<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/NCT03020875</url>
  </required_header>
  <id_info>
    <org_study_id>2015-516</org_study_id>
    <nct_id>NCT03020875</nct_id>
  </id_info>
  <brief_title>IV vs Oral Acetaminophen in Spine Fusion Perioperative Care</brief_title>
  <official_title>Single-Center, Randomized Controlled Trial of Intravenous v Oral Acetaminophen Administration in Perioperative Care of 1 and 2 Level XLIFs Supplemented With Bilateral Pedicle Screw Stabilization: a Comparative Effectiveness Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital for Special Surgery, New York</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Mallinckrodt</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Hospital for Special Surgery, New York</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The United States is currently experiencing an explosive opioid epidemic. In 2014 alone,&#xD;
      28,647 Americans died from an opioid associated overdose; the annual death toll has increased&#xD;
      by over 300% since 2000. The epidemic poses a complex scenario for physicians administering&#xD;
      treatment for postoperative pain, as opioids are key analgesic agents in treating moderate to&#xD;
      severe pain. In order to reduce the patients risk for long term opioid use and the associated&#xD;
      side effects, physicians have begun shifting to multimodal analgesic approaches to treat&#xD;
      postoperative pain. These approaches have been found to be similarly efficacious, while also&#xD;
      reducing opioid usage and associated side effects, such as: nausea, vomiting, and ileus.&#xD;
&#xD;
      This study proposes a multimodal analgesic approach, which the investigators believe will&#xD;
      reduce short and long term opioid usage, the associated side effects, and the financial&#xD;
      burden. Intravenous acetaminophen is an effective medication for both primary and adjunctive&#xD;
      pain management, however its use is limited by a high cost to perceived benefit ratio. Oral&#xD;
      acetaminophen is a relatively inexpensive option, although perhaps less effective than the IV&#xD;
      option, and also often not feasible to utilize in the immediate post-operative period when&#xD;
      patients are unable to safely swallow pills. The hypothesis of this investigation is to&#xD;
      understand if adding intravenous acetaminophen to the perioperative care regimen after lumbar&#xD;
      spinal surgery will result in improved pain management in the perioperative period while&#xD;
      decreasing opioid usage and related complications.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date>January 2017</start_date>
  <completion_date type="Anticipated">March 2024</completion_date>
  <primary_completion_date type="Anticipated">March 2024</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>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Visual Analog Scale (VAS) for back and legs</measure>
    <time_frame>Change from baseline VAS at 6 months postoperative</time_frame>
    <description>Self reported pain frequency and intensity at 24 hour postoperative intervals until patient is discharged, at 6 week and 6 month follow-up. The scale is scored on a 100 mm line, with 0 being no pain and 100 being worst pain imaginable.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Length of Stay (LOS)</measure>
    <time_frame>Immediate postoperative</time_frame>
    <description>Measured in total hours until discharge from hospital</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Opioid Equivalent Dosing during Hospital Stay</measure>
    <time_frame>Postoperative</time_frame>
    <description>Measured every 24 hours postoperative until discharge from hospital</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Ambulation</measure>
    <time_frame>Immediate postoperative</time_frame>
    <description>Measured in total hours postoperative until patient is ambulatory</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oswestry Disability Index Version 2.1 (ODI)</measure>
    <time_frame>Preoperative, 6 weeks and 6 months postoperative</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long Term Opioid Usage</measure>
    <time_frame>6 months Postoperative</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">166</enrollment>
  <condition>Multimodal Analgesic Approach</condition>
  <arm_group>
    <arm_group_label>PO Acetaminophen</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Preop:&#xD;
Eligible patients will receive oral acetaminophen within 3 hours of OR start time.&#xD;
Postop:&#xD;
Eligible patients will be administered oral acetaminophen following 1 and 2 level LLIFs supplemented with instrumented posterior fusion to evaluate pain management outcomes. Dosing for the group will be the following:&#xD;
• Oral Acetaminophen 1,000 mg every 6 hours for 48 hours postoperative. Medication will be given at least 6 hours following initial preoperative dose of oral acetaminophen.&#xD;
Postop supplemental pain medications:&#xD;
All patients will receive a standardized hydromorphone IV-PCA order set for 24 hours postoperatively. The use of tramadol and tapentadol will specifically be discouraged due to challenges in determining morphine-equivalent dosing with these specific agents. Similarly, acetaminophen containing combination products (e.g. oxycodone/acetaminophen or hydrocodone/acetaminophen) will not be allowed due to overlap with the primary study medications.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intravenous Acetaminophen</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Preop:&#xD;
Eligible patients will receive IV acetaminophen within 3 hours of OR start time.&#xD;
Postop:&#xD;
Eligible patients will be administered IV acetaminophen following 1 and 2 level LLIFs supplemented with instrumented posterior fusion to evaluate pain management outcomes. Dosing for the group will be the following:&#xD;
• IV Acetaminophen 1,000 mg [100 ml] every 6 hours for 48 hours postoperative. Medication will be given at least 6 hours following initial preoperative dose of IV acetaminophen.&#xD;
Postop supplemental pain medications:&#xD;
All patients will receive a standardized hydromorphone IV-PCA order set for 24 hours postoperatively. The use of tramadol and tapentadol will specifically be discouraged due to challenges in determining morphine-equivalent dosing with these specific agents. Similarly, acetaminophen containing combination products (e.g. oxycodone/acetaminophen or hydrocodone/acetaminophen) will not be allowed due to overlap with the primary study medications.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ofirmev</intervention_name>
    <description>Intravenously administered acetaminophen.</description>
    <arm_group_label>Intravenous Acetaminophen</arm_group_label>
    <other_name>Intravenous Acetaminophen</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Per Os Acetaminophen</intervention_name>
    <description>Orally administered acetaminophen.</description>
    <arm_group_label>PO Acetaminophen</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of spinal stenosis of the lumbar spine with degenerative spondylolisthesis&#xD;
&#xD;
          -  Skeletally mature adults between the ages of 18-85 years at the time of surgery&#xD;
&#xD;
          -  The greater of the patients right and left VAS leg pain, or back pain, score is &gt; 40&#xD;
             mm on a 100 mm scale&#xD;
&#xD;
          -  Has attempted conservative therapy&#xD;
&#xD;
          -  Psychosocially, mentally, and physically able to fully comply with this protocol,&#xD;
             including adhering to scheduled visits, treatment plan, completing forms, and other&#xD;
             study procedures&#xD;
&#xD;
          -  Personally signed and dated informed consent document prior to any study-related&#xD;
             procedures indicating that the patient has been informed of all pertinent aspects of&#xD;
             the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any evidence of a prior/current fracture, compromised vertebra, current or past&#xD;
             trauma, or tumor at affected level or the spinous processes at the adjacent levels&#xD;
&#xD;
          -  Revision of prior fusion attempt at the level being operated on&#xD;
&#xD;
          -  Cauda Equina Syndrome defined as neural compression causing neurogenic bowel (rectal&#xD;
             incontinence) or bladder dysfunction (bladder retention or incontinence)&#xD;
&#xD;
          -  Significant peripheral neuropathy or acute denervation secondary to radiculopathy,&#xD;
             caused by conditions other than spinal stenosis&#xD;
&#xD;
          -  Significant peripheral vascular disease (diminished dornails pedis or tibial pulses)&#xD;
&#xD;
          -  Morbid obesity, defined as BMI &gt; 40 kg/m2; or underweight, defined as BMI &lt; 18.5 kg/m2&#xD;
&#xD;
          -  Active systematic or local infection&#xD;
&#xD;
          -  Active Viral Hepatitis (receiving medical treatment within 1 year); or any other acute&#xD;
             hepatitis within the past 6 months&#xD;
&#xD;
          -  Immunocompromised such as but not limited to Acquired Immunodeficiency Syndrome&#xD;
             (AIDS), HIV infection, Severe Combined Immunodeficiency Syndrome, Thymic Hypoplasia&#xD;
&#xD;
          -  Insulin dependent diabetes mellitus or any other medical conditions that would&#xD;
             represent a significant increase in surgical risk or interfere with normal healing&#xD;
&#xD;
          -  Immunologically suppressed, or has received systemic steroids, excluding nasal&#xD;
             steroids, at any dose for &gt;1 month within last 12 months&#xD;
&#xD;
          -  History of Paget's disease, osteomalacia, or osteoporosis with a DEXA t-score less&#xD;
             than or equal to -2.5&#xD;
&#xD;
          -  Active malignancy. A patient with a history of any invasive malignancy (except&#xD;
             non-melanoma skin cancer), unless treated with curative intent and there has been no&#xD;
             clinical signs or symptoms of the malignancy &gt;5 years&#xD;
&#xD;
          -  Any current history of substance abuse (e.g., recreational drugs, narcotics, or&#xD;
             alcohol)&#xD;
&#xD;
          -  History of psychosocial disorders that could prevent accurate completion of&#xD;
             self-reporting assessment scales&#xD;
&#xD;
          -  Previous known allergy to acetaminophen&#xD;
&#xD;
          -  Women who are pregnant or lactating&#xD;
&#xD;
          -  Patients involved in active litigation relating to his/her spinal condition&#xD;
&#xD;
          -  Patients taking &gt;30mg/day of oral morphine sulfate, or the equivalent of this daily&#xD;
             for more than 3 months&#xD;
&#xD;
          -  Patient is unable to ingest orally administered medication&#xD;
&#xD;
          -  Patient receiving autologous Iliac Crest bone graft (ICBG)&#xD;
&#xD;
          -  Known intolerance of or true allergy to hydromorphone or oxycodone.&#xD;
&#xD;
          -  History of moderate to severe Cirrhosis, defined as Child Pugh score of class B, C, or&#xD;
             D&#xD;
&#xD;
          -  History of Hemochromatosis or Porphyria&#xD;
&#xD;
          -  Patient taking Isoniazid or barbiturates&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chad Craig, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital for Special Surgery, New York</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital for Special Surgery</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>July 5, 2016</study_first_submitted>
  <study_first_submitted_qc>January 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 13, 2017</study_first_posted>
  <last_update_submitted>March 29, 2023</last_update_submitted>
  <last_update_submitted_qc>March 29, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 31, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Acetaminophen</keyword>
  <keyword>Pain management</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetaminophen</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/NCT03020875
org study id: 2015-516
nct id: NCT03020875
lead sponsor: 
collaborator: 
has dmc: Yes
The United States is currently experiencing an explosive opioid epidemic. In 2014 alone,
      28,647 Americans died from an opioid associated overdose; the annual death toll has increased
      by over 300% since 2000. The epidemic poses a complex scenario for physicians administering
      treatment for postoperative pain, as opioids are key analgesic agents in treating moderate to
      severe pain. In order to reduce the patients risk for long term opioid use and the associated
      side effects, physicians have begun shifting to multimodal analgesic approaches to treat
      postoperative pain. These approaches have been found to be similarly efficacious, while also
      reducing opioid usage and associated side effects, such as: nausea, vomiting, and ileus.

      This study proposes a multimodal analgesic approach, which the investigators believe will
      reduce short and long term opioid usage, the associated side effects, and the financial
      burden. Intravenous acetaminophen is an effective medication for both primary and adjunctive
      pain management, however its use is limited by a high cost to perceived benefit ratio. Oral
      acetaminophen is a relatively inexpensive option, although perhaps less effective than the IV
      option, and also often not feasible to utilize in the immediate post-operative period when
      patients are unable to safely swallow pills. The hypothesis of this investigation is to
      understand if adding intravenous acetaminophen to the perioperative care regimen after lumbar
      spinal surgery will result in improved pain management in the perioperative period while
      decreasing opioid usage and related complications.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Investigator)
measure: Visual Analog Scale (VAS) for back and legs
time frame: Change from baseline VAS at 6 months postoperative
description: Self reported pain frequency and intensity at 24 hour postoperative intervals until patient is discharged, at 6 week and 6 month follow-up. The scale is scored on a 100 mm line, with 0 being no pain and 100 being worst pain imaginable.
measure: Length of Stay (LOS)
time frame: Immediate postoperative
description: Measured in total hours until discharge from hospital
measure: Opioid Equivalent Dosing during Hospital Stay
time frame: Postoperative
description: Measured every 24 hours postoperative until discharge from hospital
measure: Time to Ambulation
time frame: Immediate postoperative
description: Measured in total hours postoperative until patient is ambulatory
measure: Oswestry Disability Index Version 2.1 (ODI)
time frame: Preoperative, 6 weeks and 6 months postoperative
measure: Long Term Opioid Usage
time frame: 6 months Postoperative
arm group label: PO Acetaminophen
arm group type: Active Comparator
description: Preop:
Eligible patients will receive oral acetaminophen within 3 hours of OR start time.
Postop:
Eligible patients will be administered oral acetaminophen following 1 and 2 level LLIFs supplemented with instrumented posterior fusion to evaluate pain management outcomes. Dosing for the group will be the following:
• Oral Acetaminophen 1,000 mg every 6 hours for 48 hours postoperative. Medication will be given at least 6 hours following initial preoperative dose of oral acetaminophen.
Postop supplemental pain medications:
All patients will receive a standardized hydromorphone IV-PCA order set for 24 hours postoperatively. The use of tramadol and tapentadol will specifically be discouraged due to challenges in determining morphine-equivalent dosing with these specific agents. Similarly, acetaminophen containing combination products (e.g. oxycodone/acetaminophen or hydrocodone/acetaminophen) will not be allowed due to overlap with the primary study medications.
arm group label: Intravenous Acetaminophen
arm group type: Active Comparator
description: Preop:
Eligible patients will receive IV acetaminophen within 3 hours of OR start time.
Postop:
Eligible patients will be administered IV acetaminophen following 1 and 2 level LLIFs supplemented with instrumented posterior fusion to evaluate pain management outcomes. Dosing for the group will be the following:
• IV Acetaminophen 1,000 mg [100 ml] every 6 hours for 48 hours postoperative. Medication will be given at least 6 hours following initial preoperative dose of IV acetaminophen.
Postop supplemental pain medications:
All patients will receive a standardized hydromorphone IV-PCA order set for 24 hours postoperatively. The use of tramadol and tapentadol will specifically be discouraged due to challenges in determining morphine-equivalent dosing with these specific agents. Similarly, acetaminophen containing combination products (e.g. oxycodone/acetaminophen or hydrocodone/acetaminophen) will not be allowed due to overlap with the primary study medications.
intervention type: Drug
intervention name: Ofirmev
description: Intravenously administered acetaminophen.
arm group label: Intravenous Acetaminophen
other name: Intravenous Acetaminophen
intervention type: Drug
intervention name: Per Os Acetaminophen
description: Orally administered acetaminophen.
arm group label: PO Acetaminophen
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Chad Craig, MD
role: Principal Investigator
affiliation: Hospital for Special Surgery, New York
facility: 
country: United States
responsible party type: Sponsor
mesh term: Acetaminophen
sharing ipd: Undecided