PODIUM: Prevention of Delirium in Inpatients Utilizing Melatonin

• Sponsor: Yale University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02654314
• Collaborator: (none)
• Enrollment: 277
• Location: 1
• Arms: 2
• Duration (Months): 16.1
• Patients Per Site Per Month: 17.2

Study Details

Study Description

Brief Summary

A double blind randomized controlled trial investigating melatonin, 5mg, compared to placebo, given to patients at least 65 years old, admitted to the hospital on a general medical floor, to prevent delirium.

Condition or Disease	Intervention/Treatment	Phase
Delirium	Drug: Melatonin; Other: Placebo	Phase 3

Detailed Description

This study will be a randomized double blind controlled trial, designed to evaluate the efficacy of melatonin in decreasing the incidence of delirium in elderly hospitalized adults compared to a placebo capsule. The study will be conducted on 4 general Internal Medicine inpatient floors at Yale-New Haven Hospital, St. Raphael's campus.

Within 24 hours of admission to the floor, study subjects will be approached by a member of the research team, and asked for informed consent. Patients that consent to participate will be randomized to either the treatment or the placebo arm. Each subject will be administered a capsule containing either placebo or 5 mg melatonin each evening at 9 p.m. The capsules will be prepared and administered by the Yale-New haven Hospital Investigational Drug Service. The capsules will be administered nightly until discharge or a maximum of 2 weeks, if the hospitalization is prolonged.

Subjects will be assessed twice daily by the floor nurses for evidence of delirium using the Short CAM (Confusion Assessment Method), which is a validated clinical tool for identifying delirium, and the current standard of practice tool for the diagnosis of delirium.

Study Design

• Study Type: Interventional
• Actual Enrollment: 277 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Prevention of Delirium in Inpatients Utilizing Melatonin
• Study Start Date: Jul 1, 2016
• Actual Primary Completion Date: Nov 3, 2017
• Actual Study Completion Date: Nov 3, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Melatonin 5 mg Melatonin nightly, beginning within 24 hours of admission	Drug: Melatonin; 5 mg Melatonin nightly, beginning within 24 hours of admission
Placebo Comparator: Cellulose Microcrystylline Blue capsule matching the melatonin arm	Other: Placebo; Blue capsule matching the melatonin arm; Other Names: Cellulose Microcrystylline

Outcome Measures

Primary Outcome Measures

1. Delirium [length of hospitalization, not to exceed 14 days]

   Delirium is defined by the Short Form Confusion Assessment Method (CAM). There must be inattention and either an acute or fluctuating course plus either disorganized thinking or an altered level of consciousness to be diagnosed with delirium. Presented is a count of individuals with reported delirium during hospitalization.

Secondary Outcome Measures

1. Length of Hospital Stay [from day of admission to completion of acute care, not to exceed 30 days]

   Length of stay is defined as the total time hospitalized for the acute illness (in days).

2. Days Utilizing Restraints [length of hospitalization, not to exceed 14 days]

   Days utilizing restraints is defined as the number of days restraints were applied because of delirium in the first 14 days of hospitalization.

3. Number of Delirium Anti-psychotic Drug Doses Utilized for Delirium During the First 14 Days of Hospitalization. [length of hospitalization, not to exceed 14 days]

   Number of delirium anti-psychotic drug doses given for symptoms of delirium. Presented are the number of doses per days of hospitalization.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Inpatient admission to a general internal medicine service

Exclusion Criteria:

• expected lifespan or length of stay ≤ 48 hours

• Non-English speaking

• Already taking melatonin or ramelteon at the time of randomization

• Presence of delirium at the time of randomization

• Unable to take oral medications

• Subject or proxy unable to provide informed consent within 18 hours of invitation or 24 hours of admission

• ALT or AST (Liver function tests) > 3 times the upper limit of normal

• Taking warfarin, nifedipine or fluvoxamine

• Allergy to melatonin

• Unable to recall 3 words after distraction by naming the days of the week backwards beginning with Sunday

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale New Haven Hospital, Saint Raphael Campus	New Haven	Connecticut	United States	06511

Sponsors and Collaborators

• Yale University

Investigators

• Principal Investigator: Stephen A Atlas, M.D., Yale University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 30, 2017

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.
• de Jonghe A, Korevaar JC, van Munster BC, de Rooij SE. Effectiveness of melatonin treatment on circadian rhythm disturbances in dementia. Are there implications for delirium? A systematic review. Int J Geriatr Psychiatry. 2010 Dec;25(12):1201-8. doi: 10.1002/gps.2454. Review.
• de Jonghe A, van Munster BC, Goslings JC, Kloen P, van Rees C, Wolvius R, van Velde R, Levi M, de Haan RJ, de Rooij SE; Amsterdam Delirium Study Group. Effect of melatonin on incidence of delirium among patients with hip fracture: a multicentre, double-blind randomized controlled trial. CMAJ. 2014 Oct 7;186(14):E547-56. doi: 10.1503/cmaj.140495. Epub 2014 Sep 2.
• 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.
• Inouye SK. Delirium in older persons. N Engl J Med. 2006 Mar 16;354(11):1157-65. Review. Erratum in: N Engl J Med. 2006 Apr 13;354(15):1655.
• Miller MO. Evaluation and management of delirium in hospitalized older patients. Am Fam Physician. 2008 Dec 1;78(11):1265-70. Review.
• Sultan SS. Assessment of role of perioperative melatonin in prevention and treatment of postoperative delirium after hip arthroplasty under spinal anesthesia in the elderly. Saudi J Anaesth. 2010 Sep;4(3):169-73. doi: 10.4103/1658-354X.71132.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT02654314
• Other Study ID Numbers: 1601017038
• First Posted: Jan 13, 2016
• Last Update Posted: Mar 21, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Yale University: prevention; delirium; in-patients; melatonin,
• Additional relevant MeSH terms: Delirium; Melatonin

Study Results

Participant Flow

Arm/Group Title	Melatonin	Cellulose Microcrystylline
Arm/Group Description	5 mg Melatonin nightly, beginning within 24 hours of admission Melatonin	Blue capsule matching the melatonin arm Melatonin
Period Title: Overall Study
STARTED	136	141
COMPLETED	136	141
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Melatonin	Cellulose Microcrystylline	Total
Arm/Group Description	5 mg Melatonin nightly, beginning within 24 hours of admission Melatonin	Blue capsule matching the melatonin arm Melatonin	Total of all reporting groups
Overall Participants	136	141	277
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	77.98 (8.53)	78.99 (8.40)	78.49 (8.46)
Sex: Female, Male (Count of Participants)
Female	78 57.4%	67 47.5%	145 52.3%
Male	58 42.6%	74 52.5%	132 47.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 2.2%	6 4.3%	9 3.2%
Not Hispanic or Latino	132 97.1%	135 95.7%	267 96.4%
Unknown or Not Reported	1 0.7%	0 0%	1 0.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 0.7%	0 0%	1 0.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	14 10.3%	18 12.8%	32 11.6%
White	117 86%	119 84.4%	236 85.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	4 2.9%	4 2.8%	8 2.9%
Region of Enrollment (participants) [Number]
United States	136 100%	141 100%	277 100%

Outcome Measures

1. Primary Outcome

Title	Delirium
Description	Delirium is defined by the Short Form Confusion Assessment Method (CAM). There must be inattention and either an acute or fluctuating course plus either disorganized thinking or an altered level of consciousness to be diagnosed with delirium. Presented is a count of individuals with reported delirium during hospitalization.
Time Frame	length of hospitalization, not to exceed 14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Melatonin	Cellulose Microcrystylline
Arm/Group Description	5 mg Melatonin nightly, beginning within 24 hours of admission Melatonin	Blue capsule matching the melatonin arm Melatonin
Measure Participants	136	141
Count of Participants [Participants]	2 1.5%	8 5.7%

2. Secondary Outcome

Title	Length of Hospital Stay
Description	Length of stay is defined as the total time hospitalized for the acute illness (in days).
Time Frame	from day of admission to completion of acute care, not to exceed 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Melatonin	Cellulose Microcrystylline
Arm/Group Description	5 mg Melatonin nightly, beginning within 24 hours of admission Melatonin	Blue capsule matching the melatonin arm Melatonin
Measure Participants	136	141
Mean (Standard Deviation) [days]	4.58 (2.91)	4.71 (3.70)

3. Secondary Outcome

Title	Days Utilizing Restraints
Description	Days utilizing restraints is defined as the number of days restraints were applied because of delirium in the first 14 days of hospitalization.
Time Frame	length of hospitalization, not to exceed 14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Melatonin	Cellulose Microcrystylline
Arm/Group Description	5 mg Melatonin nightly, beginning within 24 hours of admission Melatonin	Blue capsule matching the melatonin arm Melatonin
Measure Participants	136	141
Median (Full Range) [days]	0	0

4. Secondary Outcome

Title	Number of Delirium Anti-psychotic Drug Doses Utilized for Delirium During the First 14 Days of Hospitalization.
Description	Number of delirium anti-psychotic drug doses given for symptoms of delirium. Presented are the number of doses per days of hospitalization.
Time Frame	length of hospitalization, not to exceed 14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Melatonin	Cellulose Microcrystylline
Arm/Group Description	5 mg Melatonin nightly, beginning within 24 hours of admission Melatonin	Blue capsule matching the melatonin arm Melatonin
Measure Participants	136	141
Median (Full Range) [number of doses per days of hospitalizat]	0	0

Adverse Events

Time Frame	Day of admission to completion of acute care, not to exceed 30 day
Arm/Group Title	Melatonin		Cellulose Microcrystylline
Arm/Group Description	5 mg Melatonin nightly, beginning within 24 hours of admission Melatonin		Blue capsule matching the melatonin arm Melatonin
All Cause Mortality
	Melatonin		Cellulose Microcrystylline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/136 (0%)		0/141 (0%)
Serious Adverse Events
	Melatonin		Cellulose Microcrystylline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/136 (0%)		0/141 (0%)
Other (Not Including Serious) Adverse Events
	Melatonin		Cellulose Microcrystylline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/136 (3.7%)		1/141 (0.7%)
Gastrointestinal disorders
Abdominal Pain	1/136 (0.7%)	1	0/141 (0%)	0
Vomiting	1/136 (0.7%)	1	0/141 (0%)	0
Constipation	1/136 (0.7%)	1	0/141 (0%)	0
Nervous system disorders
Somnolence	1/136 (0.7%)	1	0/141 (0%)	0
Headache	1/136 (0.7%)	1	0/141 (0%)	0
Lethargy	0/136 (0%)	0	1/141 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/136 (0.7%)	1	0/141 (0%)	0
Skin and subcutaneous tissue disorders
Rash	1/136 (0.7%)	1	0/141 (0%)	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.