Melatonin for Prevention of Postoperative Delirium After Lower Limb Fracture Surgery in Elderly Patients

NCT04335968 | Completed Phase 3

• 1 other identifier: APHP180594
• Study Type: interventional
• Target: 357
• Locations: 1 country
• Sites: 1

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).

Conditions

Orthopedic Surgery

Keywords

delirium; aging; Perioperative neurocognitive disorders; melatonine; orthopedic surgery

Outcome Measures

Primary Outcomes (1)

• Postoperative delirium incidence

  The Confusion Assessment Method (CAM) score, for patients hospitalized in surgery, or CAM-ICU score, for patients hospitalized in ICU will be applied daily during the first 10 days after surgery or end of hospital stay if shorter

  10 days after surgery

Secondary Outcomes (14)

• Number of days CAM positive

  10 days after surgery

• Incidence of postoperative sedative or antipsychotic drugs administration from

  10 days after surgery

• Incidence of postoperative physical restrain prescription

  10 days after surgery

• Incidence of postoperative falls

  10 days after surgery

• Mini Mental State Examination

  10 days (or end of hospital stay if shorter)

Study Arms (2)

Experimental group

EXPERIMENTAL

melatonin 4mg per os every night, starting the evening before surgery (or 2 hours before emergency surgery) and until day 5 after surgery

Drug: Melatonin 4 mg

Control group

PLACEBO COMPARATOR

placebo of this drug with the same schedule, during the same period of time.

Drug: Placebo oral tablet

Interventions

Melatonin 4 mg DRUG

melatonin 4mg per os every night, starting the evening before surgery (or 2 hours before emergency surgery) and until day 5 after surgery.

Experimental group

Placebo oral tablet DRUG

placebo of this drug with the same schedule, during the same period of time.

Control group

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Demographic criteria: patient 70 years old or older
• Diagnostic criteria: isolated fracture of a lower limb
• Proximal femoral fractures: head, cervical, or trochanteric fractures
• Periprosthetic hip fracture
• Femoral shaft fracture
• Distal femoral fractures: supracondylar or condylar
• Periprosthetic knee fracture
• Tibial plateau fracture
• Treatments/strategies/procedures: scheduled orthopedic surgery (osteosynthesis or arthroplasty)
• proxy or care giver knowing baseline cognitive status of the patient present or reachable by phone for an interview

You may not qualify if:

• Patient already taking Melatonin
• Contraindications and precaution for use of Melatonin administration:
• Hypersensitivity to the active substance or to any of the excipients of Circadin©
• Liver failure (presence of some of the following clinical and biological symptoms: icterus, asterixis, ascites, known esophageal varices, total bilirubin \>20 micromol/L, FV \<70%),
• Cirrhosis (known histological liver fibrosis)
• Renal failure with clearance \<30 ml/min O Autoimmune disease O Hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption syndrome
• Patients taking fluvoxamine, 5- or 8-methoxypsoralen, cimetidine, oestrogenotherapy, quinolones, carbamazepine, rifampicin
• Other concomitant trauma than lower limb fracture(s)
• Surgery scheduled in more than 5 days
• Patient under mechanical ventilation
• Patient refusing to participate
• Patient not talking / understanding French (delirium assessment impossible)
• Patient already participating to another interventional study
• No signed informed consent,
• No affiliation to a social security regime

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

hôpital Beaujon

Clichy-sous-Bois, 93390, France

Location

Related Publications (1)

• Sigaut S, Couffignal C, Esposito-Farese M, Degos V, Molliex S, Boddaert J, Raynaud-Simon A, Durand-Zaleski I, Marcault E, Jacota M, Dahmani S, Paugam-Burtz C, Weiss E. Melatonin for prevention of postoperative delirium after lower limb fracture surgery in elderly patients (DELIRLESS): study protocol for a multicentre randomised controlled trial. BMJ Open. 2021 Dec 24;11(12):e053908. doi: 10.1136/bmjopen-2021-053908.

  PMID: 34952881 DERIVED

MeSH Terms

Conditions

Delirium

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Stéphanie Sigaut

  APHP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, national multicentric (21 centers), phase III, superiority, comparative randomized (1:1) double-blinded clinical trial with two parallel arms

Study Record Dates

• First Submitted: February 28, 2020
• First Posted: April 7, 2020
• Study Start: January 23, 2021
• Primary Completion: April 18, 2025
• Study Completion: April 18, 2025
• Last Updated: September 8, 2025

Record last verified: 2025-05

Locations

FR (1)