Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04335968
Recruitment Status : Recruiting
First Posted : April 7, 2020
Last Update Posted : June 24, 2022
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

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).


Condition or disease Intervention/treatment Phase
Orthopedic Surgery Drug: Melatonin 4 mg Drug: Placebo oral tablet Phase 3

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 790 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Prospective, national multicentric (21 centers), phase III, superiority, comparative randomized (1:1) double-blinded clinical trial with two parallel arms
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Melatonin for Prevention of Postoperative Delirium After Lower Limb Fracture Surgery in Elderly Patients: a Randomized Controlled Trial
Actual Study Start Date : January 23, 2021
Estimated Primary Completion Date : January 31, 2023
Estimated Study Completion Date : April 30, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Delirium Fractures
Drug Information available for: Melatonin

Arm Intervention/treatment
Experimental: 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
Drug: Melatonin 4 mg
melatonin 4mg per os every night, starting the evening before surgery (or 2 hours before emergency surgery) and until day 5 after surgery.

Placebo Comparator: Control group
placebo of this drug with the same schedule, during the same period of time.
Drug: Placebo oral tablet
placebo of this drug with the same schedule, during the same period of time.




Primary Outcome Measures :
  1. Postoperative delirium incidence [ Time Frame: 10 days after surgery ]
    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


Secondary Outcome Measures :
  1. Number of days CAM positive [ Time Frame: 10 days after surgery ]
    CAM will be applied daily during the first 10 days. the minimum 0 and maximum 4 values, and higher scores mean a worse outcome.

  2. Incidence of postoperative sedative or antipsychotic drugs administration from [ Time Frame: 10 days after surgery ]
    Daily review of the medical chart and prescriptions looking for any sedative or antipsychotic drug administration

  3. Incidence of postoperative physical restrain prescription [ Time Frame: 10 days after surgery ]
    Daily review of the medical chart and prescriptions looking for physical restraint prescription.

  4. Incidence of postoperative falls [ Time Frame: 10 days after surgery ]
    Daily review of the medical chart and prescriptions looking for falls, whichever the gravity

  5. Mini Mental State Examination [ Time Frame: 10 days (or end of hospital stay if shorter) ]

    Cognitive testing interview at bedside using the widely used French validated translation of the Mini Mental State Examination.

    the minimum 0 and maximum 30 values, and higher scores mean a better outcome.


  6. Duration of hospital stay [ Time Frame: 30 days after surgery ]
    Daily review of the medical file

  7. 30 days postoperative mortality [ Time Frame: 30 days after surgery ]
    Phone call (or visit for those who had not left the hospital) to the patient or caregivers

  8. 30 days postoperative patient autonomy [ Time Frame: 30 days after surgery ]

    Phone call (or visit for those who had not left the hospital) to the patient or caregivers and evaluation by the Katz Index of activities of daily living.

    The minimum and maximum values are respectively 0 and 6, and higher scores mean a better outcome.


  9. 30 days postoperative Quality of life [ Time Frame: 30 days after surgery ]
    evaluated by EQ5D5L (standardized instrument for measuring generic health status : MOBILITY, SELF-CARE, USUAL ACTIVITIES, PAIN/DISCOMFORT and ANXIETY/ DEPRESSION),) Questionnaire. the minimum 5 and maximum 125 values, and higher scores mean a better outcome.

  10. 30 days postoperative QALYs (quality-adjusted life year) [ Time Frame: 30 days after surgery ]
    QALYs (quality-adjusted life year) are the utility weights for the 30 day period x30/365. the minimum and maximum values are respectively 0 and1, and higher scores mean a better outcome.

  11. Total hospital costs at 30 days [ Time Frame: 30 days after surgery ]
    calculated as the cumulative costs of all admissions (in- and outpatient, home care, rehabilitation) over a 30 day period

  12. Incremental cost effectiveness [ Time Frame: 30 days after surgery ]
    The incremental cost effectiveness ratio is the difference in total costs divided by the difference in the incidence rate of delirium between the two arms

  13. cost utility ratios [ Time Frame: 30 days after surgery ]
    the incremental cost utility ratio is the difference in total costs divided by the difference in QALYs (quality-adjusted life year)

  14. Occurrence of side effects [ Time Frame: 30 days after surgery ]
    During the follow-up, daily interview of the patient and review of the medical chart will be performed, looking for side effects of melatonin.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   70 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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 under tutorship
  • Patient already participating to another interventional study
  • No signed informed consent,
  • No affiliation to a social security regime

Secondary Exclusion Criteria:

Secondary exclusion (before randomization): diagnosis of delirium at the CAM assessment at inclusion, or creatinin clearance <30 ml / min and /or biological signs of hepatocellular insufficiency (bilirubin> 20 umol/l and factor V <70%) if samples not available during the anesthesiologist consultation and so performed after inclusion.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04335968


Contacts
Layout table for location contacts
Contact: Stéphanie Sigaut 1 40 87 59 11 ext +33 stephanie.sigaut@aphp.fr
Contact: Emmanuel Weiss 1 40 87 59 11 ext +33 emmanuel.weiss@aphp.fr

Locations
Layout table for location information
France
hôpital Beaujon Recruiting
Clichy-sous-Bois, France, 93390
Contact: stéphanie sigaut       stephanie.sigaut@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Layout table for investigator information
Principal Investigator: Stéphanie Sigaut APHP
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT04335968    
Other Study ID Numbers: P180594
First Posted: April 7, 2020    Key Record Dates
Last Update Posted: June 24, 2022
Last Verified: March 2022

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
delirium
aging
Perioperative neurocognitive disorders
melatonine
orthopedic surgery
Additional relevant MeSH terms:
Layout table for MeSH terms
Delirium
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Melatonin
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Central Nervous System Depressants