The Impact of Ramelteon on Sleep and Delirium in Patients Who Undergo Pulmonary Thromboendarterectomy (PTE) Surgery

Sleep deprivation is known to affect brain function but is often ignored in the sickest patients including those in the intensive care unit after major surgery. In these patients, the levels of melatonin can also be altered. Melatonin is a hormone secreted in the brain that maintains the body's sleep-wake, or circadian, cycle. The investigators want to test whether improving sleep quality affects the risk of developing confusion (delirium) in patients having clot removed from their lung (open heart surgery). In order to improve sleep quality, the investigators will conduct a study of Ramelteon, a medication that mimics the activity of melatonin and measure its effects on levels of melatonin and monitor sleep.

Study Overview

• Status: Active, not recruiting
• Conditions: Delirium; Sleep Deprivation
• Intervention / Treatment: Drug: Placebo; Drug: Ramelteon

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with Chronic Thromboembolic Pulmonary Hypertension (CTEPH) who are admitted to UCSD for a planned PTE surgery.
• Age > 18 years

Exclusion Criteria:

• Pregnancy
• Cirrhosis of any etiology
• Current use of any atypical antipsychotic including Fluvoxamine (contra-indicated with Ramelteon)
• Any contraindication to EEG/Sleep recording
• Non-English speaking (who are unable to complete delirium questionnaires)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Patients will receive a Placebo tablet every evening.	Drug: Placebo
ACTIVE_COMPARATOR: Ramelteon; Patients will receive Ramelteon 8mg every evening.	Drug: Ramelteon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Delirium	Measured twice daily during the ICU stay using the Confusions Assessment Method instrument.	Twice daily for up to 10 days
Total Duration of Sleep	Participants wore an actigraphy device on their wrist for the duration of their ICU stay. This device continuously measures activity, and thus estimates sleep time.	Daily for up to 10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Delirium	Measured twice daily over the course of the ICU stay using the Confusion Assessment Method instrument	Twice daily for up to 10 days
Average Daily Critical Care Pain Observation Tool (CPOT)	average daily pain level using the CPOT Participants can score from 0 to 6 on the CPOT scale, with 0 being no pain (calm, comfortable), and 6 representing significant pain/agitation.	10 days
Length of Hospital Stay		Duration of hospital admission
Length of ICU Stay		Duration of hospital admission
Measures of Light Quality in the Patient's Room	Light meter placed at bedside in patient room; this meter measured and recorded the light level in lux for ever minutes.	3 days
Measures of the Sound Levels in the Patient's Room	Sound meter was placed at bedside in each patient room. This meter measured and recorded the sound level in decibels every two seconds.	3 days

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Investigators: Principal Investigator: Robert Owens, 8686577118

Publications and helpful links

General Publications

• Al-Aama T, Brymer C, Gutmanis I, Woolmore-Goodwin SM, Esbaugh J, Dasgupta M. Melatonin decreases delirium in elderly patients: a randomized, placebo-controlled trial. Int J Geriatr Psychiatry. 2011 Jul;26(7):687-94. doi: 10.1002/gps.2582. Epub 2010 Sep 15. Erratum In: Int J Geriatr Psychiatry. 2014 May;29(5):550.
• Bellapart J, Boots R. Potential use of melatonin in sleep and delirium in the critically ill. Br J Anaesth. 2012 Apr;108(4):572-80. doi: 10.1093/bja/aes035.
• Hatta K, Kishi Y, Wada K, Takeuchi T, Odawara T, Usui C, Nakamura H; DELIRIA-J Group. Preventive effects of ramelteon on delirium: a randomized placebo-controlled trial. JAMA Psychiatry. 2014 Apr;71(4):397-403. doi: 10.1001/jamapsychiatry.2013.3320.
• Jaiswal SJ, Vyas AD, Heisel AJ, Ackula H, Aggarwal A, Kim NH, Kerr KM, Madani M, Pretorius V, Auger WR, Fernandes TM, Malhotra A, Owens RL. Ramelteon for Prevention of Postoperative Delirium: A Randomized Controlled Trial in Patients Undergoing Elective Pulmonary Thromboendarterectomy. Crit Care Med. 2019 Dec;47(12):1751-1758. doi: 10.1097/CCM.0000000000004004.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2016
• Primary Completion (ACTUAL): December 31, 2017
• Study Completion (ANTICIPATED): December 1, 2022

Study Registration Dates

• First Submitted: December 28, 2015
• First Submitted That Met QC Criteria: February 23, 2016
• First Posted (ESTIMATE): February 24, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2022
• Last Update Submitted That Met QC Criteria: February 1, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Dyssomnias; Sleep Wake Disorders; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Sleep Deprivation
• Other Study ID Numbers: 151294

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO