<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/NCT03030911</url>
  </required_header>
  <id_info>
    <org_study_id>N-26-2016</org_study_id>
    <nct_id>NCT03030911</nct_id>
  </id_info>
  <brief_title>Dexmedetomidine vs Midazolam on Resting Energy Expenditure in Critically Ill Patients</brief_title>
  <official_title>The Effect of Dexmedetomidine vs Midazolam on Resting Energy Expenditure in Critically Ill Patients: Randomized Controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cairo University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cairo University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to compare the effect of dexmedetomidine on resting energy&#xD;
      expenditure in relation to the midazolam in critically ill patients using indirect&#xD;
      calorimetry&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Caloric needs in critically-ill patients fluctuate significantly over the course of the&#xD;
      disease which might expose patients to either malnutrition or overfeeding. Malnutrition is&#xD;
      associated with deterioration of lean body mass, poor wound healing, increased risk of&#xD;
      nosocomial infection, and weakened respiratory muscles. On the other hand overfeeding in&#xD;
      medically compromised patients can promote lipogenesis, hyperglycemia, and exacerbation of&#xD;
      respiratory failure. Many factors may affect the resting energy expenditure (REE) through&#xD;
      manipulation of oxygen consumption (VO2).&#xD;
&#xD;
      Sedatives are important contributors to reduction of REE. The postulated mechanism of&#xD;
      sedative-induced reduction of VO2 is inhibition of circulating catecholamine and&#xD;
      pro-inflammatory cytokines.&#xD;
&#xD;
      Dexmedetomidine is a highly selective α2-adrenoceptor agonist. Stimulation of the&#xD;
      α2-adrenoceptor in the central nervous system causes a 60-80% reduction in sympathetic&#xD;
      outflow and endogenous catecholamine levels. It was found that perioperative use of α2&#xD;
      agonists decreased sympathetic activity with subsequent reduction of VO2 and REE. Moreover,&#xD;
      dexmedetomidine, has some anti-inflammatory effect by inhibiting the pro-inflammatory&#xD;
      cytokines which may cause additional reduction of REE in critically ill patient.&#xD;
&#xD;
      Midazolam is another important sedative that is frequently used in critically-ill patient.&#xD;
      Terao et al. found that increasing the depth of sedation using midazolam, decreased oxygen&#xD;
      consumption and REE. However, it remains unclear whether the effect of midazolam on REE is&#xD;
      related to the drug itself or to the depth of sedation.&#xD;
&#xD;
      There is no direct comparison in the literature between dexmedetomidine and midazolam on REE.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2017</start_date>
  <completion_date type="Actual">March 15, 2018</completion_date>
  <primary_completion_date type="Actual">March 10, 2018</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Resting energy expenditure after drug administration</measure>
    <time_frame>The first baseline measurement will be taken before drug administration. The second measurement will be taken 24 hours after drug infusion.</time_frame>
    <description>Resting energy expenditure will be measured using indirect calorimetry via metabolic module on General Electric ventilator</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Heart rate</measure>
    <time_frame>24 hours</time_frame>
    <description>number of heart beats per minute</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>arterial blood pressure</measure>
    <time_frame>24 hours</time_frame>
    <description>arterial blood pressure measured in mmHg</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Richmond agitation and sedation scale</measure>
    <time_frame>24 hours</time_frame>
    <description>range from -5 (unarousable) to +4 (combative)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma interleukin-1β level</measure>
    <time_frame>24 hours</time_frame>
    <description>determined by ELISA using a quantitative sandwich enzyme immunoassay technique</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor necrosis factor-α plasma concentration</measure>
    <time_frame>24 hours</time_frame>
    <description>Enzyme immunoassay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>partial pressure of oxygen in arterial blood</measure>
    <time_frame>24 hours</time_frame>
    <description>the partial pressure of oxygen in arterial blood measured in mmHg</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>VO2</measure>
    <time_frame>24 hours</time_frame>
    <description>the oxygen consumption measured in mL/Kg/min</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>VCO2</measure>
    <time_frame>24 hours</time_frame>
    <description>carbon dioxide production measured in mL/Kg/min</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>end-tidal co2</measure>
    <time_frame>24 hours</time_frame>
    <description>the pressure of carbon dioxide in expired air measured in mmHg</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>cardiac output</measure>
    <time_frame>24 hours</time_frame>
    <description>the amount of blood pumped by the heart during one minute</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Mechanical Ventilation</condition>
  <condition>Dexmedetomidine</condition>
  <condition>Midazolam</condition>
  <condition>Sedation</condition>
  <arm_group>
    <arm_group_label>Dexmedetomidine group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will receive analgesia with fentanyl at a ﬁxed dose of 1 µg.kg.hr-1. Each patient will receive the study drug within 24 hours after intubation. Sedatives used before study enrolment will be discontinued 6 hours prior to the initiation of study drug.&#xD;
Group I patients will have dexmedetomidine (0.075 µg.kg-1.mL-1). Dexmedetomidine infusion will be started at 0.15 µg.kg-1.hr-1 (2 mL.hr-1) and will be adjusted by 0.15 µg.kg-1.h-1 increments to a maximum of 0.75 µg/kg/h (10 ml.h-1)&#xD;
Intervention: indirect calorimetry</description>
  </arm_group>
  <arm_group>
    <arm_group_label>midazolam group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients will receive analgesia with fentanyl at a ﬁxed dose of 1 µg.kg.hr-1. Each patient will receive the study drug within 24 hours after intubation. Sedatives used before study enrolment will be discontinued 6 hours prior to the initiation of study drug.&#xD;
Group II patients will have midazolam (0.5 mg.mL-1). Midazolam will be started at 1 mg.h-1 (2 mL.hr-1) and adjusted by 1 mg.h-1 to a maximum of 5 mg.h-1 (10 mL.h-1). All infusions will be adjusted by increments of 2 mL.hr-1 to maintain blinding. Patients in either group not adequately sedated by the maximum infusion rate of the study medication will receive a bolus dose of fentanyl 0.5 µg.kg-1.&#xD;
Intervention: indirect calorimetry</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexmedetomidine</intervention_name>
    <description>The drug will be administered for sedation and its effect on basal metabolic rate will be investigated</description>
    <arm_group_label>Dexmedetomidine group</arm_group_label>
    <other_name>Precedex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midazolam</intervention_name>
    <description>The drug will be administered for sedation and its effect on basal metabolic rate will be investigated</description>
    <arm_group_label>midazolam group</arm_group_label>
    <other_name>dormicum</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fentanyl</intervention_name>
    <description>The drug will be administered in both groups</description>
    <arm_group_label>Dexmedetomidine group</arm_group_label>
    <arm_group_label>midazolam group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Indirect calorimetry</intervention_name>
    <description>The device will be used for measurement of basal metabolic rate</description>
    <arm_group_label>Dexmedetomidine group</arm_group_label>
    <arm_group_label>midazolam group</arm_group_label>
    <other_name>Calorimetry</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The study will be designed to recruit 30 critically-ill patients who will be admitted&#xD;
             to the surgical ICU for ventilatory support and will be expected to continue for 2&#xD;
             days or longer.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &lt; 18 years old.&#xD;
&#xD;
          -  Pregnant patient.&#xD;
&#xD;
          -  Serious central nervous system pathologies (traumatic brain injury, acute stroke,&#xD;
             uncontrolled seizures).&#xD;
&#xD;
          -  Patient who will require fraction of inspired oxygen more than 0.6.&#xD;
&#xD;
          -  Air leak from the chest tube.&#xD;
&#xD;
          -  Patient with body temperature &gt; 39 Celsius.&#xD;
&#xD;
          -  Acute hepatitis or severe liver disease (Child-Pugh class C).&#xD;
&#xD;
          -  Left ventricular ejection fraction less than 30%.&#xD;
&#xD;
          -  Heart rate less than 50 beats/min.&#xD;
&#xD;
          -  Second or third degree heart block.&#xD;
&#xD;
          -  Systolic pressure &lt; 90 mmHg despite of infusion of 2 vasopressors.&#xD;
&#xD;
          -  Patients with known endocrine dysfunction.&#xD;
&#xD;
          -  Patient with hypothermia&#xD;
&#xD;
          -  Patient on Positive end expiratory pressure more than 14 cmH2o&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mohamed Abdulatif, Professor</last_name>
    <role>Study Chair</role>
    <affiliation>Professor and member of research committee of anesthesia department</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cairo University</name>
      <address>
        <city>Cairo</city>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <reference>
    <citation>Walker RN, Heuberger RA. Predictive equations for energy needs for the critically ill. Respir Care. 2009 Apr;54(4):509-21.</citation>
    <PMID>19327188</PMID>
  </reference>
  <reference>
    <citation>Rubinson L, Diette GB, Song X, Brower RG, Krishnan JA. Low caloric intake is associated with nosocomial bloodstream infections in patients in the medical intensive care unit. Crit Care Med. 2004 Feb;32(2):350-7. doi: 10.1097/01.CCM.0000089641.06306.68.</citation>
    <PMID>14758147</PMID>
  </reference>
  <reference>
    <citation>Covelli HD, Black JW, Olsen MS, Beekman JF. Respiratory failure precipitated by high carbohydrate loads. Ann Intern Med. 1981 Nov;95(5):579-81. doi: 10.7326/0003-4819-95-5-579.</citation>
    <PMID>6794409</PMID>
  </reference>
  <reference>
    <citation>Fung EB. Estimating energy expenditure in critically ill adults and children. AACN Clin Issues. 2000 Nov;11(4):480-97. doi: 10.1097/00044067-200011000-00002.</citation>
    <PMID>11288413</PMID>
  </reference>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>January 19, 2017</study_first_submitted>
  <study_first_submitted_qc>January 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 25, 2017</study_first_posted>
  <last_update_submitted>March 24, 2018</last_update_submitted>
  <last_update_submitted_qc>March 24, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 27, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cairo University</investigator_affiliation>
    <investigator_full_name>Ahmed Hasanin</investigator_full_name>
    <investigator_title>Lecturer of anesthesia and critical care medicine</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Critical Illness</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fentanyl</mesh_term>
    <mesh_term>Midazolam</mesh_term>
    <mesh_term>Dexmedetomidine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </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/NCT03030911
org study id: N-26-2016
nct id: NCT03030911
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The aim of this study is to compare the effect of dexmedetomidine on resting energy
      expenditure in relation to the midazolam in critically ill patients using indirect
      calorimetry
Caloric needs in critically-ill patients fluctuate significantly over the course of the
      disease which might expose patients to either malnutrition or overfeeding. Malnutrition is
      associated with deterioration of lean body mass, poor wound healing, increased risk of
      nosocomial infection, and weakened respiratory muscles. On the other hand overfeeding in
      medically compromised patients can promote lipogenesis, hyperglycemia, and exacerbation of
      respiratory failure. Many factors may affect the resting energy expenditure (REE) through
      manipulation of oxygen consumption (VO2).

      Sedatives are important contributors to reduction of REE. The postulated mechanism of
      sedative-induced reduction of VO2 is inhibition of circulating catecholamine and
      pro-inflammatory cytokines.

      Dexmedetomidine is a highly selective α2-adrenoceptor agonist. Stimulation of the
      α2-adrenoceptor in the central nervous system causes a 60-80% reduction in sympathetic
      outflow and endogenous catecholamine levels. It was found that perioperative use of α2
      agonists decreased sympathetic activity with subsequent reduction of VO2 and REE. Moreover,
      dexmedetomidine, has some anti-inflammatory effect by inhibiting the pro-inflammatory
      cytokines which may cause additional reduction of REE in critically ill patient.

      Midazolam is another important sedative that is frequently used in critically-ill patient.
      Terao et al. found that increasing the depth of sedation using midazolam, decreased oxygen
      consumption and REE. However, it remains unclear whether the effect of midazolam on REE is
      related to the drug itself or to the depth of sedation.

      There is no direct comparison in the literature between dexmedetomidine and midazolam on REE.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Change in Resting energy expenditure after drug administration
time frame: The first baseline measurement will be taken before drug administration. The second measurement will be taken 24 hours after drug infusion.
description: Resting energy expenditure will be measured using indirect calorimetry via metabolic module on General Electric ventilator
measure: Heart rate
time frame: 24 hours
description: number of heart beats per minute
measure: arterial blood pressure
time frame: 24 hours
description: arterial blood pressure measured in mmHg
measure: Richmond agitation and sedation scale
time frame: 24 hours
description: range from -5 (unarousable) to +4 (combative)
measure: Plasma interleukin-1β level
time frame: 24 hours
description: determined by ELISA using a quantitative sandwich enzyme immunoassay technique
measure: Tumor necrosis factor-α plasma concentration
time frame: 24 hours
description: Enzyme immunoassay
measure: partial pressure of oxygen in arterial blood
time frame: 24 hours
description: the partial pressure of oxygen in arterial blood measured in mmHg
measure: VO2
time frame: 24 hours
description: the oxygen consumption measured in mL/Kg/min
measure: VCO2
time frame: 24 hours
description: carbon dioxide production measured in mL/Kg/min
measure: end-tidal co2
time frame: 24 hours
description: the pressure of carbon dioxide in expired air measured in mmHg
measure: cardiac output
time frame: 24 hours
description: the amount of blood pumped by the heart during one minute
arm group label: Dexmedetomidine group
arm group type: Active Comparator
description: Patients will receive analgesia with fentanyl at a ﬁxed dose of 1 µg.kg.hr-1. Each patient will receive the study drug within 24 hours after intubation. Sedatives used before study enrolment will be discontinued 6 hours prior to the initiation of study drug.
Group I patients will have dexmedetomidine (0.075 µg.kg-1.mL-1). Dexmedetomidine infusion will be started at 0.15 µg.kg-1.hr-1 (2 mL.hr-1) and will be adjusted by 0.15 µg.kg-1.h-1 increments to a maximum of 0.75 µg/kg/h (10 ml.h-1)
Intervention: indirect calorimetry
arm group label: midazolam group
arm group type: Placebo Comparator
description: Patients will receive analgesia with fentanyl at a ﬁxed dose of 1 µg.kg.hr-1. Each patient will receive the study drug within 24 hours after intubation. Sedatives used before study enrolment will be discontinued 6 hours prior to the initiation of study drug.
Group II patients will have midazolam (0.5 mg.mL-1). Midazolam will be started at 1 mg.h-1 (2 mL.hr-1) and adjusted by 1 mg.h-1 to a maximum of 5 mg.h-1 (10 mL.h-1). All infusions will be adjusted by increments of 2 mL.hr-1 to maintain blinding. Patients in either group not adequately sedated by the maximum infusion rate of the study medication will receive a bolus dose of fentanyl 0.5 µg.kg-1.
Intervention: indirect calorimetry
intervention type: Drug
intervention name: Dexmedetomidine
description: The drug will be administered for sedation and its effect on basal metabolic rate will be investigated
arm group label: Dexmedetomidine group
other name: Precedex
intervention type: Drug
intervention name: Midazolam
description: The drug will be administered for sedation and its effect on basal metabolic rate will be investigated
arm group label: midazolam group
other name: dormicum
intervention type: Drug
intervention name: Fentanyl
description: The drug will be administered in both groups
arm group label: Dexmedetomidine group
arm group label: midazolam group
intervention type: Device
intervention name: Indirect calorimetry
description: The device will be used for measurement of basal metabolic rate
arm group label: Dexmedetomidine group
arm group label: midazolam group
other name: Calorimetry
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mohamed Abdulatif, Professor
role: Study Chair
affiliation: Professor and member of research committee of anesthesia department
facility: 
country: Egypt
citation: Walker RN, Heuberger RA. Predictive equations for energy needs for the critically ill. Respir Care. 2009 Apr;54(4):509-21.
PMID: 19327188
citation: Rubinson L, Diette GB, Song X, Brower RG, Krishnan JA. Low caloric intake is associated with nosocomial bloodstream infections in patients in the medical intensive care unit. Crit Care Med. 2004 Feb;32(2):350-7. doi: 10.1097/01.CCM.0000089641.06306.68.
PMID: 14758147
citation: Covelli HD, Black JW, Olsen MS, Beekman JF. Respiratory failure precipitated by high carbohydrate loads. Ann Intern Med. 1981 Nov;95(5):579-81. doi: 10.7326/0003-4819-95-5-579.
PMID: 6794409
citation: Fung EB. Estimating energy expenditure in critically ill adults and children. AACN Clin Issues. 2000 Nov;11(4):480-97. doi: 10.1097/00044067-200011000-00002.
PMID: 11288413
responsible party type: Principal Investigator
investigator affiliation: Cairo University
investigator full name: Ahmed Hasanin
investigator title: Lecturer of anesthesia and critical care medicine
mesh term: Critical Illness
mesh term: Fentanyl
mesh term: Midazolam
mesh term: Dexmedetomidine
sharing ipd: Undecided