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

• Sponsor: University of California, San Diego (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02691013
• Collaborator: (none)
• Enrollment: 120
• Arms: 2
• Anticipated Duration (Months): 82

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Delirium; Sleep Deprivation	Drug: Ramelteon; Drug: Placebo	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: The Impact of Ramelteon on Sleep and Delirium in Patients Who Undergo Pulmonary Thromboendarterectomy (PTE) Surgery
• Actual Study Start Date: Feb 1, 2016
• Actual Primary Completion Date: Dec 31, 2017
• Anticipated Study Completion Date: Dec 1, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Duration of Delirium [Twice daily for up to 10 days]

   Measured twice daily during the ICU stay using the Confusions Assessment Method instrument.

2. Total Duration of Sleep [Daily for up to 10 days]

   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.

Secondary Outcome Measures

1. Number of Participants With Delirium [Twice daily for up to 10 days]

   Measured twice daily over the course of the ICU stay using the Confusion Assessment Method instrument

2. Average Daily Critical Care Pain Observation Tool (CPOT) [10 days]

   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.

3. Length of Hospital Stay [Duration of hospital admission]

4. Length of ICU Stay [Duration of hospital admission]

5. Measures of Light Quality in the Patient's Room [3 days]

   Light meter placed at bedside in patient room; this meter measured and recorded the light level in lux for ever minutes.

6. Measures of the Sound Levels in the Patient's Room [3 days]

   Sound meter was placed at bedside in each patient room. This meter measured and recorded the sound level in decibels every two seconds.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• University of California, San Diego

Investigators

• Principal Investigator: Robert Owens, 8686577118

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 23, 2015

More Information

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. Review.
• 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.

• Responsible Party: Robert L. Owens, Associate Professor, Pulmonary, Critical Care and Sleep Medicine, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT02691013
• Other Study ID Numbers: 151294
• First Posted: Feb 24, 2016
• Last Update Posted: Feb 8, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Delirium; Sleep Deprivation

Study Results

Participant Flow

Arm/Group Title	Placebo	Ramelteon
Arm/Group Description	Patients will receive a Placebo tablet every evening starting the night prior to the procedure for a maximum of 7 nights total. Placebo	Patients will receive Ramelteon 8mg every evening starting the night prior to the procedure for a maximum of 7 nights total. Ramelteon
Period Title: Overall Study
STARTED	61	59
COMPLETED	58	59
NOT COMPLETED	3	0

Baseline Characteristics

Arm/Group Title	Placebo	Ramelteon	Total
Arm/Group Description	Patients will receive a Placebo tablet every evening. Placebo	Patients will receive Ramelteon 8mg every evening. Ramelteon	Total of all reporting groups
Overall Participants	58	59	117
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	39 67.2%	39 66.1%	78 66.7%
>=65 years	19 32.8%	20 33.9%	39 33.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.1 (15.8)	58.1 (14.1)	57.1 (14.9)
Sex: Female, Male (Count of Participants)
Female	29 50%	30 50.8%	59 50.4%
Male	29 50%	29 49.2%	58 49.6%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	58 100%	59 100%	117 100%

Outcome Measures

1. Primary Outcome

Title	Duration of Delirium
Description	Measured twice daily during the ICU stay using the Confusions Assessment Method instrument.
Time Frame	Twice daily for up to 10 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Ramelteon
Arm/Group Description	Patients will receive a Placebo tablet every evening starting the night prior to the procedure for a maximum of 7 nights total. Placebo	Patients will receive Ramelteon 8mg every evening starting the night prior to the procedure for a maximum of 7 nights total. Ramelteon
Measure Participants	58	59
Median (Inter-Quartile Range) [hours]	16	24

2. Primary Outcome

Title	Total Duration of Sleep
Description	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.
Time Frame	Daily for up to 10 days

Outcome Measure Data

Analysis Population Description

Due to funding & logistical constraints, only a subset of subjects would've been able to do the electroencephalography (EEG) monitoring used for sleep assessment. Thus, Total Duration of Sleep was not measured and we focused on our a priori secondary outcome of incident delirium, a change made before the start of data collection or analysis.

Arm/Group Title	Placebo	Ramelteon
Arm/Group Description	Patients will receive a Placebo tablet every evening. Placebo	Patients will receive Ramelteon 8mg every evening. Ramelteon
Measure Participants	0	0

3. Secondary Outcome

Title	Number of Participants With Delirium
Description	Measured twice daily over the course of the ICU stay using the Confusion Assessment Method instrument
Time Frame	Twice daily for up to 10 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Ramelteon
Arm/Group Description	Patients will receive a Placebo tablet every evening starting the night prior to the procedure for a maximum of 7 nights total. Placebo	Patients will receive Ramelteon 8mg every evening starting the night prior to the procedure for a maximum of 7 nights total. Ramelteon
Measure Participants	58	59
Count of Participants [Participants]	22 37.9%	19 32.2%

4. Secondary Outcome

Title	Average Daily Critical Care Pain Observation Tool (CPOT)
Description	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.
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Length of Hospital Stay
Time Frame	Duration of hospital admission

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Ramelteon
Arm/Group Description	Patients will receive a Placebo tablet every evening starting the night prior to the procedure for a maximum of 7 nights total. Placebo	Patients will receive Ramelteon 8mg every evening starting the night prior to the procedure for a maximum of 7 nights total. Ramelteon
Measure Participants	58	59
Median (Inter-Quartile Range) [days]	12	12

6. Secondary Outcome

Title	Length of ICU Stay
Time Frame	Duration of hospital admission

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Ramelteon
Arm/Group Description	Patients will receive a Placebo tablet every evening starting the night prior to the procedure for a maximum of 7 nights total. Placebo	Patients will receive Ramelteon 8mg every evening starting the night prior to the procedure for a maximum of 7 nights total. Ramelteon
Measure Participants	58	59
Median (Inter-Quartile Range) [days]	4	4

7. Secondary Outcome

Title	Measures of Light Quality in the Patient's Room
Description	Light meter placed at bedside in patient room; this meter measured and recorded the light level in lux for ever minutes.
Time Frame	3 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Measures of the Sound Levels in the Patient's Room
Description	Sound meter was placed at bedside in each patient room. This meter measured and recorded the sound level in decibels every two seconds.
Time Frame	3 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	10 days
Arm/Group Title	Placebo		Ramelteon
Arm/Group Description	Patients will receive a Placebo tablet every evening starting the night prior to the procedure for a maximum of 7 nights total. Placebo		Patients will receive Ramelteon 8mg every evening starting the night prior to the procedure for a maximum of 7 nights total. Ramelteon
All Cause Mortality
	Placebo		Ramelteon
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/61 (6.6%)		3/59 (5.1%)
Serious Adverse Events
	Placebo		Ramelteon
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/61 (0%)		0/59 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Ramelteon
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/61 (0%)		0/59 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.