<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04483596</url>
  </required_header>
  <id_info>
    <org_study_id>MS-103-2020</org_study_id>
    <nct_id>NCT04483596</nct_id>
  </id_info>
  <brief_title>Melatonin to Decrease the Incidence of Postoperative Delirium in Geriatric Patients</brief_title>
  <official_title>Efficacy of Prophylactic Melatonin to Decrease the Incidence of Postoperative Delirium in Geriatric Patients Undergoing Surgeries Under General Anesthesia. A Randomized Controlled Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cairo University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cairo University</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      POD has been reported to be associated with a large number of risk factors: age as POD occurs&#xD;
      in 10% to 61% of those aged 65 or older, dementia, impaired left ventricular function,&#xD;
      electrolyte disorder, alcoholism, smoking, high perioperative transfusion requirements,&#xD;
      intraoperative pressure fluctuation, and use of benzodiazepine POD occurs mostly in some&#xD;
      types of surgery, such as orthopedic surgeries, major gastrointestinal surgery, and major&#xD;
      cardiovascular surgeries, surgery under general anesthesia, prolonged surgery, emergency&#xD;
      surgery&#xD;
&#xD;
      Previous studies done before to prove the efficacy of melatonin to decrease the incidence of&#xD;
      postoperative delirium in patients with multiple risk factors for POD as traumatic geriatric&#xD;
      patients were concerned only with the type of surgery as hip replacement or with spinal&#xD;
      anesthesia but no study was done before to assess the prophylactic effect of melatonin to&#xD;
      decrease the incidence of postoperative delirium in geriatric patients under general&#xD;
      anesthesia ,which represents an independent risk factor for POD. So,this double blinded RCT&#xD;
      will try to fill this gap in literature.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      POD has been reported to be associated with a large number of risk factors: age as POD occurs&#xD;
      in 10% to 61% of those aged 65 or older, dementia, impaired left ventricular function,&#xD;
      electrolyte disorder, alcoholism, smoking, high perioperative transfusion requirements,&#xD;
      intraoperative pressure fluctuation, and use of benzodiazepine POD occurs mostly in some&#xD;
      types of surgery, such as orthopedic surgeries, major gastrointestinal surgery, and major&#xD;
      cardiovascular surgeries, surgery under general anesthesia, prolonged surgery, emergency&#xD;
      surgery&#xD;
&#xD;
      Previous studies done before to prove the efficacy of melatonin to decrease the incidence of&#xD;
      postoperative delirium in patients with multiple risk factors for POD as traumatic geriatric&#xD;
      patients were concerned only with the type of surgery as hip replacement or with spinal&#xD;
      anesthesia but no study was done before to assess the prophylactic effect of melatonin to&#xD;
      decrease the incidence of postoperative delirium in geriatric patients under general&#xD;
      anesthesia ,which represents an independent risk factor for POD. So,this double blinded RCT&#xD;
      will try to fill this gap in literature.&#xD;
&#xD;
      Aim of the study:&#xD;
&#xD;
      To prove the efficacy of melatonin to decrease the incidence of postoperative delirium after&#xD;
      surgeries under general anesthesia in geriatric patients.&#xD;
&#xD;
      Methodology After approval of the Research Ethics Committee and written informed consent from&#xD;
      all patients, A randomized, prospective, controlled, double blind study of the prophylactic&#xD;
      effect of melatonin on postoperative delirium in geriatric patients undergoing surgeries&#xD;
      under general anesthesia will be conducted on 100 patients allocated into 2 equal groups. The&#xD;
      study will be conducted at Cairo University Hospitals, in all surgical units.&#xD;
&#xD;
      Randomization: Patients who meet all the inclusion criteria will be randomized to either&#xD;
      Group M (Melatonin group) or Group C (Control group) by using computer generated random&#xD;
      numbers with closed sealed envelope.&#xD;
&#xD;
      All patients will fast according to standard rules and will be assessed by an&#xD;
      anesthesiologist at the night before the surgery.&#xD;
&#xD;
      All patients will be screened at that time by Abbreviated Mental Test (AMT) ,where patients&#xD;
      having scores &lt; 6 will be considered to have postoperative delirium.This test has been&#xD;
      recommended for routine assessment of cognitive function in the elderly by the Royal College&#xD;
      of Physicians and the British Geriatric Society.&#xD;
&#xD;
      Questionnare (score) Each scores one point&#xD;
&#xD;
        1. Age&#xD;
&#xD;
        2. Time (to nearest hour)&#xD;
&#xD;
        3. Address for recall at end of test (Ask patient to repeat the address to ensure it has&#xD;
           been heard correctly)&#xD;
&#xD;
        4. Year&#xD;
&#xD;
        5. Name of hospital&#xD;
&#xD;
        6. Recognition of two persons (e.g. doctor, nurse)&#xD;
&#xD;
        7. Date of birth&#xD;
&#xD;
        8. Year of any famous event e.g: the last Egyptian revolution&#xD;
&#xD;
        9. Name of the present monarch&#xD;
&#xD;
       10. Count backwards from 20 to 1&#xD;
&#xD;
      Group M (Melatonin group): will receive 5 mg melatonin orally at 9 p.m. the night before&#xD;
      surgery and another 5 mg melatonin with 15 ml of plain water 30 min before operation and 5 mg&#xD;
      melatonin at 9 p.m. in the day of operation and for the first three postoperative days.&#xD;
&#xD;
      Group C (Control group): received a placebo in the form of one tablet of 500 mg paracetamol&#xD;
      that packaged the same way as melatonin at the same times.&#xD;
&#xD;
      The anesthesia residents who will administer the drug and assess Abbreviated Mental Test(AMT)&#xD;
      score postoperatively will be blinded to the allocation regimen.&#xD;
&#xD;
      On arrival to the preparation room, wide bore IV cannula will be inserted in the nondominant&#xD;
      hand, sedation will be assessed by Ramsay sedation scale,with grades from 1 to 6&#xD;
      where:1-Patient awake, anxious, agitated, or restless ,2- Patient awake, cooperative,&#xD;
      orientated, and tranquil ,3- Patient drowsy, with response to commands ,4- Patient asleep,&#xD;
      brisk response to glabella tap or loud auditory stimulus ,5- Patient asleep, sluggish&#xD;
      response to stimulus ,6- Patient has no response to firm nail-bed pressure or other noxious&#xD;
      stimuli. patients with score &gt; 4 will be excluded from the study.&#xD;
&#xD;
      All Patients will be monitored with five lead ECG, noninvasive blood pressure, oxygen&#xD;
      saturation, capnography and baseline HR,SBP,DBP,MAP,oxygen saturation,ETCO2 , and urine&#xD;
      output will be recorded then every 10 minutes until 30 minutes postextubation. Induction of&#xD;
      anesthesia will be done with fentanyl (2 mic/kg), propofol (1-2 mg/kg), atracurium (0.5&#xD;
      mg/kg). Intubation will be done with oral cuffed endotracheal tube size 6.5-7 mm ID for&#xD;
      females and 7.5-8 mm ID for males and then a urinary catheter will be inserted. Anesthesia&#xD;
      will be maintained with isoflurane (0.75- 1.15%), incremental doses of atracurium every 20&#xD;
      minutes and 1 mic/kg fentanyl IV if HR and/or BP increased 20% or more from baseline in&#xD;
      response to surgical stimulation.&#xD;
&#xD;
      After surgery, patients will be transferred to PACU. Abbreviated Mental Test (AMT) scores&#xD;
      will be reported after recovery from anesthesia (PACU AMT) and in the same day 6 hours after&#xD;
      operation (Day-0) and in the following three postoperative days (Day-1, Day-2 and Day-3) at&#xD;
      the same hour of assessment in day 0. Patients having scores &lt; 6 will be considered to have&#xD;
      postoperative delirium, and will be assessed by a psychiatrist for further management.&#xD;
&#xD;
      Postoperative pain will be managed by IV 1g paracetamol every 6 hours and 50 mg diclofenac&#xD;
      sodium oral every 12 hours with rescue analgesia of IV nalbuphine with 0.25 mg/kg not&#xD;
      exceeding 0.5 mg/kg every 6 hours when the numerical rating score (NRS) or advanced dementia&#xD;
      scale (PAINAD)(if the patient developed delirium) &gt;4.NRS or PAINAD will be evaluated&#xD;
      according to at times 0-30 minutes 2, 4,8, 12, 18 and 24 hours. The &quot;zero&quot; point of time will&#xD;
      be the moment the patient recovered from general anesthesia&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 30, 2020</start_date>
  <completion_date type="Actual">December 3, 2020</completion_date>
  <primary_completion_date type="Actual">December 1, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>postoperative delirium</measure>
    <time_frame>3 postoperative days</time_frame>
    <description>Detection of the difference in incidence of POD between melatonin group and control group using the Abbreviated Mental Test (AMT)</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">100</enrollment>
  <condition>Postoperative Delirium</condition>
  <arm_group>
    <arm_group_label>M</arm_group_label>
    <description>will receive 5 mg melatonin orally at 9 p.m. the night before surgery and another 5 mg melatonin with 15 ml of plain water 30 min before operation and 5 mg melatonin at 9 p.m. in the day of operation and for the first three postoperative days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>C</arm_group_label>
    <description>received a placebo in the form of one tablet of 500 mg paracetamol that packaged the same way as melatonin at the same times</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>melatonin effect on the Abbreviated Mental Test</intervention_name>
    <description>Questionnare&#xD;
Age&#xD;
Time (to nearest hour)&#xD;
Address for recall at end of test (Ask patient to repeat the address to ensure it has been heard correctly)&#xD;
Year&#xD;
Name of hospital&#xD;
Recognition of two persons (e.g. doctor, nurse)&#xD;
Date of birth&#xD;
Year of any famous event e.g: the last Egyptian revolution&#xD;
Name of the present monarch&#xD;
Count backwards from 20 to 1</description>
    <arm_group_label>C</arm_group_label>
    <arm_group_label>M</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        geriatric patients undergoing surgeries under general anesthesia&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ASA physical status I-II&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  ASA physical status ≥ III.&#xD;
&#xD;
          -  Allergy to the study drugs or one of their ingredients&#xD;
&#xD;
          -  Patients with Abbreviated Mental Test (AMT) score of&lt; 6 ,&#xD;
&#xD;
          -  illiterate people,&#xD;
&#xD;
          -  preoperative sedation score &gt;4,&#xD;
&#xD;
          -  History of alcohol abuse,&#xD;
&#xD;
          -  Sensory impairment (blindness, deafness),&#xD;
&#xD;
          -  Severe anemia (hematocrit&lt;27%),&#xD;
&#xD;
          -  Intracranial events (stroke, bleeding, infection),&#xD;
&#xD;
          -  Fluid or electrolyte disturbances including dehydration, hyponatremia, hypernatremia,&#xD;
&#xD;
          -  Acute cardiac events: myocardial infarction, congestive heart failure exacerbation,&#xD;
             arrhythmia,&#xD;
&#xD;
          -  Acute pulmonary events: asthma or chronic obstructive pulmonary disease exacerbation,&#xD;
             pulmonary embolism, hypoxemia, hypercarbia -,Medications Anticonvulsants,&#xD;
             Antidepressants, Antihistamines, Antiparkinsonian agents, Antipsychotics. And history&#xD;
             of chronic sedative hypnotic use &gt;3 times/week during a month prior to surgery&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <location>
    <facility>
      <name>Cairo University hospitals</name>
      <address>
        <city>Cairo</city>
        <state>Manial</state>
        <zip>12511</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <reference>
    <citation>Jankowski CJ, Trenerry MR, Cook DJ, Buenvenida SL, Stevens SR, Schroeder DR, Warner DO. Cognitive and functional predictors and sequelae of postoperative delirium in elderly patients undergoing elective joint arthroplasty. Anesth Analg. 2011 May;112(5):1186-93. doi: 10.1213/ANE.0b013e318211501b. Epub 2011 Mar 17.</citation>
    <PMID>21415433</PMID>
  </reference>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>July 20, 2020</study_first_submitted>
  <study_first_submitted_qc>July 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 23, 2020</study_first_posted>
  <last_update_submitted>December 19, 2020</last_update_submitted>
  <last_update_submitted_qc>December 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cairo University</investigator_affiliation>
    <investigator_full_name>Sherif Abdullah Mohamed</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>melatonin</keyword>
  <keyword>delirium</keyword>
  <keyword>geriatrics</keyword>
  <keyword>general anesthesia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Delirium</mesh_term>
    <mesh_term>Emergence Delirium</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melatonin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>not to share</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04483596
org study id: MS-103-2020
nct id: NCT04483596
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
POD has been reported to be associated with a large number of risk factors: age as POD occurs
      in 10% to 61% of those aged 65 or older, dementia, impaired left ventricular function,
      electrolyte disorder, alcoholism, smoking, high perioperative transfusion requirements,
      intraoperative pressure fluctuation, and use of benzodiazepine POD occurs mostly in some
      types of surgery, such as orthopedic surgeries, major gastrointestinal surgery, and major
      cardiovascular surgeries, surgery under general anesthesia, prolonged surgery, emergency
      surgery

      Previous studies done before to prove the efficacy of melatonin to decrease the incidence of
      postoperative delirium in patients with multiple risk factors for POD as traumatic geriatric
      patients were concerned only with the type of surgery as hip replacement or with spinal
      anesthesia but no study was done before to assess the prophylactic effect of melatonin to
      decrease the incidence of postoperative delirium in geriatric patients under general
      anesthesia ,which represents an independent risk factor for POD. So,this double blinded RCT
      will try to fill this gap in literature.
POD has been reported to be associated with a large number of risk factors: age as POD occurs
      in 10% to 61% of those aged 65 or older, dementia, impaired left ventricular function,
      electrolyte disorder, alcoholism, smoking, high perioperative transfusion requirements,
      intraoperative pressure fluctuation, and use of benzodiazepine POD occurs mostly in some
      types of surgery, such as orthopedic surgeries, major gastrointestinal surgery, and major
      cardiovascular surgeries, surgery under general anesthesia, prolonged surgery, emergency
      surgery

      Previous studies done before to prove the efficacy of melatonin to decrease the incidence of
      postoperative delirium in patients with multiple risk factors for POD as traumatic geriatric
      patients were concerned only with the type of surgery as hip replacement or with spinal
      anesthesia but no study was done before to assess the prophylactic effect of melatonin to
      decrease the incidence of postoperative delirium in geriatric patients under general
      anesthesia ,which represents an independent risk factor for POD. So,this double blinded RCT
      will try to fill this gap in literature.

      Aim of the study:

      To prove the efficacy of melatonin to decrease the incidence of postoperative delirium after
      surgeries under general anesthesia in geriatric patients.

      Methodology After approval of the Research Ethics Committee and written informed consent from
      all patients, A randomized, prospective, controlled, double blind study of the prophylactic
      effect of melatonin on postoperative delirium in geriatric patients undergoing surgeries
      under general anesthesia will be conducted on 100 patients allocated into 2 equal groups. The
      study will be conducted at Cairo University Hospitals, in all surgical units.

      Randomization: Patients who meet all the inclusion criteria will be randomized to either
      Group M (Melatonin group) or Group C (Control group) by using computer generated random
      numbers with closed sealed envelope.

      All patients will fast according to standard rules and will be assessed by an
      anesthesiologist at the night before the surgery.

      All patients will be screened at that time by Abbreviated Mental Test (AMT) ,where patients
      having scores < 6 will be considered to have postoperative delirium.This test has been
      recommended for routine assessment of cognitive function in the elderly by the Royal College
      of Physicians and the British Geriatric Society.

      Questionnare (score) Each scores one point

        1. Age

        2. Time (to nearest hour)

        3. Address for recall at end of test (Ask patient to repeat the address to ensure it has
           been heard correctly)

        4. Year

        5. Name of hospital

        6. Recognition of two persons (e.g. doctor, nurse)

        7. Date of birth

        8. Year of any famous event e.g: the last Egyptian revolution

        9. Name of the present monarch

       10. Count backwards from 20 to 1

      Group M (Melatonin group): will receive 5 mg melatonin orally at 9 p.m. the night before
      surgery and another 5 mg melatonin with 15 ml of plain water 30 min before operation and 5 mg
      melatonin at 9 p.m. in the day of operation and for the first three postoperative days.

      Group C (Control group): received a placebo in the form of one tablet of 500 mg paracetamol
      that packaged the same way as melatonin at the same times.

      The anesthesia residents who will administer the drug and assess Abbreviated Mental Test(AMT)
      score postoperatively will be blinded to the allocation regimen.

      On arrival to the preparation room, wide bore IV cannula will be inserted in the nondominant
      hand, sedation will be assessed by Ramsay sedation scale,with grades from 1 to 6
      where:1-Patient awake, anxious, agitated, or restless ,2- Patient awake, cooperative,
      orientated, and tranquil ,3- Patient drowsy, with response to commands ,4- Patient asleep,
      brisk response to glabella tap or loud auditory stimulus ,5- Patient asleep, sluggish
      response to stimulus ,6- Patient has no response to firm nail-bed pressure or other noxious
      stimuli. patients with score > 4 will be excluded from the study.

      All Patients will be monitored with five lead ECG, noninvasive blood pressure, oxygen
      saturation, capnography and baseline HR,SBP,DBP,MAP,oxygen saturation,ETCO2 , and urine
      output will be recorded then every 10 minutes until 30 minutes postextubation. Induction of
      anesthesia will be done with fentanyl (2 mic/kg), propofol (1-2 mg/kg), atracurium (0.5
      mg/kg). Intubation will be done with oral cuffed endotracheal tube size 6.5-7 mm ID for
      females and 7.5-8 mm ID for males and then a urinary catheter will be inserted. Anesthesia
      will be maintained with isoflurane (0.75- 1.15%), incremental doses of atracurium every 20
      minutes and 1 mic/kg fentanyl IV if HR and/or BP increased 20% or more from baseline in
      response to surgical stimulation.

      After surgery, patients will be transferred to PACU. Abbreviated Mental Test (AMT) scores
      will be reported after recovery from anesthesia (PACU AMT) and in the same day 6 hours after
      operation (Day-0) and in the following three postoperative days (Day-1, Day-2 and Day-3) at
      the same hour of assessment in day 0. Patients having scores < 6 will be considered to have
      postoperative delirium, and will be assessed by a psychiatrist for further management.

      Postoperative pain will be managed by IV 1g paracetamol every 6 hours and 50 mg diclofenac
      sodium oral every 12 hours with rescue analgesia of IV nalbuphine with 0.25 mg/kg not
      exceeding 0.5 mg/kg every 6 hours when the numerical rating score (NRS) or advanced dementia
      scale (PAINAD)(if the patient developed delirium) >4.NRS or PAINAD will be evaluated
      according to at times 0-30 minutes 2, 4,8, 12, 18 and 24 hours. The "zero" point of time will
      be the moment the patient recovered from general anesthesia
observational model: Case-Control
time perspective: Prospective
measure: postoperative delirium
time frame: 3 postoperative days
description: Detection of the difference in incidence of POD between melatonin group and control group using the Abbreviated Mental Test (AMT)
arm group label: M
description: will receive 5 mg melatonin orally at 9 p.m. the night before surgery and another 5 mg melatonin with 15 ml of plain water 30 min before operation and 5 mg melatonin at 9 p.m. in the day of operation and for the first three postoperative days
arm group label: C
description: received a placebo in the form of one tablet of 500 mg paracetamol that packaged the same way as melatonin at the same times
intervention type: Drug
intervention name: melatonin effect on the Abbreviated Mental Test
description: Questionnare
Age
Time (to nearest hour)
Address for recall at end of test (Ask patient to repeat the address to ensure it has been heard correctly)
Year
Name of hospital
Recognition of two persons (e.g. doctor, nurse)
Date of birth
Year of any famous event e.g: the last Egyptian revolution
Name of the present monarch
Count backwards from 20 to 1
arm group label: C
arm group label: M
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 65 Years
maximum age: N/A
facility: 
country: Egypt
citation: Jankowski CJ, Trenerry MR, Cook DJ, Buenvenida SL, Stevens SR, Schroeder DR, Warner DO. Cognitive and functional predictors and sequelae of postoperative delirium in elderly patients undergoing elective joint arthroplasty. Anesth Analg. 2011 May;112(5):1186-93. doi: 10.1213/ANE.0b013e318211501b. Epub 2011 Mar 17.
PMID: 21415433
responsible party type: Principal Investigator
investigator affiliation: Cairo University
investigator full name: Sherif Abdullah Mohamed
investigator title: Principal Investigator
mesh term: Delirium
mesh term: Emergence Delirium
mesh term: Melatonin
sharing ipd: No
ipd description: not to share