Clinical Research Directory

40 Hz Gamma Auditory Stimulation for Delirium Prevention in Critically Ill ICU Patients

Delirium is a common acute disturbance of attention and cognition among critically ill patients and is associated with prolonged mechanical ventilation, longer hospital stays, and increased mortality. This multicenter, quadruple-masked, randomized controlled trial will evaluate whether 40 Hz gamma auditory stimulation can help prevent delirium in mechanically ventilated adult ICU patients. A total of 142 participants aged 50 years or older who are expected to require mechanical ventilation for at least 48 hours will be randomly assigned in a 1:1 ratio to receive either 40 Hz gamma auditory stimulation or a silent audio track, in addition to standard ICU care. The assigned intervention will be delivered through identical earphones twice daily at 08:00 and 20:00, for 60 minutes per session, until extubation or Day 7 after randomization, whichever occurs first. The primary outcome is the number of delirium- and coma-free days during the first 7 days after randomization. Secondary outcomes include the incidence and duration of delirium during this period, duration of mechanical ventilation, length of ICU and hospital stay through Day 28, and 28-day all-cause mortality.

Reducing Days DELirious With DEXmedetomidine as Part of an Intensive Care Unit Sleep Promotion Bundle

Patients frequently experience problems with sleep while admitted to the ICU. Good sleep is important in ensuring that your immune system responds properly to infection, for your heart to function optimally, and to support normal brain function such as memory. To address sleep problems in the ICU, a bundle of interventions to support more normal sleep are provided. These bundles consist of medications such as sedatives and environmental changes such as less frequent times being assessed overnight and noise reduction strategies. Although medications can make patients appear to be sleeping, most medications do not provide patients with restful sleep. More research is needed on medications that better mimick restful sleep. One such medication is dexmedetomidine. When formally measured dexmedetomidine can make sleep appear more like a patient sleeping at home as compared to the hospital. The purpose of this study is to test whether giving a patient in the intensive care unit dexmedetomidine helps have a more restful sleep and possibly be more alert and/or interactive the next day. To see if dexmedetomidine improves sleep, the investigators will compare the quality of sleep of two different groups of participants: one group that receives dexmedetomidine at night for 2 nights in a row and another group that does not. How well one sleeps will be measured, in either group, will be assessed by a portable sleep machine that is attached by several stickers. This study is called a pilot or feasibility study. A pilot study assesses how easy it is to recruit patients, whether the sleep machine is tolerated, and amount of time sleep is measured. It is anticipated that about 50 people will take part in this study. This study should take approximately 2 years to complete, and the results should be known in about 1-2 years thereafter.

Delirium Phenotypes and Subsequent Impairment During Transition From ICU to Hospital Wards

The goal of this observational study is to learn about the disability profile during transition from ICU to hospital wards of delirium patients, including cognitive impairment, physical dysfunction and psychological disorders. The main question it aims to answer is: * What is the main rehabilitation problem during transition from ICU to hospital wards for patients who experienced ICU delirium? * Dose different phenotypes of ICU delirium shows different rehabilitation problem during ICU transition? Participants will be followed up and assessed by questionnaires after discharge from ICU to hospital wards until hospital discharge.

Lemborexant for Sleep and Delirium Prevention in Elderly ICU Patients

Sleep disturbance is very common among critically ill patients in the intensive care unit (ICU), particularly in older adults after surgery. Poor sleep in the ICU is associated with important complications, including delirium, longer duration of mechanical ventilation, prolonged hospital stay, and increased mortality. Current non-drug approaches to improve sleep, such as reducing noise and light and clustering nursing care, may provide limited benefit and are often difficult to implement consistently. Safe and effective drug treatments for sleep in critically ill older patients remain limited. Lemborexant is a dual orexin receptor antagonist that promotes sleep by blocking wake-promoting pathways in the brain. Unlike many traditional sleep medications, lemborexant has minimal effects on breathing and has been shown to be well tolerated in older adults with insomnia. However, its effects on sleep and delirium have not been studied in critically ill patients. This study is a single-center, randomized, double-blind, placebo-controlled feasibility and pilot trial conducted in the surgical intensive care unit of Siriraj Hospital, Bangkok, Thailand. The study will enroll 100 critically ill postoperative patients aged 65 years or older who are expected to remain in the ICU for at least 48 hours. Participants will be randomly assigned to receive either low-dose lemborexant (2.5 mg) or a matching placebo once nightly for three consecutive nights. All participants will also receive standard non-pharmacologic sleep-promoting care used in the ICU. The main goals of this pilot study are to evaluate the feasibility and safety of administering lemborexant in elderly ICU patients and to explore its potential effects on sleep and delirium. Sleep will be assessed using both subjective questionnaires completed each morning and objective wrist-worn actigraphy to measure sleep duration and sleep stages. Delirium will be assessed twice daily using a standardized delirium screening tool for up to seven days or until ICU discharge. Additional outcomes include medication adherence, adverse events, duration of mechanical ventilation, length of ICU and hospital stay, and in-hospital mortality. The results of this study will provide important preliminary data on the feasibility, safety, and potential benefits of lemborexant in critically ill older adults and will help inform the design of future larger clinical trials aimed at improving sleep and reducing delirium in the ICU.

CTSN Embolic Protection Trial

This is a prospective, multi-center, randomized effectiveness trial of the CardioGard Embolic Protection Cannula in high-risk valve surgery patients.

Behavioral Economic & Staffing Strategies in the ICU

The overarching goal of this study is to support the "real world" assessment of strategies used to foster adoption of several highly efficacious evidence-based practices in healthcare systems that provide care to critically ill adults with known health disparities. Investigators will specifically evaluate two discrete strategies grounded in behavioral economic and implementation science theory (i.e., real-time audit and feedback and registered nurse implementation facilitation) to increase adoption of the ABCDEF bundle in critically ill adults.

Neurosteer Bedside Monitoring System

The purpose of this study is to evaluate the clinical utility of Neurosteer's brain monitoring platform for monitoring delirium, sedation, and agitation in intubated and sedated ICU patients. The research team will be conducting a single-site study. The research team will enroll 100 patients admitted to the NSICU. 50 of these patients will have Acute Neurological Injuries (ANI) and the other 50 will not have an ANI. All enrolled patients will receive the intervention, the Neurosteer brain monitoring device. The study intervention consists of the use of Neurosteer's innovative single-channel EEG monitoring device to determine if there is a good correlation and agreement between their signals/parameters to RASS, CAM-ICU, and continuous EEG monitoring readings. The Neurosteer device will be attached to their forehead and readings will be collected for the duration of their NSICU stay. The research team will adapt the current physical methods of detecting the depth of anesthesia i.e. through the Richmond Agitation-Sedation Scale (RASS) \& CAM-ICU, to auditory stimulation, which will be delivered through earphones with no physical contact, with the aim of achieving a high correlation between the methods. RASS and CAM-ICU will be collected hourly as standard of care and Neurosteer auditory stimulation will be done 3-4 times a day to coincide with RASS and 1-2 times a day to coincide with CAM-ICU. The research team will correlate collected hourly RASS and CAM-ICU assessments with Neurosteer derived signals and parameters.

pEEG Monitoring Effect on Delirium, Ventilator Days, and PICS

The goal of this multi-site observational study is to compare delirium rates, days on mechanical ventilation, and Post Intensive Care Syndrome (PICS) rates in adult Intensive Care Unit (ICU) patients. The study will examine patients whose sedation and analgesia infusion titration is managed with both Richmond Agitation and Sedation Scale (RASS) and Processed Electroencephalography (pEEG) monitoring vs patients who receive RASS monitoring alone. The main questions are: * Compared to RASS monitoring method alone, does the use of 4 channel pEEG monitor in conjunction with RASS to guide the management of sedation and analgesic in patients who are ventilated reduce the average number of delirium days, measured by Intensive Care Delirium Screening Checklist (ICDSC)? * To determine when compared to RASS monitoring alone if the use of 4 channel pEEG monitor in conjunction with RASS to guide the management of Intravenous (IV) sedation and analgesia in ventilated patients reduces the days a patient spends on a mechanical ventilator when compared to RASS only monitoring from retrospective data. * To determine when compared to RASS monitoring method alone, does the use of 4 channel pEEG monitor in conjunction with RASS experience lower doses of sedation and analgesia infusions? * To determine when compared to RASS monitoring method alone, does the use of 4 channel pEEG monitor in conjunction with RASS experience less incidence and duration of PICS?

Minimizing ICU Neurological Dysfunction With Dexmedetomidine-induced Sleep (MINDDS II)

This is a pragmatic phase III, randomized, blinded, double placebo-controlled, three-arm trial of elderly patients following cardiac surgery to assess the relationship between nighttime intravenous (IV) and sublingual dexmedetomidine on postoperative delirium and functional outcomes after surgery.

Haloperidol With or Without Chlorpromazine in Treating Delirium in Patients With Advanced, Metastatic, or Recurrent Cancer

This randomized phase II/III trial studies how well haloperidol with or without chlorpromazine works in treating delirium in patients with cancer that has spread to other parts of the body or has come back. Haloperidol and chlorpromazine may control the symptoms of delirium (loss of contact with reality) in patients with cancer.

Goal-Directed Sedation in Mechanically Ventilated Infants and Children

Ventilated pediatric patients are frequently over-sedated and the majority suffer from delirium, a form of acute brain dysfunction that is an independent predictor of increased risk of dying, length of stay, and costs. Universally prescribed sedative medications-the GABA-ergic benzodiazepines-worsen this brain organ dysfunction and independently prolong duration of ventilation and ICU stay, and the available alternative sedation regimen using dexmedetomidine, an alpha-2 agonist, has been shown to be superior to benzodiazepines in adults, and may mechanistically impact outcomes through positive effects on innate immunity, bacterial clearance, apoptosis, cognition and delirium. The mini-MENDS trial will compare dexmedetomidine and midazolam, and determine the best sedative medication to reduce delirium and improve duration of ventilation, and functional, psychiatric, and cognitive recovery in our most vulnerable patients-survivors of pediatric critical illness.

Light and Noise: Objectively Assessing Environmental Risk Factors for Delirium in the ICU

Recognition of delirium as a medical entity with relevance to both morbidity and mortality, especially in critically ill patients, is a relatively recent development. However, research into delirium prevention and treatment is now in focus of scientific efforts internationally. Knowledge of intensive care unit (ICU) environment as a potential modifiable risk factor for delirium is insufficient to this date. This study thus seeks to evaluate, whether potentially modifiable environmental factors, such as noise or dazzling, are associated with development of delirium. Knowledge derived from this investigation could change both the process of care provision in intensive care units as well as the design of ICUs in general in the future. This project is planned to be carried out as an observational pilot study at three perioperative ICUs at the University Medical Centre Graz. Adult patients shall be screened for inclusion, if not deeply sedated. Suitable patients shall be included into the study after written informed consent or deferred consent if they can be expected to remain in the ICU for at least another two days, if they are not already in delirium, if the ICU environment is not actively modified for therapeutic reasons and if no treatment limitations are in place. Over a study duration of one year, 250 to 300 patients are expected to be enrolled into the study. Of those, 60 to 120 patients are likely to develop delirium. Baseline data known to be of relevance for outcome prediction in critically ill patients and factors known to predispose for development of delirium during ICU and hospital stay will be collected. Study equipment will be deployed to measure noise levels and illumination repeatedly over the day. Daily assessments for delirium using the Confusion Assessment Method in Intensive Care Units (CAM-ICU) will be performed. Vital status, physiologic parameters and parameters of ongoing treatment will concomitantly be documented on a daily basis. Data on light and noise levels are then to be unified with parameters of physiology and treatment, vital status, and results of daily assessments for delirium. Statistical analysis using methods of descriptive and comparative statistics as well as both unadjusted and adjusted logistic regression analysis will be performed to identify factors significantly associated with the development of delirium (i.e., risk factors).

CITADEL: Effectiveness of CITicoline in Preventing Cognitive Decline After DELirium

The aim of this study is to assess whether citicoline (TRAUSAN), a neuroprotective agent involved in membrane phospholipid synthesis and neurotransmission, can prevent or attenuate cognitive decline in older adults who develop perioperative delirium during hospitalization for proximal hip fracture. Delirium is a frequent and severe complication in this population and is associated with cognitive and functional deterioration, institutionalization, and mortality. Participants will be randomly assigned (1:1) to receive citicoline 1000 mg/day for 6 months after discharge, or usual care. Cognitive and functional status will be evaluated at discharge and subsequently at 3 and 6 months follow-up visits.

Evaluating Novel Healthcare Approaches to Nurturing and Caring for Hospitalized Elders

The goal of this clinical trial is to compare the Hospital Elder Life Program (HELP) with a family-augmented version of HELP (FAM-HELP), that includes family members and care partners, for the prevention of delirium in older patients during hospital admission. The main objectives of the trial are the following: 1. To compare the effectiveness of FAM-HELP and HELP in reducing both the incidence of delirium and its severity. 2. To compare the effectiveness of FAM-HELP and HELP in improving patient- and family-reported outcomes. 3. To explore the implementation context, process, and outcomes of the FAM-HELP program in diverse hospital settings.

Intraoperative Midazolam on Delirium Outcome of Elderly Patients

This study was a multicenter, randomized, double-blind, placebo-controlled trial to treat elderly surgical patients with low-dose midazolam or placebo for anesthesia induction. The incidence of postoperative 7-day delirium was assessed and compared between two groups, to provide valuable reference for clinical practitioners in the use of midazolam in elderly surgical patients.

DElirium and LIGHT: Exploring Modifiable Risk Factors of Delirium - a Pilot Study

After a period of critical illness many people develop problems with memory, attention and thinking and this can make daily life more difficult. A risk factor for these problems is delirium. Delirium is a sudden change in the brain that causes confusion and difficulty focusing. People develop delirium when they are sick for another reason, such as a severe infection, or after surgery. Other risk factors for delirium are altered sleep/wake cycle, and absence of daylight. While delirium is very common in critical care, it's difficult to recognise and the reasons why it happens are not fully understood. There are no treatments for delirium. Management focusses on reducing the impact of things that make it more likely for someone to develop delirium. For example, by making sure pain is well controlled and that family members can visit. While it comes with its challenges, maintaining a normal day and night cycle by turning lights off and reducing the number of interruptions during nighttime hours is also a strategy used and research has shown that sometimes this works. Unfortunately, the findings are not the same in every study, and the reasons why these interventions work to reduce delirium are not explored. This study, called DELIGHT-P, wants to look at the relationship between delirium and light exposure to help to understand why absence of daylight is a risk factor for delirium. We think it has something to do with changes in the 'body clock' of patients in critical care. To find this out we will collect blood samples, measure light levels at the bedside, and assess participants for delirium. After discharge from critical care we will see participants again and ask them about their memory and do some thinking tests. We will also do another blood test. The blood samples will be tested for markers of changes to the 'body clock' and others will be tested for proteins that might be useful for recognising when someone has delirium. As this is a pilot study, the research will be done with fewer people taking part. This is to check that the things we want to measure are the right things, and that it's possible to do the research. We hope that in the future we can do a larger study to be able to draw conclusions about what we find. The findings from this study may help us understand how light exposure and an altered body clock contributes to developing delirium. By checking for proteins that might be present in patients who have delirium, it might help us understand what processes are happening in the body to cause delirium. It is possible that through this work, we can identify potential treatment targets for delirium. We hope that by doing this, we may be able to improve some of the memory and thinking problems that people have after a stay in critical care.

Bedside Bike Early Mobilization Program for Inpatients

Hospital immobility leads to serious complications including muscle loss, weakness, delirium, pressure ulcers, and blood clots. Despite being medically stable, hospitalized patients spend over 90% of their time in bed due to staffing shortages, fall risks, and limited physical therapy availability. Within one week of admission, patients can lose approximately 2% of thigh muscle mass per day, and nearly half develop clinically significant hospital-acquired weakness.The Bedside Bike is a portable, low-resistance exercise device that clamps securely to hospital beds, allowing patients to perform leg and arm cycling exercises safely without leaving their bed. This study will evaluate whether hospitalized patients at Indiana University Health facilities can feasibly and safely use the Bedside Bike to maintain mobility during their hospital stay.This quality improvement study will enroll 80 adult inpatients expected to stay at least 3 days. All participants will receive the Bedside Bike in addition to usual care (standard physical therapy and medical treatment). The study will measure how often patients use the device, whether it is safe (tracking any device-related problems), and whether it may help improve outcomes such as hospital length of stay, functional mobility scores, discharge to home, and rates of hospital-acquired weakness. Participants will have functional assessments at admission and discharge, use the Bedside Bike throughout their hospitalization (targeting at least 15 minutes daily), and be followed for 60 days after discharge to track readmissions, falls, living arrangements, and mortality.

Multi-Component Delirium Prevention Bundle in Older Cardiac Intensive Care Unit Patients

The goal of this randomized controlled clinical trial is to learn whether a structured delirium prevention protocol can reduce the occurrence of delirium in older adults admitted to the cardiac intensive care unit (CICU). The study will include participants aged 70 years and older who are hospitalized in the CICU with acute cardiac conditions. The main questions it aims to answer are: Does a structured non-pharmacologic delirium prevention protocol lower the incidence of delirium compared with usual care in older CICU patients? Does this protocol improve short- and long-term clinical outcomes, such as major adverse cardiac events (MACE), functional decline, and cognitive impairment? Researchers will compare participants randomly assigned to receive the delirium prevention protocol (intervention group) with participants receiving usual CICU care (control group) to see if the protocol leads to fewer episodes of delirium and better clinical and functional outcomes. Participants will: Be randomly assigned to the intervention group or the control group. Undergo daily delirium screening using the CAM-ICU tool. Be evaluated by an independent geriatrician who is not the principal investigator, and who will perform all clinical and geriatric assessments external to the treating CICU team. In the intervention group, receive a structured prevention protocol that includes: daily pain assessment using the VAS scale and age-appropriate analgesia as needed, avoiding benzodiazepines when possible, use of earplugs and eye masks at night, early mobilization including bedside cycling exercises, and support for vision and hearing (use of glasses and hearing aids) and family presence overnight. In the control group, receive usual CICU care, including delirium screening with CAM-ICU according to unit practice.

Wearable Sensors for Delirium Detection at an Early Stage (WeSen_delirium)

Delirium is an acute brain-organic syndrome: its clinical manifestation and form are results of a highly complex pathophysiology. Delirium is a serious clinical problem in hospitalized adults. It is the most common neuropsychiatric complication of hospitalization and is associated with high patient burden, increased morbidity and mortality, prolonged length of stay, higher costs, and institutionalization. An early, accurate diagnosis as well as an adequate management are critical to the continued health and functional independence of the affected patients. Prevention strategies contain pharmacological and non-pharmacological interventions. However, their clinical success (effectiveness) is limited and the evidence for the use of pharmacological interventions for the prevention or management of delirium is scarce. The prediction of delirium has become a new promising topic in clinical research. New approaches like the implementation of wearable sensors, in particular wearable accelerometer devices to record movements related to delirium are promising. In this study, the study procedure only includes wearing a consumer-grade sensor on the wrist of the not-dominant hand. This way, vital parameters are measured in order to identify patterns.

PupillOmetry for Prediction of DelirIUM

Delirium in intensive care unit (ICU) is a serious event. It is associated with short-term complications (agitation, self-extubation, accidental removal of catheters, prolonged length of stay and ventilation), excess mortality, functional and cognitive impairment. It is particularly frequent in patients requiring mechanical ventilation but diagnosis is not easy. There are screening scales, but it is insufficiently used in clinical practice: Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) or Intensive Care Delirium Screening Checklist (ICDSC). These scales are time consuming and require trained personnel. Automated pupillometry (AP) is a new device to objectively, rapidly, and reproducibly identify acute brain dysfunction. Recent data suggest that AP could be used to predict delirium in the ICU. This would need to be validated for routine use in the ICU. Evaluate AP parameters on day 3 of invasive mechanical ventilation as a predictive tool for CAM-ICU diagnosed delirium during the first 14 days of ICU stay. Study design: Prospective, multicenter, non-interventional cohort Measurement of the AP parameters at day 3 after ICU admission and their predictive performance for delirium: pupillary diameter, variation of the pupillary diameter, pupillary constriction speed, pupillary dilatation speed, photomotor reflex latency, NPi and symmetry of pupillary responses.

Study of BXCL501 In Agitation Associated With Delirium in ICU Patients

This study is designed to determine and evaluate the optimal BXCL501 starting dose (StartD) that will safely and effectively reduce agitation associated with delirium in ICU patients. This is an ascending adaptive dose study evaluating the safety and efficacy of four potential starting doses of BXCL501 (120 μg, 180 μg, 240 μg, and 300 μg) in reducing agitation levels in adult ICU patients with delirium. For subjects 65 years of age and older, the potential doses will be reduced 50% in line with the Precedex (reference drug) label. The purpose of this clinical trial is to identify an optimally safe and effective BXCL501

Delirium and Cognitive Impairment Development in Hospitalized Older Adults Under Isolation Conditions

The goal of this observational study is to examine if older patients who need to be under isolation precautions due to multidrug resistant bacteria or other reasons have an increased risk of suffering from delirium or cognitive decline compared to older patients without isolation precautions. To compare this, every person under isolation precautions is compared to other persons of the same age, gender, comorbidities, frailty status and hospital department. Delirium is assessed twice daily with a screening tool named 3D-CAM and cognitive performance is tested by the MOCA-Test six weeks after discharge from hospital and compared to baseline values which are assessed directly after study enrollment. The study duration for each patient participating is from the time of enrollment during hospitalization until 6 weeks after hospital discharge.

Intelligent Intensive Care Unit

Delirium, as a common complication of hospitalization, poses significant health problems in hospitalized patients. Though about a third of delirium cases can benefit from intervention, detecting and predicting delirium is still very limited in practice. A common characterization of delirium is change in activity level, causing patients to become hyperactive or hypoactive which is manifested in facial expressions and total body movements. This pilot study is designed to test the feasibility of a delirium detection system using movement data obtained from 3-axis wearable accelerometers and commercially available camera with facial recognition video system in conjunction with electronics medical record (EMR) data to analyze the relation of whole-body movement and facial expressions with delirium.

Predictors of Cognitive Decline and Delirium in Older Women With Ovarian Cancer

Cognitive decline and delirium are common geriatric syndromes that adversely affect treatment adherence, functional independence, quality of life, and survival in older adults with cancer. Women aged 70 years and older with ovarian cancer are particularly vulnerable because of the combined effects of aging, frailty, multimorbidity, and cancer-related factors. However, the prevalence, incidence, determinants, and longitudinal trajectories of cognitive impairment and delirium in this population remain poorly characterized, and validated strategies for risk stratification are lacking. The C.R.O.W.N. (Identification of clinical, functional and biological predictors of Cognitive decline and deliRium in Older Women affected by ovarian caNcer) study is a prospective, single-center, longitudinal observational cohort study designed to identify clinical, functional, and biological predictors of cognitive decline and delirium in older women with ovarian cancer undergoing active treatment. Women aged 70 years or older with newly diagnosed ovarian cancer or first relapse will undergo a comprehensive geriatric assessment before treatment initiation and will be followed for 12 months. Assessments will include standardized cognitive and neuropsychological testing, frailty and functional evaluation, quality-of-life assessment, and systematic delirium screening during hospitalizations. Blood samples will be collected at baseline to measure biomarkers of neurodegeneration and inflammation. Telemonitoring will complement in-person follow-up visits to improve retention and longitudinal assessment. The primary objective is to evaluate the prevalence, incidence, and trajectory of cognitive decline and to identify its clinical, functional, and biological predictors. Secondary objectives include evaluating the occurrence and predictors of delirium, assessing the impact of cognitive disorders on disability, hospitalization, mortality, and quality of life, and developing an integrated risk prediction model combining geriatric assessment and blood-based biomarkers. The study aims to improve early identification of patients at high risk for adverse cognitive outcomes and support personalized oncogeriatric care pathways.