<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/NCT03242473</url>
  </required_header>
  <id_info>
    <org_study_id>14-12-FB-0245</org_study_id>
    <nct_id>NCT03242473</nct_id>
  </id_info>
  <brief_title>Comparing the Effects of Lactated Ringers and Normal Saline in Acute Pancreatitis</brief_title>
  <official_title>Mitigating the Inflammatory Response in Acute Pancreatitis With Appropriate Fluid Management; A Randomized Clinical Control Trial Comparing the Effects of Lactated Ringers and Normal Saline</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital Medical Center, Cincinnati</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Children's National Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Children's Hospital of The King's Daughters</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Children's Hospital Medical Center, Cincinnati</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Acute pancreatitis is increasingly common diagnosis in children. Most of the guidelines&#xD;
      related to the details of management of acute pancreatitis are extrapolated from the adult&#xD;
      literature. There is only limited data regarding management of acute pancreatitis in&#xD;
      children. The mainstay of management is bowel and pancreatic rest with significant fluid&#xD;
      support to minimize the effect of the cytokines on the pancreas and other organs. The&#xD;
      standard fluid choices are Lactated Ringer's solution (LR) and normal saline (NS). Currently,&#xD;
      both LR and NS are used at the discretion of the treating physician as the standard of care&#xD;
      for acute pancreatitis. The investigators hope to examine the question of ideal fluid choice&#xD;
      for fluid resuscitation in children with acute pancreatitis by assessing recovery time in the&#xD;
      context of measured inflammatory markers and SIRS status at 24 and 48 hours after admission.&#xD;
      The ideal fluid choice in the initial resuscitation of acute pancreatitis has not been&#xD;
      effectively evaluated before in the pediatric population. Even if there is no statistically&#xD;
      significant difference between the two fluid options, this trial will still provide&#xD;
      clinically significant information.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Acute pancreatitis represents inflammation of the pancreas that has been well identified in&#xD;
      the literature for several centuries. However, the phenomenon has only relatively recently&#xD;
      gained prominence in the pediatric literature. The incidence can be as high as 13 per 100,000&#xD;
      per year, a level which approaches that seen in adults, and the diagnosis has been&#xD;
      increasingly common over the last two decades. It affects all ages of children (including&#xD;
      infants) evidenced by well-established age appropriate diagnostic criteria. The precise&#xD;
      pathophysiological basis of the inflammation is not always as clear. Currently, the&#xD;
      prevailing theory is that there is an insult to the acinar cells of the pancreas likely via&#xD;
      an atypical calcium signal that releases a cascade of cellular activity and that ultimately&#xD;
      results in a disseminated cytokine storm. While there is certainly debate as to the inciting&#xD;
      event to this cascade, one thing that is clear is that extensive end-organ damage can occur&#xD;
      if this cytokine storm reaches systemic circulation. Therefore, the mainstay of management is&#xD;
      bowel (and specifically pancreatic) rest with significant fluid support to minimize or&#xD;
      mitigate the effect of the cytokines on the pancreas and other systemic organs such as the&#xD;
      lungs, heart, and kidneys. The remainder of therapy consists of appropriate analgesia and&#xD;
      antiemetics.&#xD;
&#xD;
      Unfortunately, most of the guidelines related to the details of management of acute&#xD;
      pancreatitis are extrapolated from the adult literature. There is only limited data regarding&#xD;
      management of acute pancreatitis in children. Recently, Wu et al. have shown compelling data&#xD;
      that suggest the choice of fluid for management of acute pancreatitis in adults should be&#xD;
      Lactated Ringers (LR). Their group demonstrated in a small randomized controlled trial&#xD;
      involving 40 adult patients with acute pancreatitis, that the patients randomized to the LR&#xD;
      arm of the study had significantly lower levels of C-reactive protein and Systemic&#xD;
      Inflammatory Response Syndrome (SIRS) markers compared with controls in the normal saline&#xD;
      (NS) group. They proposed that the mechanism for this difference may be related to the more&#xD;
      balanced pH of LR which might prevent, or at least further buffer, the systemic inflammation&#xD;
      that is triggered by the release of the offending cytokines from the pancreas. Currently,&#xD;
      both LR and NS are used at both Children's Hospital of The King's Daughters (CHKD) and&#xD;
      Children's National Health System (CNHS) at the discretion of the attending physician as the&#xD;
      standard of care for acute pancreatitis. The investigators hope to examine the question of&#xD;
      ideal fluid choice for fluid resuscitation in children with acute pancreatitis by assessing&#xD;
      recovery time in the context of measured inflammatory markers and SIRS status at 24 and 48&#xD;
      hours after admission.&#xD;
&#xD;
      This is a prospective randomized trial of pediatric patients in the emergency department (ED)&#xD;
      or inpatient ward diagnosed with acute pancreatitis. Patients meeting the study inclusion&#xD;
      criteria will be identified by an ED or inpatient physician. The ED or inpatient physician&#xD;
      will ask the eligible patient/parent if they are interested in hearing about the study. If&#xD;
      the eligible patient/parent is interested in hearing information about the study, the ED or&#xD;
      inpatient ward will notify the PI via telephone or page. The PI will come to the eligible&#xD;
      patient's room to explain the study and answer any questions, or the PI will page a research&#xD;
      team member to do so. If the patient/parent agrees to participate in the study, the research&#xD;
      team member will consent the parents of the patients aged 0-17 years or consent patients aged&#xD;
      18 years. Assent will be obtained from patients aged 8-17 years. Non-English speaking&#xD;
      patients/parents will be consented using an in-person translator or the blue phone&#xD;
      translating service. These consent and assent forms will be signed by a witness. At the time&#xD;
      of enrollment, the subject identification (ID) number and medical record number will be&#xD;
      entered into the electronic Subject ID Key. Once the patient is enrolled in the study, their&#xD;
      treatment will be randomized to either the LR or the NS group. Both treatments are current&#xD;
      standard of care for acute pancreatitis. Patients who choose not to participate in the study&#xD;
      will receive the standard of care treatment at the discretion of the attending physician,&#xD;
      which may involve either fluid, and will likely include most (if not all) of the lab studies&#xD;
      as outlined in this protocol.&#xD;
&#xD;
      The goal is to screen and enroll the subjects in either the ED or inpatient ward within 6&#xD;
      hours of diagnosis, as this is within the theoretical window prior to the development of&#xD;
      systemic inflammation. At the discretion of the attending physician, however, treatment can&#xD;
      begin in the ED or inpatient ward before enrollment in the study; patients will not have to&#xD;
      wait for necessary treatments. Patients will still be eligible to participate in the study if&#xD;
      treatment was begun in the ED or inpatient ward. The randomized treatment may end up being&#xD;
      the same or different than what was originally ordered by the attending physician. If any&#xD;
      such changes in treatment plan are noted, this will be considered for the data analysis.&#xD;
&#xD;
      The randomization plan will include constrained randomization using the permuted blocks&#xD;
      method. The research team member will open the envelope that contains the randomized&#xD;
      treatment and the Admission Order Sheet that details the orders that need to be placed on&#xD;
      admission. The research team member will communicate this information to the ED or inpatient&#xD;
      attending physician or staff member overseeing the patient's care at the time of enrollment.&#xD;
      All clinical treatments described in this protocol, including labs orders, are the current&#xD;
      standard of care for acute pancreatitis diagnosis. The purpose of the Admission Order Sheet&#xD;
      is to standardize the timeline of the lab work at admission, at 24 hours and 48 hours after&#xD;
      admission, not to request any additional lab work for the purposes of the study.&#xD;
&#xD;
      The subject will be placed on 1.5x maintenance IVF with the fluids to which they are&#xD;
      randomized. The patient will remain nil per os (NPO) for at least the first 24 hours, and the&#xD;
      time of initiating feeds after 24 hours will be at the discretion of the admitting team. As&#xD;
      the standard of care, the following studies will be obtained at the time of admission if not&#xD;
      previously obtained in the ED: Complete Metabolic Panel (CMP), gamma-glutamyltransferase&#xD;
      (GGT), Amylase, Lipase, Triglycerides, Complete Blood Count (CBC), and CRP, along with an&#xD;
      abdominal ultrasound. CBC, CRP, amylase and lipase levels will be obtained at 24 and 48 hours&#xD;
      (+/- 2 hours) as listed in the Admission Order Sheet. Similarly, a Basic Metabolic Panel&#xD;
      (BMP) will be collected at 24 and 48 hours (+/- 2 hours), with the addition of liver function&#xD;
      tests if liver enzyme levels are elevated at admission (as defined by transaminases greater&#xD;
      than 2 times the age appropriate upper limit of normal). SIRS status will be evaluated with&#xD;
      vital sign checks every 4 hours and the leukocyte counts every 24 hours.&#xD;
&#xD;
      The patients will be observed for additional known signs and complications of acute&#xD;
      pancreatitis such as persistent inflammation, shock, sepsis, electrolyte abnormalities, renal&#xD;
      failure or other end organ damage. Any adverse reactions during the trial will be treated&#xD;
      independent of the trial, and the attending physician will continue to manage the care of the&#xD;
      patient at their discretion. Any serious adverse reactions will be documented clinically and&#xD;
      reported to the CHKD or CNHS incident reporter systems, Eastern Virginia Medical School&#xD;
      (EVMS) Institutional Review Board (IRB), CNHS IRB and CHKD Human Research Coordination (HRC)&#xD;
      Committee .&#xD;
&#xD;
      The de-identified information will be collected from the patient's electronic medical record&#xD;
      by a research team member and entered directly into an Excel database. Patients transferred&#xD;
      from an outside ED should already have charts scanned into the Electronic Health Record (EHR)&#xD;
      as standard of care. If only a paper chart is available for any transferred patient, a&#xD;
      research team member will enter information directly from the paper chart into the Excel&#xD;
      database.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2014</start_date>
  <completion_date type="Actual">October 23, 2020</completion_date>
  <primary_completion_date type="Actual">October 23, 2020</primary_completion_date>
  <phase>N/A</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>C-Reactive Protein (CRP)</measure>
    <time_frame>At admission, 24 and 48 hours</time_frame>
    <description>Primary marker of inflammation, change measured at baseline and then every 24 hours for 48 hours</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Blood Urea Nitrogen (BUN)</measure>
    <time_frame>At admission, 24 and 48 hours</time_frame>
    <description>Trend BUN</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Amylase</measure>
    <time_frame>At admission, 24 and 48 hours</time_frame>
    <description>Trend Amylase over the course of the admission</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Lipase</measure>
    <time_frame>At admission, 24 and 48 hours</time_frame>
    <description>Trend Lipase over the course of the admission</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average length of stay</measure>
    <time_frame>Total length of stay in the hospital, measured in hours, usually around 4 days (96 hours).</time_frame>
    <description>Total length of stay in the hospital</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to initiation of enteral feeds</measure>
    <time_frame>Total length of time to initiate feeds in the hospital, measured in hours, usually around 2 days (48 hours).</time_frame>
    <description>Total time required to start oral feeds as defined by placement of order to start feeds</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SIRS Criteria</measure>
    <time_frame>At admission, 24 and 48 hours</time_frame>
    <description>Signs of Systemic Inflammatory Response Syndrome (SIRS) as defined by Goldstein et al will be compared.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">79</enrollment>
  <condition>Pancreatitis</condition>
  <arm_group>
    <arm_group_label>Lactated Ringers (LR)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The subject will be placed on 1.5x maintenance IVF with the fluids to which they are randomized. Fluid Management will be the intervention.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Normal Saline (NS)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The subject will be placed on 1.5x maintenance IVF with the fluids to which they are randomized. Fluid Management will be the intervention.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Fluid Management</intervention_name>
    <description>The patient will remain NPO for at least the first 24 hours. The following studies will be obtained at the time of admission if not previously obtained in the ED: CMP, GGT, Amylase, Lipase, Triglycerides, CBC, and CRP, along with an abdominal ultrasound. CBC, CRP, BMP, amylase and lipase levels will be obtained at 24 and 48 hours (+/- 2 hours). SIRS status will be evaluated with vital sign checks every 4 hours and the leukocyte counts every 24 hours.</description>
    <arm_group_label>Lactated Ringers (LR)</arm_group_label>
    <arm_group_label>Normal Saline (NS)</arm_group_label>
    <other_name>Resuscitative fluids for acute pancreatitis</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients aged 0-18 years diagnosed with acute pancreatitis in the emergency department&#xD;
             or inpatient ward at Children's Hospital of The King's Daughters or one of the&#xD;
             affiliated institutions participating in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients greater than 18 years of age&#xD;
&#xD;
          -  Patients who are not diagnosed with acute pancreatitis&#xD;
&#xD;
          -  Patients who have any previous history of acute pancreatitis, past medical history of&#xD;
             underlying illness including congenital heart disease, chronic lung disease, or renal&#xD;
             failure&#xD;
&#xD;
          -  Patients who have any of the following: hyperkalemia, systemic acidosis, acute&#xD;
             dehydration, extensive tissue breakdown, adrenal insufficiency, concomitant use of&#xD;
             potassium-sparing diuretics, use of extended-release preparations in patients with&#xD;
             esophageal compression caused by an enlarged left atrium, hypersensitivity to sodium&#xD;
             chloride, hypernatremia, or fluid retention&#xD;
&#xD;
          -  Patients who are pregnant females&#xD;
&#xD;
          -  Patients who have additional comorbidities at time of admission that would prevent&#xD;
             adequate treatment with the methods described above will be excluded&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>0 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Peter R Farrell, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital Medical Center, Cincinnati</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sona Sehgal, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's National Health System</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rana Ammoury, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital of The King's Daughters</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Maisam Abu-El-Haija, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital Medical Center, Cincinnati</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's National Health System</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of The King's Daughters</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23507</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Srinath AI, Lowe ME. Pediatric pancreatitis. Pediatr Rev. 2013 Feb;34(2):79-90. doi: 10.1542/pir.34-2-79. No abstract available.</citation>
    <PMID>23378615</PMID>
  </reference>
  <reference>
    <citation>Sarr MG. Early fluid &quot;resuscitation/therapy&quot; in acute pancreatitis: which fluid? What rate? What parameters to gauge effectiveness? Ann Surg. 2013 Feb;257(2):189-90. doi: 10.1097/SLA.0b013e318280e19e. No abstract available.</citation>
    <PMID>23291660</PMID>
  </reference>
  <reference>
    <citation>Meyer A, Coffey MJ, Oliver MR, Ooi CY. Contrasts and comparisons between childhood and adult onset acute pancreatitis. Pancreatology. 2013 Jul-Aug;13(4):429-35. doi: 10.1016/j.pan.2013.06.005. Epub 2013 Jun 27.</citation>
    <PMID>23890143</PMID>
  </reference>
  <reference>
    <citation>Wu BU, Hwang JQ, Gardner TH, Repas K, Delee R, Yu S, Smith B, Banks PA, Conwell DL. Lactated Ringer's solution reduces systemic inflammation compared with saline in patients with acute pancreatitis. Clin Gastroenterol Hepatol. 2011 Aug;9(8):710-717.e1. doi: 10.1016/j.cgh.2011.04.026. Epub 2011 May 12.</citation>
    <PMID>21645639</PMID>
  </reference>
  <reference>
    <citation>Goldstein B, Giroir B, Randolph A; International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. 2005 Jan;6(1):2-8. doi: 10.1097/01.PCC.0000149131.72248.E6.</citation>
    <PMID>15636651</PMID>
  </reference>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>August 22, 2016</study_first_submitted>
  <study_first_submitted_qc>August 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 8, 2017</study_first_posted>
  <last_update_submitted>August 11, 2021</last_update_submitted>
  <last_update_submitted_qc>August 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 17, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Children's Hospital Medical Center, Cincinnati</investigator_affiliation>
    <investigator_full_name>Peter Farrell</investigator_full_name>
    <investigator_title>Clinical Fellow, Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pancreatitis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>We plan to share the de-identified data obtained at CCHMC with our partners at CHKD and Children's National Medical Center, and we intend to have them share their data with us as well.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Data will be shared for up to 3 years after the conclusion of recruitment.</ipd_time_frame>
  </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/NCT03242473
org study id: 14-12-FB-0245
nct id: NCT03242473
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
Acute pancreatitis is increasingly common diagnosis in children. Most of the guidelines
      related to the details of management of acute pancreatitis are extrapolated from the adult
      literature. There is only limited data regarding management of acute pancreatitis in
      children. The mainstay of management is bowel and pancreatic rest with significant fluid
      support to minimize the effect of the cytokines on the pancreas and other organs. The
      standard fluid choices are Lactated Ringer's solution (LR) and normal saline (NS). Currently,
      both LR and NS are used at the discretion of the treating physician as the standard of care
      for acute pancreatitis. The investigators hope to examine the question of ideal fluid choice
      for fluid resuscitation in children with acute pancreatitis by assessing recovery time in the
      context of measured inflammatory markers and SIRS status at 24 and 48 hours after admission.
      The ideal fluid choice in the initial resuscitation of acute pancreatitis has not been
      effectively evaluated before in the pediatric population. Even if there is no statistically
      significant difference between the two fluid options, this trial will still provide
      clinically significant information.
Acute pancreatitis represents inflammation of the pancreas that has been well identified in
      the literature for several centuries. However, the phenomenon has only relatively recently
      gained prominence in the pediatric literature. The incidence can be as high as 13 per 100,000
      per year, a level which approaches that seen in adults, and the diagnosis has been
      increasingly common over the last two decades. It affects all ages of children (including
      infants) evidenced by well-established age appropriate diagnostic criteria. The precise
      pathophysiological basis of the inflammation is not always as clear. Currently, the
      prevailing theory is that there is an insult to the acinar cells of the pancreas likely via
      an atypical calcium signal that releases a cascade of cellular activity and that ultimately
      results in a disseminated cytokine storm. While there is certainly debate as to the inciting
      event to this cascade, one thing that is clear is that extensive end-organ damage can occur
      if this cytokine storm reaches systemic circulation. Therefore, the mainstay of management is
      bowel (and specifically pancreatic) rest with significant fluid support to minimize or
      mitigate the effect of the cytokines on the pancreas and other systemic organs such as the
      lungs, heart, and kidneys. The remainder of therapy consists of appropriate analgesia and
      antiemetics.

      Unfortunately, most of the guidelines related to the details of management of acute
      pancreatitis are extrapolated from the adult literature. There is only limited data regarding
      management of acute pancreatitis in children. Recently, Wu et al. have shown compelling data
      that suggest the choice of fluid for management of acute pancreatitis in adults should be
      Lactated Ringers (LR). Their group demonstrated in a small randomized controlled trial
      involving 40 adult patients with acute pancreatitis, that the patients randomized to the LR
      arm of the study had significantly lower levels of C-reactive protein and Systemic
      Inflammatory Response Syndrome (SIRS) markers compared with controls in the normal saline
      (NS) group. They proposed that the mechanism for this difference may be related to the more
      balanced pH of LR which might prevent, or at least further buffer, the systemic inflammation
      that is triggered by the release of the offending cytokines from the pancreas. Currently,
      both LR and NS are used at both Children's Hospital of The King's Daughters (CHKD) and
      Children's National Health System (CNHS) at the discretion of the attending physician as the
      standard of care for acute pancreatitis. The investigators hope to examine the question of
      ideal fluid choice for fluid resuscitation in children with acute pancreatitis by assessing
      recovery time in the context of measured inflammatory markers and SIRS status at 24 and 48
      hours after admission.

      This is a prospective randomized trial of pediatric patients in the emergency department (ED)
      or inpatient ward diagnosed with acute pancreatitis. Patients meeting the study inclusion
      criteria will be identified by an ED or inpatient physician. The ED or inpatient physician
      will ask the eligible patient/parent if they are interested in hearing about the study. If
      the eligible patient/parent is interested in hearing information about the study, the ED or
      inpatient ward will notify the PI via telephone or page. The PI will come to the eligible
      patient's room to explain the study and answer any questions, or the PI will page a research
      team member to do so. If the patient/parent agrees to participate in the study, the research
      team member will consent the parents of the patients aged 0-17 years or consent patients aged
      18 years. Assent will be obtained from patients aged 8-17 years. Non-English speaking
      patients/parents will be consented using an in-person translator or the blue phone
      translating service. These consent and assent forms will be signed by a witness. At the time
      of enrollment, the subject identification (ID) number and medical record number will be
      entered into the electronic Subject ID Key. Once the patient is enrolled in the study, their
      treatment will be randomized to either the LR or the NS group. Both treatments are current
      standard of care for acute pancreatitis. Patients who choose not to participate in the study
      will receive the standard of care treatment at the discretion of the attending physician,
      which may involve either fluid, and will likely include most (if not all) of the lab studies
      as outlined in this protocol.

      The goal is to screen and enroll the subjects in either the ED or inpatient ward within 6
      hours of diagnosis, as this is within the theoretical window prior to the development of
      systemic inflammation. At the discretion of the attending physician, however, treatment can
      begin in the ED or inpatient ward before enrollment in the study; patients will not have to
      wait for necessary treatments. Patients will still be eligible to participate in the study if
      treatment was begun in the ED or inpatient ward. The randomized treatment may end up being
      the same or different than what was originally ordered by the attending physician. If any
      such changes in treatment plan are noted, this will be considered for the data analysis.

      The randomization plan will include constrained randomization using the permuted blocks
      method. The research team member will open the envelope that contains the randomized
      treatment and the Admission Order Sheet that details the orders that need to be placed on
      admission. The research team member will communicate this information to the ED or inpatient
      attending physician or staff member overseeing the patient's care at the time of enrollment.
      All clinical treatments described in this protocol, including labs orders, are the current
      standard of care for acute pancreatitis diagnosis. The purpose of the Admission Order Sheet
      is to standardize the timeline of the lab work at admission, at 24 hours and 48 hours after
      admission, not to request any additional lab work for the purposes of the study.

      The subject will be placed on 1.5x maintenance IVF with the fluids to which they are
      randomized. The patient will remain nil per os (NPO) for at least the first 24 hours, and the
      time of initiating feeds after 24 hours will be at the discretion of the admitting team. As
      the standard of care, the following studies will be obtained at the time of admission if not
      previously obtained in the ED: Complete Metabolic Panel (CMP), gamma-glutamyltransferase
      (GGT), Amylase, Lipase, Triglycerides, Complete Blood Count (CBC), and CRP, along with an
      abdominal ultrasound. CBC, CRP, amylase and lipase levels will be obtained at 24 and 48 hours
      (+/- 2 hours) as listed in the Admission Order Sheet. Similarly, a Basic Metabolic Panel
      (BMP) will be collected at 24 and 48 hours (+/- 2 hours), with the addition of liver function
      tests if liver enzyme levels are elevated at admission (as defined by transaminases greater
      than 2 times the age appropriate upper limit of normal). SIRS status will be evaluated with
      vital sign checks every 4 hours and the leukocyte counts every 24 hours.

      The patients will be observed for additional known signs and complications of acute
      pancreatitis such as persistent inflammation, shock, sepsis, electrolyte abnormalities, renal
      failure or other end organ damage. Any adverse reactions during the trial will be treated
      independent of the trial, and the attending physician will continue to manage the care of the
      patient at their discretion. Any serious adverse reactions will be documented clinically and
      reported to the CHKD or CNHS incident reporter systems, Eastern Virginia Medical School
      (EVMS) Institutional Review Board (IRB), CNHS IRB and CHKD Human Research Coordination (HRC)
      Committee .

      The de-identified information will be collected from the patient's electronic medical record
      by a research team member and entered directly into an Excel database. Patients transferred
      from an outside ED should already have charts scanned into the Electronic Health Record (EHR)
      as standard of care. If only a paper chart is available for any transferred patient, a
      research team member will enter information directly from the paper chart into the Excel
      database.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: C-Reactive Protein (CRP)
time frame: At admission, 24 and 48 hours
description: Primary marker of inflammation, change measured at baseline and then every 24 hours for 48 hours
measure: Blood Urea Nitrogen (BUN)
time frame: At admission, 24 and 48 hours
description: Trend BUN
measure: Serum Amylase
time frame: At admission, 24 and 48 hours
description: Trend Amylase over the course of the admission
measure: Serum Lipase
time frame: At admission, 24 and 48 hours
description: Trend Lipase over the course of the admission
measure: Average length of stay
time frame: Total length of stay in the hospital, measured in hours, usually around 4 days (96 hours).
description: Total length of stay in the hospital
measure: Time to initiation of enteral feeds
time frame: Total length of time to initiate feeds in the hospital, measured in hours, usually around 2 days (48 hours).
description: Total time required to start oral feeds as defined by placement of order to start feeds
measure: SIRS Criteria
time frame: At admission, 24 and 48 hours
description: Signs of Systemic Inflammatory Response Syndrome (SIRS) as defined by Goldstein et al will be compared.
arm group label: Lactated Ringers (LR)
arm group type: Experimental
description: The subject will be placed on 1.5x maintenance IVF with the fluids to which they are randomized. Fluid Management will be the intervention.
arm group label: Normal Saline (NS)
arm group type: Experimental
description: The subject will be placed on 1.5x maintenance IVF with the fluids to which they are randomized. Fluid Management will be the intervention.
intervention type: Other
intervention name: Fluid Management
description: The patient will remain NPO for at least the first 24 hours. The following studies will be obtained at the time of admission if not previously obtained in the ED: CMP, GGT, Amylase, Lipase, Triglycerides, CBC, and CRP, along with an abdominal ultrasound. CBC, CRP, BMP, amylase and lipase levels will be obtained at 24 and 48 hours (+/- 2 hours). SIRS status will be evaluated with vital sign checks every 4 hours and the leukocyte counts every 24 hours.
arm group label: Lactated Ringers (LR)
arm group label: Normal Saline (NS)
other name: Resuscitative fluids for acute pancreatitis
criteria: 
gender: All
minimum age: 0 Years
maximum age: 18 Years
healthy volunteers: No
last name: Peter R Farrell, MD
role: Principal Investigator
affiliation: Children's Hospital Medical Center, Cincinnati
last name: Sona Sehgal, MD
role: Principal Investigator
affiliation: Children's National Health System
last name: Rana Ammoury, MD
role: Principal Investigator
affiliation: Children's Hospital of The King's Daughters
last name: Maisam Abu-El-Haija, MD
role: Principal Investigator
affiliation: Children's Hospital Medical Center, Cincinnati
facility: 
facility: 
facility: 
country: United States
citation: Srinath AI, Lowe ME. Pediatric pancreatitis. Pediatr Rev. 2013 Feb;34(2):79-90. doi: 10.1542/pir.34-2-79. No abstract available.
PMID: 23378615
citation: Sarr MG. Early fluid "resuscitation/therapy" in acute pancreatitis: which fluid? What rate? What parameters to gauge effectiveness? Ann Surg. 2013 Feb;257(2):189-90. doi: 10.1097/SLA.0b013e318280e19e. No abstract available.
PMID: 23291660
citation: Meyer A, Coffey MJ, Oliver MR, Ooi CY. Contrasts and comparisons between childhood and adult onset acute pancreatitis. Pancreatology. 2013 Jul-Aug;13(4):429-35. doi: 10.1016/j.pan.2013.06.005. Epub 2013 Jun 27.
PMID: 23890143
citation: Wu BU, Hwang JQ, Gardner TH, Repas K, Delee R, Yu S, Smith B, Banks PA, Conwell DL. Lactated Ringer's solution reduces systemic inflammation compared with saline in patients with acute pancreatitis. Clin Gastroenterol Hepatol. 2011 Aug;9(8):710-717.e1. doi: 10.1016/j.cgh.2011.04.026. Epub 2011 May 12.
PMID: 21645639
citation: Goldstein B, Giroir B, Randolph A; International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. 2005 Jan;6(1):2-8. doi: 10.1097/01.PCC.0000149131.72248.E6.
PMID: 15636651
responsible party type: Principal Investigator
investigator affiliation: Children's Hospital Medical Center, Cincinnati
investigator full name: Peter Farrell
investigator title: Clinical Fellow, Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition
mesh term: Pancreatitis
sharing ipd: Yes
ipd description: We plan to share the de-identified data obtained at CCHMC with our partners at CHKD and Children's National Medical Center, and we intend to have them share their data with us as well.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Data will be shared for up to 3 years after the conclusion of recruitment.