Investigation of Sleep in the Intensive Care Unit

NCT03355053 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: 2017P000090R01NS102190
• Study Type: interventional
• Target: 522
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Delirium; Sleep

Outcome Measures

Primary Outcomes (1)

• 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.

  First 14 hospital days from start of infusion [or until hospital discharge, whichever occurs first]

Secondary Outcomes (4)

• ICU-Delirium-free days (ICU-DFDs)

  First 7 ICU days from start of infusion [or until ICU discharge, whichever occurs first]

• Sleep Quantity-quality (SQ) score

  First 14 ICU days from start of infusion [or until ICU discharge, whichever occurs first]

• Acute Cognitive Function (ACF) score

  First 14 ICU days from start of infusion [or until ICU discharge, whichever occurs first]

• Long-term Cognitive Function (LCF) score

  3-, 6-, and 12 months post-enrollment

Other Outcomes (4)

• Spearman correlation coefficient (rho) between sleep quality and acute cognitive function

  First 14 ICU days from start of infusion [or until ICU discharge, whichever occurs first]

• Average Causal Mediation Effect (ACME) of sleep deprivation on delirium-free days

  First 14 ICU days from start of infusion [or until ICU discharge, whichever occurs first]

• Average Causal Mediation Effect (ACME) of sleep deprivation on acute cognitive outcomes

  First 14 ICU days from start of infusion [or until ICU discharge, whichever occurs first]

Study Arms (3)

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.

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.

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.

Drug: Placebo

Interventions

Dexmedetomidine DRUG

"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."

Also known as: Precedex (dexmedetomidine hydrochloride; Pfizer Inc, NY, Ny)

Dexmedetomidine, continuous low-dose overnight infusion; Dexmedetomidine, continuous very-low-dose overnight infusion

Placebo DRUG

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."

Also known as: Normal saline (0.9% Sodium Chloride; Pfizer Inc, NY, Ny)

Usual care and placebo (normal saline)

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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%)
• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (55)

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MeSH Terms

Conditions

Delirium

Interventions

Dexmedetomidine; Saline Solution; Sodium Chloride

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• M. Brandon Westover, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD/PhD

Model Details: Single-center, prospective, phase II, double-blind, placebo-controlled, three-arm, parallel-group, mechanistic, randomized clinical trial

Study Record Dates

• First Submitted: November 22, 2017
• First Posted: November 28, 2017
• Study Start: May 29, 2018
• Primary Completion: April 5, 2022
• Study Completion: March 24, 2023
• Last Updated: October 8, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)