Eszopiclone and Inflammatory Mediators in Patients With Acute Coronary Syndrome

The purpose of the study is to examine the effects of Eszopiclone, a sleep aid, on inflammatory mediators and coagulability in patients with a recent myocardial infarction.

Study Overview

• Status: Completed
• Conditions: Sleep Disorder; Acute Coronary Syndrome
• Intervention / Treatment: Drug: Eszopiclone; Other: Placebo

Detailed Description

Abnormalities of sleep are common in hospitalized patients, but the mechanisms and consequences are not well understood. In many of these patients, sleep is very disrupted, occurs during the daytime, and circadian rhythm is diminished or lost. Hospitalized patients experience more frequent arousals and awakenings than is normal and show decreases in rapid eye movement and slow wave sleep. The degree of sleep fragmentation is at least equivalent to that seen in patients with obstructive sleep apnea. About 20% of arousals and awakenings are related to noise, 10% are related to health care personnel and care-related activities, and the cause for the remainder is not known, although severity of underlying disease is likely an important factor.

In studies of sleep following acute myocardial infarction, marked disturbances have been found in patients, whether in the ICU and on the wards. These disturbances include long periods of wakefulness; poor sleep efficiency, and disruption of REM sleep. The fact that there is also a loss in circadian rhythm in these patients may indicate a widespread disruption of bodily homeostasis which, in turn, may be related to the infarct itself, to a more generalized physiological response to stress or to other factors. Sleep disruption can induce sympathetic activation and elevation of blood pressure, which may contribute to patient morbidity.

It has been shown that there is an increased level of some inflammatory and coagulation factors in the recovery period following an acute myocardial infarction (MI). Post MI patients have higher levels of TNF-α, IL-6 and tissue plasminogen activator as well as lower levels of antithrombin III and protein C.

The aim of this study is to determine whether the sleep-aid Eszopiclone can improve sleep, decrease inflammation, and decrease pro-coagulation factors in patients who have recently suffered myocardial infarction when compared with a control group without sleep aids. Eszopiclone is a benzodiazepine receptor agonist which improves sleep quality by reducing the time to sleep onset and reduces wakefulness during the sleep period. Unlike benzodiazepines, it does not affect the deeper stage 3 and 4 sleep. The result is that it provides a more nearly normal night sleep than other sleep aids. It is hoped that improved sleep patterns will result in more rapid normalization of inflammatory and coagulation factors and perhaps more rapid recovery.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85723
      • Southern Arizona VA Health Care System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with recent (less than or equal to 8 weeks) "uncomplicated" acute myocardial infarction, can either be ST elevation MI (STEMI) or non-ST elevation MI (non-STEMI) and subsequent to successful treatment (percutaneous revascularization or medical therapy).

Exclusion Criteria:

• Obstructive sleep apnea (OSA, defined as apnea-hypopnea index > 15 per hour) or previous diagnosis of OSA.
• Patients with life-threatening arrhythmias (such as atrial fibrillation/flutter with hypotension, ventricular tachycardia, or ventricular fibrillation, or significant heart block that requires pacing [Type III, Type IIb]), cardiogenic shock, severe heart failure requiring high levels of inspired oxygen (FiO2 >40%), persistent chest pain despite medical or other interventions, and patients who are considered too unstable to participate for other medical reasons or complications (such as concomitant strokes, retroperitoneal hematoma, gastro-intestinal bleeding). Also excluded are patients with history of cardiac arrest during the same hospitalization.
• Unable to take oral medications
• Use of other sedative-hypnotics
• Hypersensitivity to Eszopiclone or any component of the formulation
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1: Eszopiclone; Subjects receive Eszopiclone for three consecutive nights to observe changes in sleep measures, and inflammatory and coagulation factors	Drug: Eszopiclone; Subject receives Eszopiclone for 3 consecutive nights. 3 mg orally at bedtime for patients age 64 and under, and 2 mg QHS for patients age 65 and older.; Other Names: Lunesta
Placebo Comparator: 2: Placebo; Subjects given placebo for 3 consecutive nights to observe changes in sleep measures, and inflammatory and coagulation factors	Other: Placebo; Subjects are given placebo for 3 consecutive nights

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Circulating Inflammatory Cytokines (Interleukin [IL]-1B, IL-6, IL-10, and Tumor Necrosis Alpha [TNF-α]) and Pro-coagulant Mediators (Soluble P-selectin and CD40 Ligand).	Not performed. Zero subjects were randomized. Many potential participants screen-failed.	2 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in Objective and Subjective Measures of Sleep	4 days

Collaborators and Investigators

• Sponsor: University of Arizona
• Collaborators: Sunovion; Southern Arizona VA Health Care System
• Investigators: Principal Investigator: Sairam Parthasarathy, MD, Southern Arizona VA Health Care System

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: January 12, 2009
• First Submitted That Met QC Criteria: January 13, 2009
• First Posted (Estimate): January 14, 2009

Study Record Updates

• Last Update Posted (Estimate): December 20, 2016
• Last Update Submitted That Met QC Criteria: October 26, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Acute Coronary Syndrome; cytokines; pro-coagulant mediators; sleep disorders
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Neurologic Manifestations; Disease; Syndrome; Sleep Wake Disorders; Parasomnias; Acute Coronary Syndrome; Physiological Effects of Drugs; Central Nervous System Depressants; Hypnotics and Sedatives; Eszopiclone
• Other Study ID Numbers: HSC# 07-0797-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No