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| ID | Type | Description | Link |
|---|---|---|---|
| 1R21AG050850-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
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This trial focuses on a Phase II randomized masked clinical trial testing the effectiveness and safety of peri-operative administration of ramelteon, a melatonin agonist in the prevention of postoperative delirium.
This trial will randomize older aged patients undergoing general or regional anesthesia for orthopedic surgical procedures to three perioperative doses of a melatonin agonist, ramelteon, and placebo in a masked double blind fashion. The primary outcomes are 1) the incidence of post-operative delirium in the recovery period in the Postoperative Anesthesia Care Unit and on post-operative days 1 and 2 following surgery, and 2) the safety of ramelteon as documented by the presence of adverse events in the follow-up period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment | Experimental | Ramelteon 8 mg oral dose Riboflavin 100 mg (preoperative first dose only) |
|
| Placebo | Placebo Comparator | Capsule Shells filled with microcrystalline cellulose Riboflavin 100 mg (preoperative first dose only - if received as an outpatient) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ramelteon | Drug | 1 pre-operative and 2 nightly postoperative doses of Ramelteon/placebo will be administered |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Delirium During Two Days Following Surgery | Delirium DSM 5 based criteria informed by standardized history gathering, examination, cognitive evaluation using cognitive tests, informant interview, and medical record review) measured during Post-operative Day 1 and/or Day 2 | Up to Post Operative Day 2 |
| Number of Participants With Delirium in the Post Anesthesia Care Unit (PACU) | Delirium (DSM 5 based criteria informed by standardized history gathering, examination, cognitive evaluation using cognitive tests, informant interview, and medical record review) measured once recovered from anesthesia. | Post Operative Day 0: Post Anesthesia Care Unit Following Recovery from Anesthesia |
| Measure | Description | Time Frame |
|---|---|---|
| Delirium Rating Scale - Revised- 98 (DRS-R98) in Delirious Patients | Measure Description: Delirium Rating Scale-Revised-98 (Severity items are rated on a scale of 0-3 and diagnostic items are rated on a scale of 0-2 or 0-3. The minimum score is 0. The maximum possible score for severity items is 39, while the maximum total score is 46. Higher scores indicate more severe delirium; score of 0 indicates no delirium.) Means and Standard Deviations were calculated from the maximum DRS-R98 score documented on Postoperative Day 1 and Day 2 for each participant who became delirious within each treatment arm. |
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Exclusion Criteria:
Delirium diagnosis on the Confusion Assessment Method instrument at baseline
Is unable to give informed consent due to cognitive impairment and a suitable legally authorized representative (LAR) cannot be identified
Declines participation
Current medications that include:
History of ramelteon or riboflavin intolerance
Heavy daily alcohol intake by medical record or history
Current moderate to severe liver failure (as defined by Charlson criteria
Evidence of Systemic Inflammatory Response Syndrome (SIRS) as measured by > 2 criteria8)
Presence of a condition that in the opinion of the PI compromises patient safety or data quality if enrolled in the study.
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| Name | Affiliation | Role |
|---|---|---|
| Karin J Neufeld, MD MPH | Professor - Department of Psychiatry and Behavioral Sciences | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins Bayview Medical Center | Baltimore | Maryland | 21224 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32532654 | Derived | Oh ES, Leoutsakos JM, Rosenberg PB, Pletnikova AM, Khanuja HS, Sterling RS, Oni JK, Sieber FE, Fedarko NS, Akhlaghi N, Neufeld KJ. Effects of Ramelteon on the Prevention of Postoperative Delirium in Older Patients Undergoing Orthopedic Surgery: The RECOVER Randomized Controlled Trial. Am J Geriatr Psychiatry. 2021 Jan;29(1):90-100. doi: 10.1016/j.jagp.2020.05.006. Epub 2020 May 16. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment | Ramelteon 8 mg oral dose Riboflavin 100 mg (preoperative first dose only) Ramelteon: 1 pre-operative and 2 nightly postoperative doses of Ramelteon/placebo will be administered Microcrystalline Cellulose: Placebo Comparator Riboflavin 100 mg: Riboflavin will be added to both placebo and active intervention capsules in order to track adherence to dose while taken as an outpatient (i.e. only the first preoperative dose) |
| FG001 | Placebo | Capsule Shells filled with microcrystalline cellulose Riboflavin 100 mg (preoperative first dose only - if received as an outpatient) Microcrystalline Cellulose: Placebo Comparator Riboflavin 100 mg: Riboflavin will be added to both placebo and active intervention capsules in order to track adherence to dose while taken as an outpatient (i.e. only the first preoperative dose) |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Patients randomized to either treatment with ramelteon or placebo
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment | Ramelteon 8 mg oral dose Riboflavin 100 mg (preoperative first dose only) Ramelteon: 1 pre-operative and 2 nightly postoperative doses of Ramelteon/placebo will be administered Microcrystalline Cellulose: Placebo Comparator Riboflavin 100 mg: Riboflavin will be added to both placebo and active intervention capsules in order to track adherence to dose while taken as an outpatient (i.e. only the first preoperative dose) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Delirium During Two Days Following Surgery | Delirium DSM 5 based criteria informed by standardized history gathering, examination, cognitive evaluation using cognitive tests, informant interview, and medical record review) measured during Post-operative Day 1 and/or Day 2 | Posted | Count of Participants | Participants | Up to Post Operative Day 2 |
|
30-day follow-up after surgery
All adverse events (AE and SAE) were collected from the medical record and daily patient assessment using a customized instrument ("Health Questionnaire") which systematically probed for known side effects (fatigue, headache and next day somnolence).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment | Ramelteon 8 mg oral dose Riboflavin 100 mg (preoperative first dose only) Ramelteon: 1 pre-operative and 2 nightly postoperative doses of Ramelteon/placebo will be administered Microcrystalline Cellulose: Placebo Comparator Riboflavin 100 mg: Riboflavin will be added to both placebo and active intervention capsules in order to track adherence to dose while taken as an outpatient (i.e. only the first preoperative dose) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bigeminy | Cardiac disorders | Systematic Assessment | Bigeminy noted during recovery from anesthesia |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Flushing | Skin and subcutaneous tissue disorders | Systematic Assessment | Facial Flushing |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Karin Neufeld MD MPH: PI of Trial | Johns Hopkins University School of Medicine | 410-550-0197 | kneufel2@jhmi.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 12, 2019 | May 22, 2020 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jul 12, 2019 | May 22, 2020 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D003693 | Delirium |
| D019965 | Neurocognitive Disorders |
| D055191 | Delayed Emergence from Anesthesia |
| D060825 | Cognitive Dysfunction |
| D000071257 | Emergence Delirium |
| ID | Term |
|---|---|
| D003221 | Confusion |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C495910 | ramelteon |
| C109691 | microcrystalline cellulose |
| D012256 | Riboflavin |
| ID | Term |
|---|---|
| D005415 | Flavins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| Microcrystalline Cellulose | Drug | Placebo Comparator |
|
| Riboflavin 100 mg | Drug | Riboflavin will be added to both placebo and active intervention capsules in order to track adherence to dose while taken as an outpatient (i.e. only the first preoperative dose) |
|
|
| Postoperative Day 1 and Day 2 |
| Developed delirium preoperatively |
|
| BG001 | Placebo | Capsule Shells filled with microcrystalline cellulose Riboflavin 100 mg (preoperative first dose only - if received as an outpatient) Microcrystalline Cellulose: Placebo Comparator Riboflavin 100 mg: Riboflavin will be added to both placebo and active intervention capsules in order to track adherence to dose while taken as an outpatient (i.e. only the first preoperative dose) |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants | No |
|
| Region of Enrollment | Number | participants |
|
| DRS-R98 Total | Delirium Rating Scale-Revised-98(23) Severity items are rated on a scale of 0-3 and diagnostic items are rated on a scale of 0-2 or 0-3. The minimum score is 0. The maximum possible score for severity items is 39, while the maximum total score is 46. Higher scores indicate more severe delirium; score of 0 indicates no delirium. | Mean | Standard Deviation | units on a scale |
|
| Placebo |
Capsule Shells filled with microcrystalline cellulose Riboflavin 100 mg (preoperative first dose only - if received as an outpatient) Microcrystalline Cellulose: Placebo Comparator Riboflavin 100 mg: Riboflavin will be added to both placebo and active intervention capsules in order to track adherence to dose while taken as an outpatient (i.e. only the first preoperative dose) |
|
|
| Primary | Number of Participants With Delirium in the Post Anesthesia Care Unit (PACU) | Delirium (DSM 5 based criteria informed by standardized history gathering, examination, cognitive evaluation using cognitive tests, informant interview, and medical record review) measured once recovered from anesthesia. | Posted | Count of Participants | Participants | Post Operative Day 0: Post Anesthesia Care Unit Following Recovery from Anesthesia |
|
|
|
| Secondary | Delirium Rating Scale - Revised- 98 (DRS-R98) in Delirious Patients | Measure Description: Delirium Rating Scale-Revised-98 (Severity items are rated on a scale of 0-3 and diagnostic items are rated on a scale of 0-2 or 0-3. The minimum score is 0. The maximum possible score for severity items is 39, while the maximum total score is 46. Higher scores indicate more severe delirium; score of 0 indicates no delirium.) Means and Standard Deviations were calculated from the maximum DRS-R98 score documented on Postoperative Day 1 and Day 2 for each participant who became delirious within each treatment arm. | Participants With Delirium | Posted | Mean | Standard Deviation | score on a scale | Postoperative Day 1 and Day 2 |
|
|
|
| 0 |
| 41 |
| 3 |
| 41 |
| 13 |
| 41 |
| EG001 | Placebo | Capsule Shells filled with microcrystalline cellulose Riboflavin 100 mg (preoperative first dose only - if received as an outpatient) Microcrystalline Cellulose: Placebo Comparator Riboflavin 100 mg: Riboflavin will be added to both placebo and active intervention capsules in order to track adherence to dose while taken as an outpatient (i.e. only the first preoperative dose) | 0 | 39 | 0 | 39 | 13 | 39 |
|
| Fall | Injury, poisoning and procedural complications | Systematic Assessment | Patient fell 5 days after original surgery |
|
| Hypotension | Cardiac disorders | Systematic Assessment | Hypotension on POD #2 precluding discharge |
|
| Pruritus | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Fainting | Cardiac disorders | Systematic Assessment |
|
| Hypotension | Cardiac disorders | Systematic Assessment |
|
| Reactive leukocytosis | Blood and lymphatic system disorders | Systematic Assessment |
|
| Sinus bradycardia | Cardiac disorders | Systematic Assessment |
|
| Syncope | Cardiac disorders | Systematic Assessment |
|
| Hematuria | Renal and urinary disorders | Systematic Assessment |
|
| Urinary incontinence | Renal and urinary disorders | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Sore throat | Gastrointestinal disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Dizziness | Ear and labyrinth disorders | Systematic Assessment |
|
| Edema in limbs | Blood and lymphatic system disorders | Systematic Assessment |
|
| Eye disorders and eye pain | Eye disorders | Systematic Assessment |
|
| Foot pain | Surgical and medical procedures | Systematic Assessment |
|
| Hyperalertness | Nervous system disorders | Systematic Assessment |
|
| Restlessness | Nervous system disorders | Systematic Assessment |
|
| Muscle cramps | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Surgical procedure - other | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
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| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001523 | Mental Disorders |
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D003072 | Cognition Disorders |
| D006571 | Heterocyclic Compounds |
| D006575 | Heterocyclic Compounds, 3-Ring |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |
| D010860 | Pigments, Biological |
| D001685 | Biological Factors |