Ignite Creation Date:
2024-10-26 @ 3:35 PM
Last Modification Date:
2024-10-26 @ 3:35 PM
Study NCT ID:
NCT06509191
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-07-10
Brief Title:
The Use of Melatonin for Delirium Prevention in Medically Hospitalized Patients
Sponsor:
None
Organization:
None
Study Overview
Official Title:
A Randomized Double-Blind Study of Melatonin Versus Placebo for Delirium Prevention in Medically Hospitalized Patients
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
RESTORE
Brief Summary:
The high prevalence of delirium in hospitalized older adults with significant associated morbidity and mortality emphasize the need for effective prevention strategies Limited trials have explored melatonins potential in preventing delirium among patients admitted to general medical wards Previous trials on melatonins preventive role in medical wards had limitations necessitating a robust double-blinded placebo-controlled design with a larger sample size This randomized double-blind study of melatonin versus placebo aims to investigate the efficacy of melatonin a neurohormone regulating the sleep-wake cycle in preventing delirium among medically hospitalized patients aged 65 or older Given the high prevalence of delirium in this population and its association with adverse outcomes the study seeks to contribute valuable insights into an effective preventive strategy
Detailed Description:
Background
------------------- Delirium a neuropsychiatric syndrome manifests acutely with altered consciousness cognitive impairment and inattention showing a fluctuating course Delirium can present as hyperactive hypoactive or mixed posing challenges for identification especially in the elderly Recent systematic reviews reveal its presence in approximately 50 of hospitalized individuals aged 65 or older with 15-25 developing delirium post major elective surgeries and up to 80 in intensive care units requiring mechanical ventilatory support Various modifiable and non-modifiable risk factors contribute to delirium emphasizing the need for appropriate interventions to reduce risk
The presence of delirium in the elderly has been associated with poor health outcomes A meta-analysis demonstrated a significant association with increased mortality risk at a 22-month follow-up hazard ratio of 195 Unlike several other medical conditions delirium-associated mortality has not declined over the past three decades Delirium is also linked to prolonged hospital stays increased hospital-related complications increased readmission rates and a more significant decline in functional and cognitive abilities potentially leading to dementia development These negative consequences extend to patients and their families contributing to escalated healthcare costs and imposing a substantial burden on individuals and the healthcare system Given the potentially devastating consequences including delayed functional recovery prolonged hospital stays and higher mortality rates careful assessment and treatment of delirium are crucial among hospitalized patients Prevention plays a critical role in reducing the incidence and severity of delirium episodes with a focus on identifying and minimizing contributing factors
The central focus of managing delirium among hospitalized patients primarily involves non-pharmacological interventions including early mobilization controlled use of sedative medications and implementing measures to enhance sleep quality Despite extensive pharmacological interventions no definitive advantages have emerged Haloperidol a prototypical first-generation antipsychotic has been thoroughly studied for delirium treatment yet the evidence supporting its efficacy remains limited Its administration failed to demonstrate significant advantages concerning delirium incidence mortality or length of hospital stay compared to a placebo While olanzapine and quetiapine pose as potential pharmacological alternatives their association with adverse events including metabolic abnormalities and QTc prolongation raises concerns Due to this risk profile and a lack of substantial evidence supporting their effectiveness in preventing andor treating delirium these second-generation antipsychotics have not gained widespread clinical adoption
Although an altered sleep-wake cycle is not a diagnostic criterion for delirium sleep deprivation and delirium share many epidemiologic biochemical and anatomic similarities Nearly 75 of patients with delirium have sleep disorders and the quality of sleep is an integral part of certain delirium screening tools Hence the hypothesis emerges that preventing or treating sleep abnormalities could impact delirium Melatonin a neurohormone principally produced by the pineal gland at night improves the quality of sleep and has hypnotic effects when administered exogenously Studies have shown that melatonin circadian rhythm is disturbed in patients with delirium Melatonin doses exceeding 05 mgday exhibit sleep-promoting effects facilitating resetting the sleep-wake cycle Comparable to glutathione and tocopherol melatonin impact involves scavenging hydroxyl and neutralizing peroxyl radicals thereby reducing cellular damage Due to its antioxidant properties melatonin may offer neuroprotective effects and potentially diminish the risk of neurodegenerative diseases Utilizing melatonin in delirium treatment could thus address circadian rhythm disturbances and impact various hypothesized pathways in delirium development
A systematic review and meta-analysis assessed the prophylactic effect of melatonin receptor agonists MMRAs on postoperative delirium POD in elderly patients Analyzing 11 randomized controlled trials with a total of 1558 patients the results revealed that the MMRA group exhibited a significantly lower occurrence of POD compared to the placebo group risk ratio 070 95 confidence interval 051-097 p 005 I2 59 Subgroup analysis indicated that melatonin significantly reduced POD occurrence supported by moderate-quality evidence whereas ramelteon and tryptophan showed no significant impact Another systematic review and meta-analysis was done to determine the preventive effect of melatonin on delirium in the intensive care unit including six RCTs n2374 patients The overall analysis revealed no significant reduction in delirium incidence among intensive care unit ICU patients However in a subgroup analysis melatonin effectively reduced delirium specifically patients admitted under cardiovascular care unit Secondary outcomes including all-cause mortality length of ICU stay and hospital stay did not exhibit significant differences between the melatonin and placebo groups
A Recent systematic review and metanalysis concluded that using melatonin and ramelteon may decrease the duration and intensity of delirium while reducing the requirement for rescue medications However there is no clear evidence of improvement in the length of hospital stay or the duration of mechanical ventilation MV with the administration of melatonin or ramelteon Notably no safety concerns were identified indicating the apparent safety of both melatonin and ramelteon It is crucial to acknowledge that the results of this systematic review and meta-analysis should be interpreted cautiously due to the high heterogeneity I2 80 and a significant high risk of bias in most of the included studies In a randomized controlled trial comprising 497 patients admitted with acute decompensated heart failure the administration of melatonin at a dosage of 3 mgday for a duration of 7 days demonstrated a significant reduction in the incidence of delirium within the melatonin group compared to the placebo group 270 vs 369 P 0021 Safety assessments revealed comparable occurrences of rhabdomyolysis and abnormal hepatic function in both groups
Most trials assessing the role of melatonin in preventing delirium were conducted in intensive care settings or surgical wards There are very few trials involving hospitalized patients in medical wards
There was randomized double-blinded placebo-controlled study conducted in a London Ontario tertiary care center involved 145 individuals aged 65 or older admitted through the emergency department to medical wards Participants were randomized to receive 05 mg of melatonin or placebo nightly for 14 days or until discharge The study showed lower risk of delirium in the intervention group 120 vs 310 p 0014 Another randomized clinical trial involving hospitalized individuals aged 65 or older n36 received melatonin 33 received placebo administered 3 mg of melatonin The study concluded that the nightly use of 3 mg melatonin did not reduce the incidence of delirium Overall the trial conducted on hospitalized patients -in medical wards-had limitations including small sample sizes variations in medication doses and a lack of assessment regarding healthcare outcomes associated with delirium
Rationale
--------------- The high prevalence of delirium in hospitalized older adults with significant associated morbidity and mortality highlight the need for effective prevention strategies Despite extensive exploration of pharmacological interventions current evidence lacks definitive advantages and widely used antipsychotics present concerns Recognizing the link between sleep disturbances and delirium melatonin a neurohormone regulating the sleep-wake cycle emerges as a promising medication Previous studies demonstrated mixed results with some indicating a prophylactic effect on postoperative delirium while others show no significant impact on delirium incidence in intensive care units Importantly limited trials have explored melatonin39s potential in preventing delirium among patients admitted in general medical wards and previous trials on melatonin39s preventive role in medical wards had limitations necessitating a robust double-blinded placebo-controlled design with a larger sample size
Aim of the study
-------------------------- This study aims to investigate the efficacy of melatonin a neurohormone regulating the sleep-wake cycle in preventing delirium among medically hospitalized patients aged 65 years or older Given the high prevalence of delirium in this population and its
------------------- Delirium a neuropsychiatric syndrome manifests acutely with altered consciousness cognitive impairment and inattention showing a fluctuating course Delirium can present as hyperactive hypoactive or mixed posing challenges for identification especially in the elderly Recent systematic reviews reveal its presence in approximately 50 of hospitalized individuals aged 65 or older with 15-25 developing delirium post major elective surgeries and up to 80 in intensive care units requiring mechanical ventilatory support Various modifiable and non-modifiable risk factors contribute to delirium emphasizing the need for appropriate interventions to reduce risk
The presence of delirium in the elderly has been associated with poor health outcomes A meta-analysis demonstrated a significant association with increased mortality risk at a 22-month follow-up hazard ratio of 195 Unlike several other medical conditions delirium-associated mortality has not declined over the past three decades Delirium is also linked to prolonged hospital stays increased hospital-related complications increased readmission rates and a more significant decline in functional and cognitive abilities potentially leading to dementia development These negative consequences extend to patients and their families contributing to escalated healthcare costs and imposing a substantial burden on individuals and the healthcare system Given the potentially devastating consequences including delayed functional recovery prolonged hospital stays and higher mortality rates careful assessment and treatment of delirium are crucial among hospitalized patients Prevention plays a critical role in reducing the incidence and severity of delirium episodes with a focus on identifying and minimizing contributing factors
The central focus of managing delirium among hospitalized patients primarily involves non-pharmacological interventions including early mobilization controlled use of sedative medications and implementing measures to enhance sleep quality Despite extensive pharmacological interventions no definitive advantages have emerged Haloperidol a prototypical first-generation antipsychotic has been thoroughly studied for delirium treatment yet the evidence supporting its efficacy remains limited Its administration failed to demonstrate significant advantages concerning delirium incidence mortality or length of hospital stay compared to a placebo While olanzapine and quetiapine pose as potential pharmacological alternatives their association with adverse events including metabolic abnormalities and QTc prolongation raises concerns Due to this risk profile and a lack of substantial evidence supporting their effectiveness in preventing andor treating delirium these second-generation antipsychotics have not gained widespread clinical adoption
Although an altered sleep-wake cycle is not a diagnostic criterion for delirium sleep deprivation and delirium share many epidemiologic biochemical and anatomic similarities Nearly 75 of patients with delirium have sleep disorders and the quality of sleep is an integral part of certain delirium screening tools Hence the hypothesis emerges that preventing or treating sleep abnormalities could impact delirium Melatonin a neurohormone principally produced by the pineal gland at night improves the quality of sleep and has hypnotic effects when administered exogenously Studies have shown that melatonin circadian rhythm is disturbed in patients with delirium Melatonin doses exceeding 05 mgday exhibit sleep-promoting effects facilitating resetting the sleep-wake cycle Comparable to glutathione and tocopherol melatonin impact involves scavenging hydroxyl and neutralizing peroxyl radicals thereby reducing cellular damage Due to its antioxidant properties melatonin may offer neuroprotective effects and potentially diminish the risk of neurodegenerative diseases Utilizing melatonin in delirium treatment could thus address circadian rhythm disturbances and impact various hypothesized pathways in delirium development
A systematic review and meta-analysis assessed the prophylactic effect of melatonin receptor agonists MMRAs on postoperative delirium POD in elderly patients Analyzing 11 randomized controlled trials with a total of 1558 patients the results revealed that the MMRA group exhibited a significantly lower occurrence of POD compared to the placebo group risk ratio 070 95 confidence interval 051-097 p 005 I2 59 Subgroup analysis indicated that melatonin significantly reduced POD occurrence supported by moderate-quality evidence whereas ramelteon and tryptophan showed no significant impact Another systematic review and meta-analysis was done to determine the preventive effect of melatonin on delirium in the intensive care unit including six RCTs n2374 patients The overall analysis revealed no significant reduction in delirium incidence among intensive care unit ICU patients However in a subgroup analysis melatonin effectively reduced delirium specifically patients admitted under cardiovascular care unit Secondary outcomes including all-cause mortality length of ICU stay and hospital stay did not exhibit significant differences between the melatonin and placebo groups
A Recent systematic review and metanalysis concluded that using melatonin and ramelteon may decrease the duration and intensity of delirium while reducing the requirement for rescue medications However there is no clear evidence of improvement in the length of hospital stay or the duration of mechanical ventilation MV with the administration of melatonin or ramelteon Notably no safety concerns were identified indicating the apparent safety of both melatonin and ramelteon It is crucial to acknowledge that the results of this systematic review and meta-analysis should be interpreted cautiously due to the high heterogeneity I2 80 and a significant high risk of bias in most of the included studies In a randomized controlled trial comprising 497 patients admitted with acute decompensated heart failure the administration of melatonin at a dosage of 3 mgday for a duration of 7 days demonstrated a significant reduction in the incidence of delirium within the melatonin group compared to the placebo group 270 vs 369 P 0021 Safety assessments revealed comparable occurrences of rhabdomyolysis and abnormal hepatic function in both groups
Most trials assessing the role of melatonin in preventing delirium were conducted in intensive care settings or surgical wards There are very few trials involving hospitalized patients in medical wards
There was randomized double-blinded placebo-controlled study conducted in a London Ontario tertiary care center involved 145 individuals aged 65 or older admitted through the emergency department to medical wards Participants were randomized to receive 05 mg of melatonin or placebo nightly for 14 days or until discharge The study showed lower risk of delirium in the intervention group 120 vs 310 p 0014 Another randomized clinical trial involving hospitalized individuals aged 65 or older n36 received melatonin 33 received placebo administered 3 mg of melatonin The study concluded that the nightly use of 3 mg melatonin did not reduce the incidence of delirium Overall the trial conducted on hospitalized patients -in medical wards-had limitations including small sample sizes variations in medication doses and a lack of assessment regarding healthcare outcomes associated with delirium
Rationale
--------------- The high prevalence of delirium in hospitalized older adults with significant associated morbidity and mortality highlight the need for effective prevention strategies Despite extensive exploration of pharmacological interventions current evidence lacks definitive advantages and widely used antipsychotics present concerns Recognizing the link between sleep disturbances and delirium melatonin a neurohormone regulating the sleep-wake cycle emerges as a promising medication Previous studies demonstrated mixed results with some indicating a prophylactic effect on postoperative delirium while others show no significant impact on delirium incidence in intensive care units Importantly limited trials have explored melatonin39s potential in preventing delirium among patients admitted in general medical wards and previous trials on melatonin39s preventive role in medical wards had limitations necessitating a robust double-blinded placebo-controlled design with a larger sample size
Aim of the study
-------------------------- This study aims to investigate the efficacy of melatonin a neurohormone regulating the sleep-wake cycle in preventing delirium among medically hospitalized patients aged 65 years or older Given the high prevalence of delirium in this population and its
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None