Ignite Creation Date:
2025-12-24 @ 5:44 PM
Ignite Modification Date:
2025-12-25 @ 3:12 PM
Study NCT ID:
NCT04335968
Status:
COMPLETED
Last Update Posted:
2025-09-08
First Post:
2020-02-28
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Melatonin for Prevention of Postoperative Delirium After Lower Limb Fracture Surgery in Elderly Patients
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Study Overview
Official Title:
Melatonin for Prevention of Postoperative Delirium After Lower Limb Fracture Surgery in Elderly Patients: a Randomized Controlled Trial
Status:
COMPLETED
Status Verified Date:
2025-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DELIRLESS
Brief Summary:
Postoperative delirium (POD) is one of the most frequent complications after surgery in elderly patients, affecting between 20 and 40% of patients older than 60 after major surgery. This complication has huge consequences for the patients, families and society: increase of morbidity and mortality, prolonged length of stay, cognitive and functional decline leading to loss of autonomy, and important additional healthcare costs.
Among numerous risk factors identified, perioperative inflammatory stress is a key element in delirium genesis: surgical trauma releases danger signals in systemic circulation, activating immune cells and leading to neuroinflammation.
Melatonin is a neurohormone regulating circadian rhythm. But it also exhibits antioxidant and free radical scavenger properties, and regulates energy metabolism and immune function. It has already demonstrated a neuroprotective potential in various animal models. Its use against delirium is promising: it decreases delirium incidence in elderly patients hospitalized in medical ward, and several studies are now recruiting in ICU.
The hypothesis of the trial is that in a high-risk population, perioperative melatonin can reduce the incidence of POD.
The main objective is to evaluate the effect of perioperative melatonin administration on postoperative delirium incidence in the first 10 days after surgery, in elderly patients (over 70 years old) being hospitalized and scheduled for acute surgery of fractured lower limb (from femoral head to tibial plateau).
This is a prospective, national multicentric (24 centers), phase III, superiority, comparative randomized (1:1) double-blinded clinical trial with two parallel arms:
Experimental group: melatonin 4mg per os every night, starting the evening before surgery (or 2 hours before emergency surgery) and until day 5 after surgery.
Control group: placebo of this drug with the same schedule, during the same period of time.
The patients are aged 70 or older, hospitalized and scheduled for surgery of a severe fracture of a lower limb (from femoral head to tibial plateau).
Among numerous risk factors identified, perioperative inflammatory stress is a key element in delirium genesis: surgical trauma releases danger signals in systemic circulation, activating immune cells and leading to neuroinflammation.
Melatonin is a neurohormone regulating circadian rhythm. But it also exhibits antioxidant and free radical scavenger properties, and regulates energy metabolism and immune function. It has already demonstrated a neuroprotective potential in various animal models. Its use against delirium is promising: it decreases delirium incidence in elderly patients hospitalized in medical ward, and several studies are now recruiting in ICU.
The hypothesis of the trial is that in a high-risk population, perioperative melatonin can reduce the incidence of POD.
The main objective is to evaluate the effect of perioperative melatonin administration on postoperative delirium incidence in the first 10 days after surgery, in elderly patients (over 70 years old) being hospitalized and scheduled for acute surgery of fractured lower limb (from femoral head to tibial plateau).
This is a prospective, national multicentric (24 centers), phase III, superiority, comparative randomized (1:1) double-blinded clinical trial with two parallel arms:
Experimental group: melatonin 4mg per os every night, starting the evening before surgery (or 2 hours before emergency surgery) and until day 5 after surgery.
Control group: placebo of this drug with the same schedule, during the same period of time.
The patients are aged 70 or older, hospitalized and scheduled for surgery of a severe fracture of a lower limb (from femoral head to tibial plateau).
Detailed Description:
Postoperative delirium (POD) is one of the most frequent complications after surgery in elderly patients, affecting between 20 and 40% of patients older than 60 after major surgery. This complication has huge consequences for the patients, families and society: increase of morbidity and mortality, prolonged length of stay, cognitive and functional decline leading to loss of autonomy, and important additional healthcare costs.
Among numerous risk factors identified, perioperative inflammatory stress is a key element in delirium genesis: surgical trauma releases danger signals in systemic circulation, activating immune cells and leading to neuroinflammation. In the brain, especially in hippocampus, proinflammatory cytokines, immune cells recruitment and microglial activation alter synaptic plasticity and lead to acute cognitive dysfunction. Moreover, with aging, an increase in initial neuroinflammatory response and a decrease in subsequent resolution phase are observed.
Melatonin is a neurohormone regulating circadian rhythm. But it also exhibits antioxidant and free radical scavenger properties, and regulates energy metabolism and immune function. It has already demonstrated a neuroprotective potential in various animal models. Its use against delirium is promising: it decreases delirium incidence in elderly patients hospitalized in medical ward, and several studies are now recruiting in ICU. Concerning the perioperative period, only two studies with conflicting results are available. The first one (Sultan, 2010), that has shown that melatonin decreases POD incidence, has strong methodological limitations (no calculated sample size, only 53 patients in melatonin group, all patients, even in the control group received melatonin if they developed POD, etc). In the second one (deJonghe, 2014), melatonin had no effect on POD incidence, but showed a reduction in the proportion of patients with POD exceeding 2 days. These conflicting results emphasize the need for a third RCT, with optimized methodology.
The hypothesis of the trial is that in a high-risk population, perioperative melatonin can reduce the incidence of POD.
The main objective is to evaluate the effect of perioperative melatonin administration on postoperative delirium incidence in the first 10 days after surgery, in elderly patients (over 70 years old) being hospitalized and scheduled for acute surgery of fractured lower limb (from femoral head to tibial plateau).
This is a prospective, national multicentric (24 centers), phase III, superiority, comparative randomized (1:1) double-blinded clinical trial with two parallel arms:
Experimental group: melatonin 4mg per os every night, starting the evening before surgery (or 2 hours before emergency surgery) and until day 5 after surgery.
Control group: placebo of this drug with the same schedule, during the same period of time.
The patients are aged 70 or older, hospitalized and scheduled for surgery of a severe fracture of a lower limb (from femoral head to tibial plateau).
An ancillary study is also planned in this study with the hypothesise that :
* Patients presenting post-operative delirium may exhibit significant perturbations of phenotypic and transcriptomic features of circulating leukocytes, of plasma levels of cytokines, and of oxidative stress level.
* Administration of melatonin may prevent these perturbations.
Ancillary study concerns Beaujon, Bichat and la Pitié centers.
Among numerous risk factors identified, perioperative inflammatory stress is a key element in delirium genesis: surgical trauma releases danger signals in systemic circulation, activating immune cells and leading to neuroinflammation. In the brain, especially in hippocampus, proinflammatory cytokines, immune cells recruitment and microglial activation alter synaptic plasticity and lead to acute cognitive dysfunction. Moreover, with aging, an increase in initial neuroinflammatory response and a decrease in subsequent resolution phase are observed.
Melatonin is a neurohormone regulating circadian rhythm. But it also exhibits antioxidant and free radical scavenger properties, and regulates energy metabolism and immune function. It has already demonstrated a neuroprotective potential in various animal models. Its use against delirium is promising: it decreases delirium incidence in elderly patients hospitalized in medical ward, and several studies are now recruiting in ICU. Concerning the perioperative period, only two studies with conflicting results are available. The first one (Sultan, 2010), that has shown that melatonin decreases POD incidence, has strong methodological limitations (no calculated sample size, only 53 patients in melatonin group, all patients, even in the control group received melatonin if they developed POD, etc). In the second one (deJonghe, 2014), melatonin had no effect on POD incidence, but showed a reduction in the proportion of patients with POD exceeding 2 days. These conflicting results emphasize the need for a third RCT, with optimized methodology.
The hypothesis of the trial is that in a high-risk population, perioperative melatonin can reduce the incidence of POD.
The main objective is to evaluate the effect of perioperative melatonin administration on postoperative delirium incidence in the first 10 days after surgery, in elderly patients (over 70 years old) being hospitalized and scheduled for acute surgery of fractured lower limb (from femoral head to tibial plateau).
This is a prospective, national multicentric (24 centers), phase III, superiority, comparative randomized (1:1) double-blinded clinical trial with two parallel arms:
Experimental group: melatonin 4mg per os every night, starting the evening before surgery (or 2 hours before emergency surgery) and until day 5 after surgery.
Control group: placebo of this drug with the same schedule, during the same period of time.
The patients are aged 70 or older, hospitalized and scheduled for surgery of a severe fracture of a lower limb (from femoral head to tibial plateau).
An ancillary study is also planned in this study with the hypothesise that :
* Patients presenting post-operative delirium may exhibit significant perturbations of phenotypic and transcriptomic features of circulating leukocytes, of plasma levels of cytokines, and of oxidative stress level.
* Administration of melatonin may prevent these perturbations.
Ancillary study concerns Beaujon, Bichat and la Pitié centers.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: