<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/NCT03235921</url>
  </required_header>
  <id_info>
    <org_study_id>15316</org_study_id>
    <nct_id>NCT03235921</nct_id>
  </id_info>
  <brief_title>Use of Nitroglycerine to Improve Signs of Poor Peripheral Perfusion in Patients With Traumatic Hemorrhagic Shock</brief_title>
  <official_title>Use of Nitroglycerine to Improve Signs of Poor Peripheral Perfusion in Patients With Traumatic Hemorrhagic Shock</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assiut University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assiut University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Hemorrhagic shock is a pathologic state in which intravascular volume and oxygen delivery are&#xD;
      impaired. During circulatory failure associated with hypovolemia and low cardiac output,&#xD;
      redistribution of blood flow caused by increased vasoconstriction results in decreased&#xD;
      perfusion of the skin.&#xD;
&#xD;
      Skin temperature and capillary refill time has been advocated as a measure of peripheral&#xD;
      perfusion.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Perfusion index (PI) is a non-invasive numerical value of peripheral perfusion obtained from&#xD;
      pulse oximetry, it is an indicator of the pulse strength at the sensor site. The PI's values&#xD;
      range from 0.2% for very weak pulse to 20% for extremely strong pulse according to patient's&#xD;
      physiological conditions and monitoring sites.&#xD;
&#xD;
      Large increases in lactate (i.e. &gt; 5 mmol/L) usually only occur due to hypoperfusion or&#xD;
      muscle activity such as exercise or seizures.&#xD;
&#xD;
      This study will investigate the role of nitroglycerine patch in improving the peripheral&#xD;
      perfusion in poly traumatized patient with hemorrhagic shock for the first time.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>March 2016</start_date>
  <completion_date type="Anticipated">October 2017</completion_date>
  <primary_completion_date type="Anticipated">August 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>To avoid significant hypotension during nitroglycerin administration, each patient was evaluated for adequate intravascularvolume as evidenced by repeated volume challenges(250 mL of crystalloid over 10 minutes) up to appoint at which central venous pressure raised by more than 2 mmHg.&#xD;
When the systolic blood pressure reaches 90mmHg or more we can apply the nitroglycerin patch of 2.5 mg alongside with continuous resuscitation the dose can be doubled according to the change in the peripheral perfusion parameters. Time between administration of nitroglycerin patch and peak of its action will be calculated.&#xD;
Nitroglycerin patch will be removed if the patient developed significant hypotension (mean arterial pressure of less than 50 mm Hg ) however its action may persist up to 45minutes after removal.&#xD;
During the study, infusion rates of noradrenaline or other vasoactive drugs were not changed and no additional fluids were administered.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>increase of perfusion index PI measured by pulse oximeter</measure>
    <time_frame>48hours</time_frame>
    <description>nitroglycerin increases the perfusion index in patients with hemorrhagic shock more than in control group without use of nitroglycerin</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Hemorrhagic Shock</condition>
  <arm_group>
    <arm_group_label>nitroglycerin</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>nitroglycerin patch 5 mg applied to front of chest in each patient at time of admission once.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>control group</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>no drug given to the patients in control group</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nitroglycerin patch 5mg</intervention_name>
    <description>application of the nitroglycerin patch 5 mg to each patient in nitroglycerin group</description>
    <arm_group_label>nitroglycerin</arm_group_label>
    <other_name>nitroglycerin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>no drug given to the control group</description>
    <arm_group_label>control group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age: 20-60 years old. With the patient fully conscious or slightly drowsy.&#xD;
&#xD;
          -  Blood pressure: Systolic blood pressure below 90mmhg ,mean blood pressure below70mmhg&#xD;
             or decrease of systolic blood pressure 40mmhg below normal value.&#xD;
&#xD;
          -  Metabolic acidosis: PH less than 7.35 due to hypoperfusion.&#xD;
&#xD;
          -  Capillary refill time &gt; 4 seconds.&#xD;
&#xD;
          -  Normal body core temperature.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age: below 20 and above 60 years old.&#xD;
&#xD;
          -  Head trauma with Glasco coma score below 14 due to increased intracranial pressure&#xD;
             (stroke, subarachnoid hemorrhage or brain trauma injury).&#xD;
&#xD;
          -  Severe hypotension not responding to fluid therapy.&#xD;
&#xD;
          -  Patient with bilateral ischemic arm injury.&#xD;
&#xD;
          -  Patient with hepatic cell failure&#xD;
&#xD;
          -  Patients admitted to the emergency trauma department after 6 hours of the trauma&#xD;
             event.&#xD;
&#xD;
          -  Preexisting conditions as severe cardiovascular disease, uncontrolled hemorrhage,&#xD;
             failure of central venous catheterization, dialytic procedure anticipated during the&#xD;
             study period.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hassan Kotb, professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>assuit university faculty of medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>medhat sayed, resident</last_name>
    <phone>01095105568</phone>
    <email>medhat_sayed_radwan@hotmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>nedaa abdelhafez, resident</last_name>
    <phone>01111083048</phone>
    <email>medhat_sayed_radwan@hotmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Assuit University Hospital</name>
      <address>
        <city>Assuit</city>
        <country>Egypt</country>
      </address>
    </facility>
    <status>Suspended</status>
  </location>
  <location>
    <facility>
      <name>Assuit University Hospital</name>
      <address>
        <city>Assuit</city>
        <country>Egypt</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <reference>
    <citation>Kauvar DS, Wade CE. The epidemiology and modern management of traumatic hemorrhage: US and international perspectives. Crit Care. 2005;9 Suppl 5(Suppl 5):S1-9. doi: 10.1186/cc3779. Epub 2005 Oct 7.</citation>
    <PMID>16221313</PMID>
  </reference>
  <reference>
    <citation>Bond RF. A review of the skin and muscle hemodynamics during hemorrhagic hypotension and shock. Adv Shock Res. 1982;8:53-70.</citation>
    <PMID>6753542</PMID>
  </reference>
  <reference>
    <citation>Schriger DL, Baraff LJ. Capillary refill--is it a useful predictor of hypovolemic states? Ann Emerg Med. 1991 Jun;20(6):601-5. doi: 10.1016/s0196-0644(05)82375-3.</citation>
    <PMID>2039096</PMID>
  </reference>
  <reference>
    <citation>Steiner MJ, DeWalt DA, Byerley JS. Is this child dehydrated? JAMA. 2004 Jun 9;291(22):2746-54. doi: 10.1001/jama.291.22.2746.</citation>
    <PMID>15187057</PMID>
  </reference>
  <reference>
    <citation>Vincent JL, Ince C, Bakker J. Clinical review: Circulatory shock--an update: a tribute to Professor Max Harry Weil. Crit Care. 2012 Nov 20;16(6):239. doi: 10.1186/cc11510.</citation>
    <PMID>23171699</PMID>
  </reference>
  <reference>
    <citation>Lima AP, Beelen P, Bakker J. Use of a peripheral perfusion index derived from the pulse oximetry signal as a noninvasive indicator of perfusion. Crit Care Med. 2002 Jun;30(6):1210-3. doi: 10.1097/00003246-200206000-00006.</citation>
    <PMID>12072670</PMID>
  </reference>
  <reference>
    <citation>Gladden LB. Lactate metabolism: a new paradigm for the third millennium. J Physiol. 2004 Jul 1;558(Pt 1):5-30. doi: 10.1113/jphysiol.2003.058701. Epub 2004 May 6.</citation>
    <PMID>15131240</PMID>
  </reference>
  <reference>
    <citation>Lopez A, Lorente JA, Steingrub J, Bakker J, McLuckie A, Willatts S, Brockway M, Anzueto A, Holzapfel L, Breen D, Silverman MS, Takala J, Donaldson J, Arneson C, Grove G, Grossman S, Grover R. Multiple-center, randomized, placebo-controlled, double-blind study of the nitric oxide synthase inhibitor 546C88: effect on survival in patients with septic shock. Crit Care Med. 2004 Jan;32(1):21-30. doi: 10.1097/01.CCM.0000105581.01815.C6.</citation>
    <PMID>14707556</PMID>
  </reference>
  <reference>
    <citation>Vincent JL, Zhang H, Szabo C, Preiser JC. Effects of nitric oxide in septic shock. Am J Respir Crit Care Med. 2000 Jun;161(6):1781-5. doi: 10.1164/ajrccm.161.6.9812004.</citation>
    <PMID>10852744</PMID>
  </reference>
  <reference>
    <citation>LILLEHEI RC, LONGERBEAM JK, BLOCH JH, MANAX WG. THE NATURE OF IRREVERSIBLE SHOCK: EXPERIMENTAL AND CLINICAL OBSERVATIONS. Ann Surg. 1964 Oct;160(4):682-710. doi: 10.1097/00000658-196410000-00012. No abstract available.</citation>
    <PMID>14210369</PMID>
  </reference>
  <reference>
    <citation>Nguyen HB, Loomba M, Yang JJ, Jacobsen G, Shah K, Otero RM, Suarez A, Parekh H, Jaehne A, Rivers EP. Early lactate clearance is associated with biomarkers of inflammation, coagulation, apoptosis, organ dysfunction and mortality in severe sepsis and septic shock. J Inflamm (Lond). 2010 Jan 28;7:6. doi: 10.1186/1476-9255-7-6.</citation>
    <PMID>20181046</PMID>
  </reference>
  <reference>
    <citation>SpO2 Monitors with OXISMART® Advanced Signal Processing and Alarm Management Technology. Pulse Oximetry Note Number 9. Masimo signal extraction technology 2008.</citation>
  </reference>
  <reference>
    <citation>American College of Surgeons Committee on Trauma: Advanced TraumaLife Support for Doctors: Instructor Course Manual. 8th ed. Chicago, Ill: AmericanCollege of Surgeons; 2008.</citation>
  </reference>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>August 19, 2016</study_first_submitted>
  <study_first_submitted_qc>July 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 1, 2017</study_first_posted>
  <last_update_submitted>July 31, 2017</last_update_submitted>
  <last_update_submitted_qc>July 31, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assiut University</investigator_affiliation>
    <investigator_full_name>medhat sayed ali</investigator_full_name>
    <investigator_title>Resident at Anaesthesia, ICU and pain management department,Assiut University</investigator_title>
  </responsible_party>
  <keyword>hemorrhagic shock</keyword>
  <keyword>perfusion index</keyword>
  <keyword>lactate</keyword>
  <keyword>nitroglycerin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Shock</mesh_term>
    <mesh_term>Shock, Hemorrhagic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nitroglycerin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</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/NCT03235921
org study id: 15316
nct id: NCT03235921
lead sponsor: 
has dmc: Yes
Hemorrhagic shock is a pathologic state in which intravascular volume and oxygen delivery are
      impaired. During circulatory failure associated with hypovolemia and low cardiac output,
      redistribution of blood flow caused by increased vasoconstriction results in decreased
      perfusion of the skin.

      Skin temperature and capillary refill time has been advocated as a measure of peripheral
      perfusion.
Perfusion index (PI) is a non-invasive numerical value of peripheral perfusion obtained from
      pulse oximetry, it is an indicator of the pulse strength at the sensor site. The PI's values
      range from 0.2% for very weak pulse to 20% for extremely strong pulse according to patient's
      physiological conditions and monitoring sites.

      Large increases in lactate (i.e. > 5 mmol/L) usually only occur due to hypoperfusion or
      muscle activity such as exercise or seizures.

      This study will investigate the role of nitroglycerine patch in improving the peripheral
      perfusion in poly traumatized patient with hemorrhagic shock for the first time.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: To avoid significant hypotension during nitroglycerin administration, each patient was evaluated for adequate intravascularvolume as evidenced by repeated volume challenges(250 mL of crystalloid over 10 minutes) up to appoint at which central venous pressure raised by more than 2 mmHg.
When the systolic blood pressure reaches 90mmHg or more we can apply the nitroglycerin patch of 2.5 mg alongside with continuous resuscitation the dose can be doubled according to the change in the peripheral perfusion parameters. Time between administration of nitroglycerin patch and peak of its action will be calculated.
Nitroglycerin patch will be removed if the patient developed significant hypotension (mean arterial pressure of less than 50 mm Hg ) however its action may persist up to 45minutes after removal.
During the study, infusion rates of noradrenaline or other vasoactive drugs were not changed and no additional fluids were administered.
primary purpose: Treatment
masking: None (Open Label)
measure: increase of perfusion index PI measured by pulse oximeter
time frame: 48hours
description: nitroglycerin increases the perfusion index in patients with hemorrhagic shock more than in control group without use of nitroglycerin
arm group label: nitroglycerin
arm group type: Other
description: nitroglycerin patch 5 mg applied to front of chest in each patient at time of admission once.
arm group label: control group
arm group type: Other
description: no drug given to the patients in control group
intervention type: Drug
intervention name: Nitroglycerin patch 5mg
description: application of the nitroglycerin patch 5 mg to each patient in nitroglycerin group
arm group label: nitroglycerin
other name: nitroglycerin
intervention type: Other
intervention name: placebo
description: no drug given to the control group
arm group label: control group
criteria: 
gender: All
minimum age: 20 Years
maximum age: 60 Years
healthy volunteers: No
last name: Hassan Kotb, professor
role: Principal Investigator
affiliation: assuit university faculty of medicine
last name: medhat sayed, resident
phone: 01095105568
email: medhat_sayed_radwan@hotmail.com
last name: nedaa abdelhafez, resident
phone: 01111083048
email: medhat_sayed_radwan@hotmail.com
facility: 
status: Suspended
facility: 
status: Recruiting
country: Egypt
citation: Kauvar DS, Wade CE. The epidemiology and modern management of traumatic hemorrhage: US and international perspectives. Crit Care. 2005;9 Suppl 5(Suppl 5):S1-9. doi: 10.1186/cc3779. Epub 2005 Oct 7.
PMID: 16221313
citation: Bond RF. A review of the skin and muscle hemodynamics during hemorrhagic hypotension and shock. Adv Shock Res. 1982;8:53-70.
PMID: 6753542
citation: Schriger DL, Baraff LJ. Capillary refill--is it a useful predictor of hypovolemic states? Ann Emerg Med. 1991 Jun;20(6):601-5. doi: 10.1016/s0196-0644(05)82375-3.
PMID: 2039096
citation: Steiner MJ, DeWalt DA, Byerley JS. Is this child dehydrated? JAMA. 2004 Jun 9;291(22):2746-54. doi: 10.1001/jama.291.22.2746.
PMID: 15187057
citation: Vincent JL, Ince C, Bakker J. Clinical review: Circulatory shock--an update: a tribute to Professor Max Harry Weil. Crit Care. 2012 Nov 20;16(6):239. doi: 10.1186/cc11510.
PMID: 23171699
citation: Lima AP, Beelen P, Bakker J. Use of a peripheral perfusion index derived from the pulse oximetry signal as a noninvasive indicator of perfusion. Crit Care Med. 2002 Jun;30(6):1210-3. doi: 10.1097/00003246-200206000-00006.
PMID: 12072670
citation: Gladden LB. Lactate metabolism: a new paradigm for the third millennium. J Physiol. 2004 Jul 1;558(Pt 1):5-30. doi: 10.1113/jphysiol.2003.058701. Epub 2004 May 6.
PMID: 15131240
citation: Lopez A, Lorente JA, Steingrub J, Bakker J, McLuckie A, Willatts S, Brockway M, Anzueto A, Holzapfel L, Breen D, Silverman MS, Takala J, Donaldson J, Arneson C, Grove G, Grossman S, Grover R. Multiple-center, randomized, placebo-controlled, double-blind study of the nitric oxide synthase inhibitor 546C88: effect on survival in patients with septic shock. Crit Care Med. 2004 Jan;32(1):21-30. doi: 10.1097/01.CCM.0000105581.01815.C6.
PMID: 14707556
citation: Vincent JL, Zhang H, Szabo C, Preiser JC. Effects of nitric oxide in septic shock. Am J Respir Crit Care Med. 2000 Jun;161(6):1781-5. doi: 10.1164/ajrccm.161.6.9812004.
PMID: 10852744
citation: LILLEHEI RC, LONGERBEAM JK, BLOCH JH, MANAX WG. THE NATURE OF IRREVERSIBLE SHOCK: EXPERIMENTAL AND CLINICAL OBSERVATIONS. Ann Surg. 1964 Oct;160(4):682-710. doi: 10.1097/00000658-196410000-00012. No abstract available.
PMID: 14210369
citation: Nguyen HB, Loomba M, Yang JJ, Jacobsen G, Shah K, Otero RM, Suarez A, Parekh H, Jaehne A, Rivers EP. Early lactate clearance is associated with biomarkers of inflammation, coagulation, apoptosis, organ dysfunction and mortality in severe sepsis and septic shock. J Inflamm (Lond). 2010 Jan 28;7:6. doi: 10.1186/1476-9255-7-6.
PMID: 20181046
citation: SpO2 Monitors with OXISMART® Advanced Signal Processing and Alarm Management Technology. Pulse Oximetry Note Number 9. Masimo signal extraction technology 2008.
citation: American College of Surgeons Committee on Trauma: Advanced TraumaLife Support for Doctors: Instructor Course Manual. 8th ed. Chicago, Ill: AmericanCollege of Surgeons; 2008.
responsible party type: Principal Investigator
investigator affiliation: Assiut University
investigator full name: medhat sayed ali
investigator title: Resident at Anaesthesia, ICU and pain management department,Assiut University
mesh term: Shock
mesh term: Shock, Hemorrhagic
mesh term: Nitroglycerin
sharing ipd: Yes