<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/NCT01715220</url>
  </required_header>
  <id_info>
    <org_study_id>NMCSD.2012.0003</org_study_id>
    <nct_id>NCT01715220</nct_id>
  </id_info>
  <brief_title>Treatment of Suspected Cholelithiasis With Nitroglycerin</brief_title>
  <official_title>Treatment of Suspected Cholelithiasis With Nitroglycerin: a Randomized, Prospective Double-blind Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>United States Naval Medical Center, San Diego</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>United States Naval Medical Center, San Diego</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      ABSTRACT: Sublingual nitroglycerin has been advocated for the treatment of acute pain from&#xD;
      suspected symptomatic cholelithiasis. There is, however, no clinical studies that validate&#xD;
      its use. This study is designed to evaluate the efficacy of nitroglycerine in relieving acute&#xD;
      pain of suspected biliary tract origin.&#xD;
&#xD;
      Nitroglycerin is a potent smooth muscle relaxant used for biliary tract dilation during ERCP,&#xD;
      (Chelly, J) and has been recommended for treatment of biliary colic based on anecdotal&#xD;
      experience and small case reports. Nitroglycerin effect is a result of the nitric oxide&#xD;
      component of the medication which acts as a smooth muscle relaxant in vascular, bronchial,&#xD;
      esophageal and biliary smooth muscles. [McGowan(1936), Chelly (1979),Toyoyama (2001)] The&#xD;
      typical dose of nitroglycerin is 0.4 mg given sublingually in pill form or, more recently, in&#xD;
      a metered spray form. In a case series reported by Hassel (1993), positive response times&#xD;
      ranged from 20 to 60 seconds with duration of action of two to twelve hours. Sublingual&#xD;
      nitroglycerin is most commonly used for treatment of chest pain related to insufficient&#xD;
      cardiac perfusion. It has also been noted to relieve the pain of esophageal spasms.&#xD;
      Nitroglycerin has an excellent safety profile if used in patients with adequate pretreatment&#xD;
      blood pressures. [Newberry (2005), Nitroglycerine (2011), Nitro (2011), Wolters (2009)] This&#xD;
      study proposes to compare sublingual 0.4 mg doses of nitroglycerin to placebo for the initial&#xD;
      treatment of acute pain from suspected symptomatic cholelithiasis&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      General Approach: This study proposes to compare sublingual 0.4 mg doses of nitroglycerin to&#xD;
      placebo for initial treatment for acute pain from suspected symptomatic cholelithiasis.&#xD;
      Patients with right upper quadrant abdominal pain of less than 24 hour duration between ages&#xD;
      18 and 60 years of age will be offered treatment with sublingual nitroglycerin or placebo.&#xD;
      Patients with obstructive hypertrophic cardiomyopathy, pronounced hypovolemia, STEMI or&#xD;
      presumed cardiac chest pain, inferior myocardial infarction with right ventricular&#xD;
      involvement, raised intracranial pressure, cardiac tamponade, and patients taking certain&#xD;
      drugs for erectile dysfunction (phosphodiesterase inhibitors), pregnancy, or with a known&#xD;
      allergy to nitroglycerin will be excluded from the study.&#xD;
&#xD;
      2. Methods: A convenience sample of patients presenting to the Emergency Department will be&#xD;
      randomized to receive either sublingual 0.4 mg doses of nitroglycerin or placebo. Pain prior&#xD;
      to and at two minutes and five minutes after medication administration will be assessed using&#xD;
      a visual analog scale. The medication will be either a 0.4 mg dose of nitroglycerin or a&#xD;
      placebo. If pain is not completely relieved within five minutes, a second dose will be&#xD;
      administered after blood pressure assessment. If the pain is not completely relieved after an&#xD;
      additional two minute and five minute assessment or the pain returns, it will be treated in&#xD;
      the standard manner at the discretion of the treating Emergency Physician. Ancillary studies&#xD;
      and other treatments will be at the discretion of the treating physician. The 0.4mg dose of&#xD;
      nitro has been proven to be a safe and well tolerated dose when administered to our patient&#xD;
      population in treatment of acute coronary syndrome or suspected angina. Our attending,&#xD;
      resident, and nursing staff are very familiar with this dose, the potential side effects of&#xD;
      the medication, and its administration procedure. Therefore, we believe that 0.4mg will be a&#xD;
      optimal starting dose for enrollees in our study.&#xD;
&#xD;
      3. Retrovirology Research: None&#xD;
&#xD;
      4. Investigational Drugs/Devices/Biologics Research: None&#xD;
&#xD;
      5. Statistical Analysis: Demographic information, patient characteristics, assignment to&#xD;
      experimental group, and visual analog pain scale data will be entered into a spreadsheet .&#xD;
      Pain will be recorded per patients at 5 time points: 0, 2, 5, 7, and 10 minutes. Descriptive&#xD;
      statistics will be presented in tables and graphs. Pain scale results will be analyzed by a&#xD;
      two-way (2x5) repeated measures analysis of variance with interaction and post hoc multiple&#xD;
      comparisons. The primary time pair to be tested will be the difference between treatment and&#xD;
      placebo groups in pain reduction from 0 to 2 minutes. The planned sample size is 62, with 31&#xD;
      in the placebo group and 31 in the nitro group. The sample size was calculated with the aid&#xD;
      of Dr Riffenburgh. He agrees with sample size suggested above.&#xD;
&#xD;
      6. Military Relevance / Operational Use, if any: Sublingual nitroglycerin is a standard AMAL&#xD;
      list item for independent providers in most field and operational settings. Relief of biliary&#xD;
      colic can significantly reduce the number of urgent medical evacuations for right upper&#xD;
      quadrant pain. There is also no mental status degradation with the use of nitroglycerin,&#xD;
      unlike the opioids commonly used to treat biliary colic.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>October 2014</start_date>
  <completion_date type="Anticipated">March 2019</completion_date>
  <primary_completion_date type="Anticipated">December 2018</primary_completion_date>
  <phase>Phase 2</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, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>pain relief on visual analog scale</measure>
    <time_frame>two and five minutes</time_frame>
    <description>pain relief assesement at two and five minutes after medication or placebo with standard treatment if inadequate pain relief.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">62</enrollment>
  <condition>COLIC</condition>
  <condition>BILIARY TRACT DISEASES</condition>
  <arm_group>
    <arm_group_label>Sublingual nitroglycerine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Sublingual nitroglycerine followed by pain assessment and if necessary second dose of sublingual nitroglycerine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>sublingual placebo followed by pain assessment and if necessary second dose of sublingual placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>sublingual nitroglycerine</intervention_name>
    <description>A convenience sample of patients presenting to the Emergency Department will be randomized to receive either sublingual 0.4 mg doses of nitroglycerin or placebo. Pain prior to and at two minutes and five minutes after medication administration will be assessed using a visual analog scale. The medication will be either a 0.4 mg dose of nitroglycerin or a placebo. If pain is not completely relieved within five minutes, a second dose will be administered after blood pressure assessment. If the pain is not completely relieved after an additional two minute and five minute assessment or the pain returns, it will be treated in the standard manner at the discretion of the treating Emergency Physician</description>
    <arm_group_label>Sublingual nitroglycerine</arm_group_label>
    <arm_group_label>placebo</arm_group_label>
    <other_name>Nitrolingual</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria: Patients with right upper quadrant abdominal pain of less than 24&#xD;
        hours' duration between ages 18 and 60 years of age will be offered treatment with&#xD;
        sublingual nitroglycerin or placebo.&#xD;
&#xD;
        Exclusion Criteria: Patients with obstructive hypertrophic cardiomyopathy, pronounced&#xD;
        hypovolemia, alcohol use in the last 8 hours, clinical intoxication, STEMI or presumed&#xD;
        cardiac chest pain, inferior myocardial infarction with right ventricular involvement,&#xD;
        raised intracranial pressure, cardiac tamponade and patients taking certain drugs for&#xD;
        erectile dysfunction (phosphodiesterase inhibitors), pregnancy or with a known allergy to&#xD;
        nitroglycerin will be excluded from the study. Patients unable to give consent will be&#xD;
        excluded.&#xD;
&#xD;
        -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Steven J Portouw, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>United States Naval Medical Center, San Diego</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>steven j portouw, MD</last_name>
    <phone>619-532-8274</phone>
    <email>steven.portouw@med.navy.mil</email>
  </overall_contact>
  <location>
    <facility>
      <name>Naval Medical Center San Diego</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92134</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>October 24, 2012</study_first_submitted>
  <study_first_submitted_qc>October 25, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 26, 2012</study_first_posted>
  <last_update_submitted>September 27, 2017</last_update_submitted>
  <last_update_submitted_qc>September 27, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 29, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Nitroglycerin</keyword>
  <keyword>Biliary Colic</keyword>
  <keyword>Cholelithiasis</keyword>
  <keyword>Abdominal Pain.</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cholelithiasis</mesh_term>
    <mesh_term>Cholecystolithiasis</mesh_term>
    <mesh_term>Gallstones</mesh_term>
    <mesh_term>Biliary Tract Diseases</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>No</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/NCT01715220
org study id: NMCSD.2012.0003
nct id: NCT01715220
lead sponsor: 
has dmc: Yes
ABSTRACT: Sublingual nitroglycerin has been advocated for the treatment of acute pain from
      suspected symptomatic cholelithiasis. There is, however, no clinical studies that validate
      its use. This study is designed to evaluate the efficacy of nitroglycerine in relieving acute
      pain of suspected biliary tract origin.

      Nitroglycerin is a potent smooth muscle relaxant used for biliary tract dilation during ERCP,
      (Chelly, J) and has been recommended for treatment of biliary colic based on anecdotal
      experience and small case reports. Nitroglycerin effect is a result of the nitric oxide
      component of the medication which acts as a smooth muscle relaxant in vascular, bronchial,
      esophageal and biliary smooth muscles. [McGowan(1936), Chelly (1979),Toyoyama (2001)] The
      typical dose of nitroglycerin is 0.4 mg given sublingually in pill form or, more recently, in
      a metered spray form. In a case series reported by Hassel (1993), positive response times
      ranged from 20 to 60 seconds with duration of action of two to twelve hours. Sublingual
      nitroglycerin is most commonly used for treatment of chest pain related to insufficient
      cardiac perfusion. It has also been noted to relieve the pain of esophageal spasms.
      Nitroglycerin has an excellent safety profile if used in patients with adequate pretreatment
      blood pressures. [Newberry (2005), Nitroglycerine (2011), Nitro (2011), Wolters (2009)] This
      study proposes to compare sublingual 0.4 mg doses of nitroglycerin to placebo for the initial
      treatment of acute pain from suspected symptomatic cholelithiasis
General Approach: This study proposes to compare sublingual 0.4 mg doses of nitroglycerin to
      placebo for initial treatment for acute pain from suspected symptomatic cholelithiasis.
      Patients with right upper quadrant abdominal pain of less than 24 hour duration between ages
      18 and 60 years of age will be offered treatment with sublingual nitroglycerin or placebo.
      Patients with obstructive hypertrophic cardiomyopathy, pronounced hypovolemia, STEMI or
      presumed cardiac chest pain, inferior myocardial infarction with right ventricular
      involvement, raised intracranial pressure, cardiac tamponade, and patients taking certain
      drugs for erectile dysfunction (phosphodiesterase inhibitors), pregnancy, or with a known
      allergy to nitroglycerin will be excluded from the study.

      2. Methods: A convenience sample of patients presenting to the Emergency Department will be
      randomized to receive either sublingual 0.4 mg doses of nitroglycerin or placebo. Pain prior
      to and at two minutes and five minutes after medication administration will be assessed using
      a visual analog scale. The medication will be either a 0.4 mg dose of nitroglycerin or a
      placebo. If pain is not completely relieved within five minutes, a second dose will be
      administered after blood pressure assessment. If the pain is not completely relieved after an
      additional two minute and five minute assessment or the pain returns, it will be treated in
      the standard manner at the discretion of the treating Emergency Physician. Ancillary studies
      and other treatments will be at the discretion of the treating physician. The 0.4mg dose of
      nitro has been proven to be a safe and well tolerated dose when administered to our patient
      population in treatment of acute coronary syndrome or suspected angina. Our attending,
      resident, and nursing staff are very familiar with this dose, the potential side effects of
      the medication, and its administration procedure. Therefore, we believe that 0.4mg will be a
      optimal starting dose for enrollees in our study.

      3. Retrovirology Research: None

      4. Investigational Drugs/Devices/Biologics Research: None

      5. Statistical Analysis: Demographic information, patient characteristics, assignment to
      experimental group, and visual analog pain scale data will be entered into a spreadsheet .
      Pain will be recorded per patients at 5 time points: 0, 2, 5, 7, and 10 minutes. Descriptive
      statistics will be presented in tables and graphs. Pain scale results will be analyzed by a
      two-way (2x5) repeated measures analysis of variance with interaction and post hoc multiple
      comparisons. The primary time pair to be tested will be the difference between treatment and
      placebo groups in pain reduction from 0 to 2 minutes. The planned sample size is 62, with 31
      in the placebo group and 31 in the nitro group. The sample size was calculated with the aid
      of Dr Riffenburgh. He agrees with sample size suggested above.

      6. Military Relevance / Operational Use, if any: Sublingual nitroglycerin is a standard AMAL
      list item for independent providers in most field and operational settings. Relief of biliary
      colic can significantly reduce the number of urgent medical evacuations for right upper
      quadrant pain. There is also no mental status degradation with the use of nitroglycerin,
      unlike the opioids commonly used to treat biliary colic.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: pain relief on visual analog scale
time frame: two and five minutes
description: pain relief assesement at two and five minutes after medication or placebo with standard treatment if inadequate pain relief.
arm group label: Sublingual nitroglycerine
arm group type: Active Comparator
description: Sublingual nitroglycerine followed by pain assessment and if necessary second dose of sublingual nitroglycerine
arm group label: placebo
arm group type: Placebo Comparator
description: sublingual placebo followed by pain assessment and if necessary second dose of sublingual placebo
intervention type: Drug
intervention name: sublingual nitroglycerine
description: A convenience sample of patients presenting to the Emergency Department will be randomized to receive either sublingual 0.4 mg doses of nitroglycerin or placebo. Pain prior to and at two minutes and five minutes after medication administration will be assessed using a visual analog scale. The medication will be either a 0.4 mg dose of nitroglycerin or a placebo. If pain is not completely relieved within five minutes, a second dose will be administered after blood pressure assessment. If the pain is not completely relieved after an additional two minute and five minute assessment or the pain returns, it will be treated in the standard manner at the discretion of the treating Emergency Physician
arm group label: Sublingual nitroglycerine
arm group label: placebo
other name: Nitrolingual
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Steven J Portouw, MD
role: Principal Investigator
affiliation: United States Naval Medical Center, San Diego
last name: steven j portouw, MD
phone: 619-532-8274
email: steven.portouw@med.navy.mil
facility: 
status: Recruiting
country: United States
responsible party type: Sponsor
mesh term: Cholelithiasis
mesh term: Cholecystolithiasis
mesh term: Gallstones
mesh term: Biliary Tract Diseases
mesh term: Nitroglycerin
sharing ipd: No