DeliriumPhase 2ICU-SLEEPNCT03355053
Investigation of Sleep in the Intensive Care Unit
A Phase 2 study testing Dexmedetomidine in people with Delirium and Sleep, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
Sleep deprivation is common and often severe in critically ill patients cared for in intensive care units (ICUs) and is hypothesized to be a modifiable risk factor for delirium, which in turn is hypothesized to be a modifiable risk factor for long-term cognitive disability following recovery from critical illness. Read more about this study
- Who is it for?
- Ages 50 years and older
- What is being tested?
- Dexmedetomidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 522 participants
- Where
- 1 siteUnited States
- Study dates
- 29 May 2018to 24 Mar 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Admitted or scheduled to be admitted to an MGH medical or surgical ICU (Blake 7 or 12, or Ellison 4)
- Male or female, aged ≥ 50 years
- Provision of signed and dated informed consent form (by patient or legally authorized representative (LAR))
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Not on mechanical ventilation at the time of enrollment
- Able to be enrolled before 7PM
- For females of reproductive potential: pregnancy test is negative
Who cannot join
- Dementia, as measured by a score of ≥3.3 on the Informant Questionnaire on Cognitive Decline in the Elderly Short Form (IQCODE-SF)
- Unable to be assessed for delirium (e.g. blindness or deafness)
- Follow-up would be difficult (e.g. active substance abuse, homelessness)
- Pregnancy or lactation
- Known pre-existing neurologic disease or injury with focal neurologic or cognitive deficits
- Serious cardiac disease (e.g. sick sinus syndrome without a pacemaker, sinus bradycardia, second- or third-degree AV block, congestive heart failure with ejection fraction <30%)
Show all 15Show fewer
- Severe liver dysfunction (Child-Pugh class C)
- Severe renal dysfunction (receiving dialysis)
- Low likelihood of survival >24 hours
- Low likelihood of staying in ICU overnight
- Known allergic reactions to components of dexmedetomidine
- Patient is receiving or planning to go on dexmedetomidine at the time of enrollment
- Patient is receiving either of the anticholinergic drugs scopolamine or penehyclidine; or alpha-2-agonist clonidine
- Concomitant enrollment in another study protocol that may interfere with data acquisition or reliability of measurements
- Deemed unsuitable for selection by the research team or ICU providers due to any medical, legal, social, language (non-English speaking) or interpersonal issues that would either compromise the study or the routine care of patients
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Sleep deprivation is common and often severe in critically ill patients cared for in intensive care units (ICUs) and is hypothesized to be a modifiable risk factor for delirium, which in turn is hypothesized to be a modifiable risk factor for long-term cognitive disability following recovery from critical illness. Dexmedetomidine (Dex) reduces the incidence of delirium in ICU patients by unknown mechanisms. The Investigation of Sleep in the Intensive Care Unit (ICU-SLEEP) Trial aims to determine whether Dex reduces delirium by improving sleep, whether a low- and/or very-low dose continuous infusion of Dex increases delirium-free days more, and the relationship between sleep deprivation in the ICU to long-term cognitive outcomes.
Read the detailed description
Sleep deprivation is among the most common complaints about the ICU experience. ICU sleep tends to be light and non-restorative (as opposed to deep/restorative sleep), severely fragmented, and distributed throughout the day and night rather than consolidated into nighttime hours. Sleep-deprived patients suffer from sleep debt, a condition of impaired attention and memory, and cognitive slowing. Sleep disturbances in the ICU arise not only from light and noise pollution, but also from drugs that interfere with brain activity involved in restorative sleep. Sleep deprivation has also been suggested as a major modifiable risk factor for acute encephalopathy, also known as delirium. Delirium is an acute state of confusion that affects up to 50% of non-ventilated ICU patients and is one of six leading causes of preventable morbidity and mortality in hospitalized elderly patients. Many patients who survive delirium experience long-term cognitive impairment and loss of independence. Current medications used in the ICU to treat sleep problems (e.g. benzodiazepines, antipsychotics) do not induce natural sleep and do not prevent delirium. In contrast, the investigators have found that the α2-adrenoceptor agonist dexmedetomidine can induce biomimetic sleep, a brain state whose pattern of electroencephalogram (EEG) activity, cerebral blood flow, and functional connectivity approximates restorative sleep. Moreover, a recent large clinical trial in post-surgical patients suggests that low-dose dexmedetomidine given overnight substantially reduces the risk of delirium. It is unknown whether this benefit is linked to improved sleep, or whether patients with better sleep while in the ICU have better long-term cognitive outcomes. The investigator's central hypothesis is that sleep deprivation substantially mediates both the short- and long-term cognitive impairments associated with delirium in critical illness. To test this hypothesis, the ICU-SLEEP trial aims to: 1A) Compare the burden of delirium, as measured by the number of delirium-free days (DFDs), in ICU patients non-ventilated at study enrollment, who are receiving biomimetic sleep induced by Dex, given as a continuous overnight 1) very-low-dose or 2) low-dose infusion vs. 3) usual care and placebo; 1B) Assess whether the 1) very-low-dose continuous overnight infusion of Dex increases DFDs compared to the 2) low-dose continuous overnight infusion; 2A) Determine whether Dex reduces ICU delirium via reducing sleep deprivation, using causal mediation analysis; 2B) Determine the associations between specific components of acute cognitive impairment, seen in sleep deprivation and delirium, with specific measures of sleep deprivation; 3A) Determine whether ICU patients treated with Dex while in the hospital have a lower incidence of long-term cognitive impairment; 3B) Determine whether any differences in long-term cognitive impairment between ICU survivors treated with Dex vs. usual care and placebo are mediated by differences in sleep deprivation. The knowledge gained will provide insights into the mechanisms by which Dex prevents delirium and guidance on the optimal dosing strategy for prophylactic Dex, which can be used to design pivotal phase 3 clinical trials.
- Being tested
- Dexmedetomidine, Placebo
- Medical subject headings
- Delirium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
Also called Precedex (dexmedetomidine hydrochloride; Pfizer Inc, NY, Ny)
"Dex (Precedex, Dexmedetomidine HCl Injection) is produced by Pfizer Inc, NY, Ny (formerly Hospira). Dex is a white or almost white powder that is freely soluble in water and has a pKa of 7.1. Its partition coefficient in-octanol: water at pH 7.4 is 2.89. Dex is supplied as a clear, colorless, isotonic solution with a pH of 4.5 to 7.0. Each mL contains 118 mcg of dexmedetomidine hydrochloride equivalent to 100 mcg (0.1mg) of dexmedetomidine and 9 mg of sodium chloride in water. The solution is preservative-free and contains no additives or chemical stabilizers. The MGH Pharmacy currently obtains Dex from the supplier as a solution in 50 mL clear-glass bottles, as a clear liquid, at a concentration of 4mcg/mL."
PlaceboDrug
Also called Normal saline (0.9% Sodium Chloride; Pfizer Inc, NY, Ny)
From the package insert: "0.9% Sodium Chloride Injection, USP is sterile and nonpyrogenic. It is produced by Pfizer Inc, NY, Ny (formerly Hospira). It is a parenteral solution containing sodium chloride in water for injection intended for intravenous administration. Each 100 mL of 0.9% Sodium Chloride Injection, USP contains 900 mg sodium chloride in water for injection. Electrolytes per 1000 mL: sodium (Na+ ) 154 mEq; chloride (Cl- ) 154 mEq. The osmolarity is 308 mOsmol/L (calc.). The pH is 5.6 (4.5 to 7.0). This solution contains no bacteriostat, antimicrobial agent or added buffer and is intended only as a single-dose injection. When smaller doses are required, the unused portion should be discarded. 0.9% Sodium Chloride Injection, USP is a parenteral fluid and electrolyte replenisher. Sodium Chloride, USP is chemically designated NaCl, a white crystalline powder freely soluble in water. Water for Injection, USP is chemically designated H2O."
| Study group | Role | What they receive |
|---|---|---|
| Dexmedetomidine, continuous very-low-dose overnight infusion | Active comparator | Patients randomized to this study arm will receive dexmedetomidine, given as a very-low-dose (0.1 mcg/kg/hour group; rate of 0.075 mL/kg/hour at a concentration of 1.33 mcg/mL) continuous overnight infusion. Study drug will be provided by the MGH research pharmacy as a clear liquid and delivered by the research staff directly to the patient's ICU nurse, in a 60 mL syringe/bag (s). Nursing will then administer the study drug intravenously each night (11 hours; 8PM through 7AM) until either discharge from the ICU or up to 7 consecutive nights, whichever occurs first. Receives: Drug: Dexmedetomidine |
| Dexmedetomidine, continuous low-dose overnight infusion | Active comparator | Patients randomized to this study arm will receive dexmedetomidine, given as a low-dose (0.3 mcg/kg/hour group; rate of 0.075 mL/kg/hour at a concentration of 4 mcg/mL) continuous overnight infusion. Study drug will be provided by the MGH research pharmacy as a clear liquid and delivered by the research staff directly to the patient's ICU nurse, in a 60 mL syringe/bag (s). Nursing will then administer the study drug intravenously each night (11 hours; 8PM through 7AM) until either discharge from the ICU or up to 7 consecutive nights, whichever occurs first. Receives: Drug: Dexmedetomidine |
| Usual care and placebo (normal saline) | Placebo comparator | Patients randomized to this study arm will receive standard ICU care plus a normal saline placebo, given as a continuous overnight infusion, at a rate of 0.075 mL/kg/hour. Study drug will be provided by the MGH research pharmacy as a clear liquid and delivered by the research staff directly to the patient's ICU nurse, in a 60 mL syringe/bag (s). Nursing will then administer the study drug intravenously each night (11 hours; 8PM through 7AM) until either discharge from the ICU or up to 7 consecutive nights, whichever occurs first. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
In-hospital Delirium-free days (IH-DFDs)
In-hospital Delirium-free days (IH-DFDs) are calculated as the sum of days without delirium during the first 14 hospital days from start of infusion in the two Dex treatment arms combined (arms 1 and 2) vs. usual care (arm 3). Delirium is defined as any positive Confusion Assessment Method (CAM) or CAM for the ICU (CAM-ICU) assessment, with each yielding a binary result (1 = delirious/CAM+, 0 = non-delirious/CAM-). For each patient, delirium is assessed twice daily. If a patient has any positive delirium assessments on any given day of the assessment days, they are considered to have had delirium during these days. Days with coma are counted together with delirium.
Measured: First 14 hospital days from start of infusion [or until hospital discharge, whichever occurs first]
Secondary outcomes (4)
ICU-Delirium-free days (ICU-DFDs)
ICU-Delirium-free days (ICU-DFDs) are calculated as the sum of days without delirium during the first 7 ICU days from start of infusion in the two Dex treatment arms combined (arms 1 and 2) vs. usual care (arm 3). Delirium is defined as any positive Confusion Assessment Method (CAM) or CAM for the ICU (CAM-ICU) assessment, with each yielding a binary result (1 = delirious/CAM+, 0 = non-delirious/CAM-). For each patient, delirium is assessed twice daily. If a patient has any positive delirium assessments on any given day of the assessment days, they are considered to have had delirium during these days. Days with coma are counted together with delirium.
Measured: First 7 ICU days from start of infusion [or until ICU discharge, whichever occurs first]
Sleep Quantity-quality (SQ) score
The Sleep Quantity-quality (SQ) score is a sleep composite measure formed by averaging the z-scores for raw measures of sleep quality (total sleep time (TST), sleep fragmentation index (SFI), time in N2, time in N3), where a higher SQ score indicates better outcomes.
Measured: First 14 ICU days from start of infusion [or until ICU discharge, whichever occurs first]
Acute Cognitive Function (ACF) score
The Acute Cognitive Function (ACF) score is a reliable change index controlling for practice effects (RCI+PE) for a composite of acute cognitive measures. These include twice daily Confusion Assessment Method-Severity (CAM-S; Short Form (0-7) \& Long Form (0-19), where higher scores indicate increased severity of delirium symptoms); and Psychomotor Vigilance Test (PVT) scores collected in the first 7 ICU days from start of infusion [or until ICU discharge, whichever occurs first]. Composites will be formed by averaging z-scores for CAM-S and PVT scores, where a higher ACF score indicates better outcomes.
Measured: First 14 ICU days from start of infusion [or until ICU discharge, whichever occurs first]
Long-term Cognitive Function (LCF) score
The Long-term Cognitive Function (LCF) score is a composite average of z-scores from long-term cognitive outcome measures of the different components, where a higher LCF score indicates better outcomes.
Measured: 3-, 6-, and 12 months post-enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2017
- Study start29 May 2018
- Primary completion5 Apr 2022
- Study completion24 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (55)Papers the sponsor has linked to this study.
- Other trials for DeliriumStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Single-center, prospective, phase II, double-blind, placebo-controlled, three-arm, parallel-group, mechanistic, randomized clinical trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 522 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael Brandon Westover, Massachusetts General Hospital
- Investigators
- M. Brandon Westover, MD, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03355053
- Sponsor's protocol ID
- 2017P000090
- Other IDs
- R01NS102190
- Acronym
- ICU-SLEEP
- Status last verified
- Oct 2024
- First submitted
- 22 Nov 2017
- Last updated
- 8 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hardin KA, Seyal M, Stewart T, Bonekat HW. Sleep in critically ill chemically paralyzed patients requiring mechanical ventilation. Chest. 2006 Jun;129(6):1468-77. doi: 10.1378/chest.129.6.1468.
PubMed 16778263Fanfulla F, Ceriana P, D'Artavilla Lupo N, Trentin R, Frigerio F, Nava S. Sleep disturbances in patients admitted to a step-down unit after ICU discharge: the role of mechanical ventilation. Sleep. 2011 Mar 1;34(3):355-62. doi: 10.1093/sleep/34.3.355.
PubMed 21358853Gabor JY, Cooper AB, Hanly PJ. Sleep disruption in the intensive care unit. Curr Opin Crit Care. 2001 Feb;7(1):21-7. doi: 10.1097/00075198-200102000-00004.
PubMed 11373507Mundigler G, Delle-Karth G, Koreny M, Zehetgruber M, Steindl-Munda P, Marktl W, Ferti L, Siostrzonek P. Impaired circadian rhythm of melatonin secretion in sedated critically ill patients with severe sepsis. Crit Care Med. 2002 Mar;30(3):536-40. doi: 10.1097/00003246-200203000-00007.
PubMed 11990911Trompeo AC, Vidi Y, Locane MD, Braghiroli A, Mascia L, Bosma K, Ranieri VM. Sleep disturbances in the critically ill patients: role of delirium and sedative agents. Minerva Anestesiol. 2011 Jun;77(6):604-12.
PubMed 21617624Parthasarathy S, Tobin MJ. Effect of ventilator mode on sleep quality in critically ill patients. Am J Respir Crit Care Med. 2002 Dec 1;166(11):1423-9. doi: 10.1164/rccm.200209-999OC. Epub 2002 Sep 5.
PubMed 12406837Wilson JE, Mart MF, Cunningham C, Shehabi Y, Girard TD, MacLullich AMJ, Slooter AJC, Ely EW. Delirium. Nat Rev Dis Primers. 2020 Nov 12;6(1):90. doi: 10.1038/s41572-020-00223-4.
PubMed 33184265Pandharipande 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.
PubMed 24088092Mart 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.
PubMed 32746469Leslie DL, Marcantonio ER, Zhang Y, Leo-Summers L, Inouye SK. One-year health care costs associated with delirium in the elderly population. Arch Intern Med. 2008 Jan 14;168(1):27-32. doi: 10.1001/archinternmed.2007.4.
PubMed 18195192Vasilevskis EE, Chandrasekhar R, Holtze CH, Graves J, Speroff T, Girard TD, Patel MB, Hughes CG, Cao A, Pandharipande PP, Ely EW. The Cost of ICU Delirium and Coma in the Intensive Care Unit Patient. Med Care. 2018 Oct;56(10):890-897. doi: 10.1097/MLR.0000000000000975.
PubMed 30179988Diekelmann S, Born J. The memory function of sleep. Nat Rev Neurosci. 2010 Feb;11(2):114-26. doi: 10.1038/nrn2762. Epub 2010 Jan 4.
PubMed 20046194Ngo HV, Martinetz T, Born J, Molle M. Auditory closed-loop stimulation of the sleep slow oscillation enhances memory. Neuron. 2013 May 8;78(3):545-53. doi: 10.1016/j.neuron.2013.03.006. Epub 2013 Apr 11.
PubMed 23583623Staresina BP, Bergmann TO, Bonnefond M, van der Meij R, Jensen O, Deuker L, Elger CE, Axmacher N, Fell J. Hierarchical nesting of slow oscillations, spindles and ripples in the human hippocampus during sleep. Nat Neurosci. 2015 Nov;18(11):1679-1686. doi: 10.1038/nn.4119. Epub 2015 Sep 21.
PubMed 26389842Nedergaard M. Neuroscience. Garbage truck of the brain. Science. 2013 Jun 28;340(6140):1529-30. doi: 10.1126/science.1240514.
PubMed 23812703
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of Sleep in the Intensive Care Unit
- ClinicalTrials.gov ID
- NCT03355053
- Acronym / sponsor ID
- ICU-SLEEP / 2017P000090
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 522 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 29 May 2018 (actual)
- Primary completion
- 5 Apr 2022 (actual)
- Study completion
- 24 Mar 2023 (actual)
- First posted
- 28 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Sleep deprivation is common and often severe in critically ill patients cared for in intensive care units (ICUs) and is hypothesized to be a modifiable risk factor for delirium, which in turn is hypothesized to be a modifiable risk factor for long-term cognitive disability following recovery from critical illness. Dexmedetomidine (Dex) reduces the incidence of delirium in ICU patients by unknown mechanisms. The Investigation of Sleep in the Intensive Care Unit (ICU-SLEEP) Trial aims to determine whether Dex reduces delirium by improving sleep, whether a low- and/or very-low dose continuous infusion of Dex increases delirium-free days more, and the relationship between sleep deprivation in the ICU to long-term cognitive outcomes.
Detailed description
Sleep deprivation is among the most common complaints about the ICU experience. ICU sleep tends to be light and non-restorative (as opposed to deep/restorative sleep), severely fragmented, and distributed throughout the day and night rather than consolidated into nighttime hours. Sleep-deprived patients suffer from sleep debt, a condition of impaired attention and memory, and cognitive slowing. Sleep disturbances in the ICU arise not only from light and noise pollution, but also from drugs that interfere with brain activity involved in restorative sleep. Sleep deprivation has also been suggested as a major modifiable risk factor for acute encephalopathy, also known as delirium. Delirium is an acute state of confusion that affects up to 50% of non-ventilated ICU patients and is one of six leading causes of preventable morbidity and mortality in hospitalized elderly patients. Many patients who survive delirium experience long-term cognitive impairment and loss of independence. Current medications used in the ICU to treat sleep problems (e.g. benzodiazepines, antipsychotics) do not induce natural sleep and do not prevent delirium. In contrast, the investigators have found that the α2-adrenoceptor agonist dexmedetomidine can induce biomimetic sleep, a brain state whose pattern of electroencephalogram (EEG) activity, cerebral blood flow, and functional connectivity approximates restorative sleep. Moreover, a recent large clinical trial in post-surgical patients suggests that low-dose dexmedetomidine given overnight substantially reduces the risk of delirium. It is unknown whether this benefit is linked to improved sleep, or whether patients with better sleep while in the ICU have better long-term cognitive outcomes. The investigator's central hypothesis is that sleep deprivation substantially mediates both the short- and long-term cognitive impairments associated with delirium in critical illness. To test this hypothesis, the ICU-SLEEP trial aims to: 1A) Compare the burden of delirium, as measured by the number of delirium-free days (DFDs), in ICU patients non-ventilated at study enrollment, who are receiving biomimetic sleep induced by Dex, given as a continuous overnight 1) very-low-dose or 2) low-dose infusion vs. 3) usual care and placebo; 1B) Assess whether the 1) very-low-dose continuous overnight infusion of Dex increases DFDs compared to the 2) low-dose continuous overnight infusion; 2A) Determine whether Dex reduces ICU delirium via reducing sleep deprivation, using causal mediation analysis; 2B) Determine the associations between specific components of acute cognitive impairment, seen in sleep deprivation and delirium, with specific measures of sleep deprivation; 3A) Determine whether ICU patients treated with Dex while in the hospital have a lower incidence of long-term cognitive impairment; 3B) Determine whether any differences in long-term cognitive impairment between ICU survivors treated with Dex vs. usual care and placebo are mediated by differences in sleep deprivation. The knowledge gained will provide insights into the mechanisms by which Dex prevents delirium and guidance on the optimal dosing strategy for prophylactic Dex, which can be used to design pivotal phase 3 clinical trials.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Single-center, prospective, phase II, double-blind, placebo-controlled, three-arm, parallel-group, mechanistic, randomized clinical trial
| Arm | Type | Receives |
|---|---|---|
| Dexmedetomidine, continuous very-low-dose overnight infusion | Active comparator | Drug: DexmedetomidinePatients randomized to this study arm will receive dexmedetomidine, given as a very-low-dose (0.1 mcg/kg/hour group; rate of 0.075 mL/kg/hour at a concentration of 1.33 mcg/mL) continuous overnight infusion. Study drug will be provided by the MGH research pharmacy as a clear liquid and delivered by the research staff directly to the patient's ICU nurse, in a 60 mL syringe/bag (s). Nursing will then administer the study drug intravenously each night (11 hours; 8PM through 7AM) until either discharge from the ICU or up to 7 consecutive nights, whichever occurs first. |
| Dexmedetomidine, continuous low-dose overnight infusion | Active comparator | Drug: DexmedetomidinePatients randomized to this study arm will receive dexmedetomidine, given as a low-dose (0.3 mcg/kg/hour group; rate of 0.075 mL/kg/hour at a concentration of 4 mcg/mL) continuous overnight infusion. Study drug will be provided by the MGH research pharmacy as a clear liquid and delivered by the research staff directly to the patient's ICU nurse, in a 60 mL syringe/bag (s). Nursing will then administer the study drug intravenously each night (11 hours; 8PM through 7AM) until either discharge from the ICU or up to 7 consecutive nights, whichever occurs first. |
| Usual care and placebo (normal saline) | Placebo comparator | Drug: PlaceboPatients randomized to this study arm will receive standard ICU care plus a normal saline placebo, given as a continuous overnight infusion, at a rate of 0.075 mL/kg/hour. Study drug will be provided by the MGH research pharmacy as a clear liquid and delivered by the research staff directly to the patient's ICU nurse, in a 60 mL syringe/bag (s). Nursing will then administer the study drug intravenously each night (11 hours; 8PM through 7AM) until either discharge from the ICU or up to 7 consecutive nights, whichever occurs first. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Admitted or scheduled to be admitted to an MGH medical or surgical ICU (Blake 7 or 12, or Ellison 4)
- Male or female, aged ≥ 50 years
- Provision of signed and dated informed consent form (by patient or legally authorized representative (LAR))
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Not on mechanical ventilation at the time of enrollment
Key exclusion criteria (15 listed)
- Dementia, as measured by a score of ≥3.3 on the Informant Questionnaire on Cognitive Decline in the Elderly Short Form (IQCODE-SF)
- Unable to be assessed for delirium (e.g. blindness or deafness)
- Follow-up would be difficult (e.g. active substance abuse, homelessness)
- Pregnancy or lactation
- Known pre-existing neurologic disease or injury with focal neurologic or cognitive deficits
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexmedetomidineAlso: Precedex (dexmedetomidine hydrochloride; Pfizer Inc, NY, Ny)"Dex (Precedex, Dexmedetomidine HCl Injection) is produced by Pfizer Inc, NY, Ny (formerly Hospira). Dex is a white or almost white powder that is freely soluble in water and has a pKa of 7.1. Its partition coefficient in-octanol: water at pH 7.4 is 2.89. Dex is supplied as a clear, colorless, isotonic solution with a pH of 4.5 to 7.0. Each mL contains 118 mcg of dexmedetomidine hydrochloride equivalent to 100 mcg (0.1mg) of dexmedetomidine and 9 mg of sodium chloride in water. The solution is preservative-free and contains no additives or chemical stabilizers. The MGH Pharmacy currently obtains Dex from the supplier as a solution in 50 mL clear-glass bottles, as a clear liquid, at a concentration of 4mcg/mL." | Drug | Dexmedetomidine, continuous low-dose overnight infusion, Dexmedetomidine, continuous very-low-dose overnight infusion |
| PlaceboAlso: Normal saline (0.9% Sodium Chloride; Pfizer Inc, NY, Ny)From the package insert: "0.9% Sodium Chloride Injection, USP is sterile and nonpyrogenic. It is produced by Pfizer Inc, NY, Ny (formerly Hospira). It is a parenteral solution containing sodium chloride in water for injection intended for intravenous administration. Each 100 mL of 0.9% Sodium Chloride Injection, USP contains 900 mg sodium chloride in water for injection. Electrolytes per 1000 mL: sodium (Na+ ) 154 mEq; chloride (Cl- ) 154 mEq. The osmolarity is 308 mOsmol/L (calc.). The pH is 5.6 (4.5 to 7.0). This solution contains no bacteriostat, antimicrobial agent or added buffer and is intended only as a single-dose injection. When smaller doses are required, the unused portion should be discarded. 0.9% Sodium Chloride Injection, USP is a parenteral fluid and electrolyte replenisher. Sodium Chloride, USP is chemically designated NaCl, a white crystalline powder freely soluble in water. Water for Injection, USP is chemically designated H2O." | Drug | Usual care and placebo (normal saline) |
Primary outcome
In-hospital Delirium-free days (IH-DFDs)
Time frame: First 14 hospital days from start of infusion [or until hospital discharge, whichever occurs first]
In-hospital Delirium-free days (IH-DFDs) are calculated as the sum of days without delirium during the first 14 hospital days from start of infusion in the two Dex treatment arms combined (arms 1 and 2) vs. usual care (arm 3). Delirium is defined as any positive Confusion Assessment Method (CAM) or CAM for the ICU (CAM-ICU) assessment, with each yielding a binary result (1 = delirious/CAM+, 0 = non-delirious/CAM-). For each patient, delirium is assessed twice daily. If a patient has any positive delirium assessments on any given day of the assessment days, they are considered to have had delirium during these days. Days with coma are counted together with delirium.
4 secondary outcomes
ICU-Delirium-free days (ICU-DFDs)
Time frame: First 7 ICU days from start of infusion [or until ICU discharge, whichever occurs first]
Sleep Quantity-quality (SQ) score
Time frame: First 14 ICU days from start of infusion [or until ICU discharge, whichever occurs first]
Acute Cognitive Function (ACF) score
Time frame: First 14 ICU days from start of infusion [or until ICU discharge, whichever occurs first]
Long-term Cognitive Function (LCF) score
Time frame: 3-, 6-, and 12 months post-enrollment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2024.
- Background: PubMed 16778263Hardin KA, Seyal M, Stewart T, Bonekat HW. Sleep in critically ill chemically paralyzed patients requiring mechanical ventilation. Chest. 2006 Jun;129(6):1468-77. doi: 10.1378/chest.129.6.1468.
- Background: PubMed 21358853Fanfulla F, Ceriana P, D'Artavilla Lupo N, Trentin R, Frigerio F, Nava S. Sleep disturbances in patients admitted to a step-down unit after ICU discharge: the role of mechanical ventilation. Sleep. 2011 Mar 1;34(3):355-62. doi: 10.1093/sleep/34.3.355.
- Background: PubMed 11373507Gabor JY, Cooper AB, Hanly PJ. Sleep disruption in the intensive care unit. Curr Opin Crit Care. 2001 Feb;7(1):21-7. doi: 10.1097/00075198-200102000-00004.
- Background: PubMed 11990911Mundigler G, Delle-Karth G, Koreny M, Zehetgruber M, Steindl-Munda P, Marktl W, Ferti L, Siostrzonek P. Impaired circadian rhythm of melatonin secretion in sedated critically ill patients with severe sepsis. Crit Care Med. 2002 Mar;30(3):536-40. doi: 10.1097/00003246-200203000-00007.
- Background: PubMed 21617624Trompeo AC, Vidi Y, Locane MD, Braghiroli A, Mascia L, Bosma K, Ranieri VM. Sleep disturbances in the critically ill patients: role of delirium and sedative agents. Minerva Anestesiol. 2011 Jun;77(6):604-12.
- Background: PubMed 12406837Parthasarathy S, Tobin MJ. Effect of ventilator mode on sleep quality in critically ill patients. Am J Respir Crit Care Med. 2002 Dec 1;166(11):1423-9. doi: 10.1164/rccm.200209-999OC. Epub 2002 Sep 5.
- Background: PubMed 33184265Wilson JE, Mart MF, Cunningham C, Shehabi Y, Girard TD, MacLullich AMJ, Slooter AJC, Ely EW. Delirium. Nat Rev Dis Primers. 2020 Nov 12;6(1):90. doi: 10.1038/s41572-020-00223-4.
- Background: PubMed 24088092Pandharipande 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.
- Background: PubMed 32746469Mart 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.
- Background: PubMed 18195192Leslie DL, Marcantonio ER, Zhang Y, Leo-Summers L, Inouye SK. One-year health care costs associated with delirium in the elderly population. Arch Intern Med. 2008 Jan 14;168(1):27-32. doi: 10.1001/archinternmed.2007.4.
- Background: PubMed 30179988Vasilevskis EE, Chandrasekhar R, Holtze CH, Graves J, Speroff T, Girard TD, Patel MB, Hughes CG, Cao A, Pandharipande PP, Ely EW. The Cost of ICU Delirium and Coma in the Intensive Care Unit Patient. Med Care. 2018 Oct;56(10):890-897. doi: 10.1097/MLR.0000000000000975.
- Background: PubMed 20046194Diekelmann S, Born J. The memory function of sleep. Nat Rev Neurosci. 2010 Feb;11(2):114-26. doi: 10.1038/nrn2762. Epub 2010 Jan 4.
- Airgo™ \[Internet\]. Airgo™. \[cited 2022 Jul 8\]. Available from: https://www.myairgo.comLink provided by the sponsor.
- Merino S, Atzmueller M. Behavioral Topic Modeling on Naturalistic Driving Data. 2018; Available from: https://researchbuddies.com/wp-content/uploads/2020/05/Behavioral\_Topic\_Modeling\_on\_Naturalistic\_Driving\_Data.pdfLink provided by the sponsor.
- Heller LJ, Skinner CS, Tomiyama AJ, Epel ES, Hall PA, Allan J, et al. Trail-Making Test. In: Gellman MD, Turner JR, editors. Encyclopedia of Behavioral Medicine \[Internet\]. New York, NY: Springer New York; 2013 \[cited 2022 Jul 8\]. p. 1986-7.Link provided by the sponsor.
- Brandt J, Spencer M, Folstein M. The Telephone Interview for Cognitive Status. Neuropsychiatry, Neuropsychology and Behavioral Neurology. 1988 Jan 1;1(2):111-7.Link provided by the sponsor.
- Fish J. Rankin Scale. In: Kreutzer JS, DeLuca J, Caplan B, editors. Encyclopedia of Clinical Neuropsychology \[Internet\]. New York, NY: Springer New York; 2011 \[cited 2022 Jul 8\]. p. 2110-2.Link provided by the sponsor.
- Computing Comorbidity Scores (Charlson Comorbidity Index)Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
M. Brandon Westover, MD, PhD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dexmedetomidine in people with Delirium and Sleep, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
In-hospital Delirium-free days (IH-DFDs) (time frame: First 14 hospital days from start of infusion [or until hospital discharge, whichever occurs first]). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03355053, which also lists 55 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2024.