphones of the device. A study team member will assess patient's mental status by asking thinking and memory questions twice a day (AM and PM). The device will perform the same assessments within 30 minutes of those performed by the study team. The device will be removed at 1800/2000 hrs to ensure adequate sleep. Patient's will be in this study arm for up to 7 days of start of study. The device will be removed on day 7 or sooner if patient's do not need ventilator support and standard care will continue as before device usage.	Other: Control; No intervention

Outcome Measures

Primary Outcome Measures :

1. Prevalence of CAM ICU+ assessments during the first 7 days in ICU post-randomization or ICU discharge/death (whichever is sooner) [ Time Frame: Upto 7 days or liberation from ventilator whichever is sooner. ]
   To evaluate if study subjects randomized to active EyeControl-Pro arm have a higher proportion of delirium free assessments as assessed by CAM (confusion assessment method)-ICU during device usage for up to 7 days when compared with those in the sham EyeControl-Pro arm. CAM-ICU is a validated assessment tool for detection of ICU delirium.

Secondary Outcome Measures :

1. Prevalence of severe delirium assessments (defined as CAM ICU 7>6) during the first 7 days in ICU post-randomization or ICU discharge/death (whichever is sooner) [ Time Frame: Upto 7 days or discharge from intensive care unit (ICU) whichever is sooner ]
   To evaluate if study subjects in the active EyeControl-Pro arm have lower prevalence of severe delirium assessments as measured by CAM-ICU7 within first 7 days post randomization or ICU discharge (whichever is sooner) when compared to sham control arm. CAM-ICU 7 is a validated instrument for measurement of delirium severity with scores ranging from 0-7.
2. Mean number of days with delirium (defined as the total number of days with at least one CAM ICU positive delirium assessment) within 7 days post-randomization or up to discharge from the ICU/death, whatever occurs earlier. [ Time Frame: Upto 7 days or discharge from intensive care unit (ICU) whichever is sooner ]
   To evaluate if subjects randomized to the active EyeControl-Pro arm have lower delirium incidence (as measured by CAM-ICU) within first 7 days post randomization or ICU discharge whichever is sooner when compared to sham EyeControl-Pro arm.

Other Outcome Measures:

1. Cognitive scores [ Time Frame: 30 days post-randomization. ]
   To compare cognitive function at 30 days post enrollment using the t-MoCA (telephone-Montreal Cognitive Assessment) or MoCA (if still in-hospital) questionnaire. MoCA is a validated instrument for assessment of cognition with range 0-30 (0-22 for telephonic version) score of over 26 indicates normal.
2. Depression anxiety scores [ Time Frame: 30 days post-randomization. ]
   To compare depression and anxiety scores at 30 days post enrollment using the HADS (Hospital Anxiety and Depression Scale) questionnaire.HADS ranges from 0-21 with higher scores indicating worse depression or anxiety
3. CAM ICU concordance [ Time Frame: During device usage upto 7 days ]
   Agreement between CAM ICU assessment between Eyecontrol and investigator administered CAM-ICU in active intervention arm
4. Cumulative dose of sedatives [ Time Frame: During device usage or upto 7 days whichever is sooner ]
   Dose of intravenous sedatives between 2 groups (in mgs/mcgs)
5. Days free of restraints [ Time Frame: Upto 7 days or discharge from intensive care unit ]
   Comparison of days free of restraints between 2 groups
6. Use of rescue medications for delirium and agitation [ Time Frame: Upto 7 days or discharge from intensive care unit ]
   Use of medications for agitated delirium
7. ICU days alive and free of delirium and coma [ Time Frame: Upto 7 days or discharge from intensive care unit (ICU) whichever is sooner ]
   To evaluate if subjects randomized to the active EyeControl-Pro arm have higher number of days free of coma and delirium within first 7 days post randomization or ICU discharge whichever is sooner when compared to sham EyeControl-Pro arm

Eligibility Criteria

• Ages Eligible for Study: 50 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Mechanically ventilated patients aged >=50 years
• RASS score of -3 to +1 and
• Anticipated to require >=24 hours of mechanical ventilation

Exclusion Criteria:

• Not expected to survive >=24 hours
• Have limitations in care (Do Not Resuscitate, or comfort-focused care orders)
• Receiving paralytic neuromuscular blocking agent (NMBA) infusion or anticipated need for NMBA use
• Have advanced dementia or cognitive impairment including post-concussive syndrome.
• Have acute or subacute neurological disorders.
• Have severe uncorrected psychiatric disorders.
• Have uncorrected hearing or visual impairment.
• Have an unstable cervical spine or collar in place limiting movement.
• Enrolled in a clinical trial which prohibits co-enrollment.
• Incarcerated
• Have no identified legally appointed representative (LAR)
• Are unable to communicate in the predominant local language (English at US site and Hebrew in Israel)
• Refusal of treating clinical team.

Contacts and Locations

Contacts

Contact: Alkanada Behera; 617-667-7000; abehera@bidmc.harvard.edu

Contact: Van Nguyen, BS; 617-632-8065; vnguye17@bidmc.harvard.edu

Locations

United States, Massachusetts

Beth Israel Deaconess Medical Center; Recruiting

Boston, Massachusetts, United States, 02215

Contact: Somnath Bose, MD 617-667-7000 sbose2@bidmc.harvard.edu

Israel

Assuta Ashdod Medical Center; Not yet recruiting

Ashdod, Israel

Contact: Ami Mayo, MD

Rabin Medical Center; Not yet recruiting

Petah tikva, Israel

Contact: Itai Ben David, MD

Sponsors and Collaborators

Beth Israel Deaconess Medical Center

BIRD (Israel-United States Binational Industrial Research and Development) Foundation- Funding agency

Rabin Medical Center

Assuta Medical Center

Eyefree Assisting Communication Ltd

Investigators

• Principal Investigator: Somnath Bose, MD; Beth Israel Deaconess Medical Center

More Information

Publications:

Girard TD, Pandharipande PP, Ely EW. Delirium in the intensive care unit. Crit Care. 2008;12 Suppl 3(Suppl 3):S3. doi: 10.1186/cc6149. Epub 2008 May 14.

Mart MF, Williams Roberson S, Salas B, Pandharipande PP, Ely EW. Prevention and Management of Delirium in the Intensive Care Unit. Semin Respir Crit Care Med. 2021 Feb;42(1):112-126. doi: 10.1055/s-0040-1710572. Epub 2020 Aug 3.

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. doi: 10.1001/jama.291.14.1753.

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. doi: 10.1007/s00134-001-1132-2. Epub 2001 Nov 8.

Pandharipande PP, Girard TD, Jackson JC, Morandi A, Thompson JL, Pun BT, Brummel NE, Hughes CG, Vasilevskis EE, Shintani AK, Moons KG, Geevarghese SK, Canonico A, Hopkins RO, Bernard GR, Dittus RS, Ely EW; BRAIN-ICU Study Investigators. Long-term cognitive impairment after critical illness. N Engl J Med. 2013 Oct 3;369(14):1306-16. doi: 10.1056/NEJMoa1301372.

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. doi: 10.1097/01.ccm.0000119429.16055.92.

Smith CD, Grami P. Feasibility and Effectiveness of a Delirium Prevention Bundle in Critically Ill Patients. Am J Crit Care. 2016 Dec;26(1):19-27. doi: 10.4037/ajcc2017374.

Kinchin I, Mitchell E, Agar M, Trepel D. The economic cost of delirium: A systematic review and quality assessment. Alzheimers Dement. 2021 Jun;17(6):1026-1041. doi: 10.1002/alz.12262. Epub 2021 Jan 21.

Hayhurst CJ, Pandharipande PP, Hughes CG. Intensive Care Unit Delirium: A Review of Diagnosis, Prevention, and Treatment. Anesthesiology. 2016 Dec;125(6):1229-1241. doi: 10.1097/ALN.0000000000001378.

Pun BT, Badenes R, Heras La Calle G, Orun OM, Chen W, Raman R, Simpson BK, Wilson-Linville S, Hinojal Olmedillo B, Vallejo de la Cueva A, van der Jagt M, Navarro Casado R, Leal Sanz P, Orhun G, Ferrer Gomez C, Nunez Vazquez K, Pineiro Otero P, Taccone FS, Gallego Curto E, Caricato A, Woien H, Lacave G, O'Neal HR Jr, Peterson SJ, Brummel NE, Girard TD, Ely EW, Pandharipande PP; COVID-19 Intensive Care International Study Group. Prevalence and risk factors for delirium in critically ill patients with COVID-19 (COVID-D): a multicentre cohort study. Lancet Respir Med. 2021 Mar;9(3):239-250. doi: 10.1016/S2213-2600(20)30552-X. Epub 2021 Jan 8. Erratum In: Lancet Respir Med. 2021 Jan 27;:

Nikooie R, Neufeld KJ, Oh ES, Wilson LM, Zhang A, Robinson KA, Needham DM. Antipsychotics for Treating Delirium in Hospitalized Adults: A Systematic Review. Ann Intern Med. 2019 Oct 1;171(7):485-495. doi: 10.7326/M19-1860. Epub 2019 Sep 3.

Neufeld KJ, Yue J, Robinson TN, Inouye SK, Needham DM. Antipsychotic Medication for Prevention and Treatment of Delirium in Hospitalized Adults: A Systematic Review and Meta-Analysis. J Am Geriatr Soc. 2016 Apr;64(4):705-14. doi: 10.1111/jgs.14076. Epub 2016 Mar 23. Erratum In: J Am Geriatr Soc. 2016 Oct;64(10 ):2171-2173.

• Responsible Party: Somnath Bose, MD, Assistant Professor of Anesthesia, Harvard Medical School, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT06029244
• Other Study ID Numbers: 2023P000563
• First Posted: September 8, 2023
• Last Update Posted: March 7, 2024
• Last Verified: March 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Delirium; Critical Illness; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Disease Attributes; Pathologic Processes