<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/NCT03021083</url>
  </required_header>
  <id_info>
    <org_study_id>2016-803</org_study_id>
    <nct_id>NCT03021083</nct_id>
  </id_info>
  <brief_title>IONSYS Feasibility Study</brief_title>
  <acronym>IONSYS Pilot</acronym>
  <official_title>Evaluating the Feasibility of Using Transdermal Patient-controlled Fentanyl After Spinal Fusions</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital for Special Surgery, New York</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Medicines Company</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Hospital for Special Surgery, New York</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The treatment of postoperative pain continues to be a challenge after posterior spinal&#xD;
      fusions. There is considerable evidence demonstrating that a multi-modality approach&#xD;
      including patient controlled analgesia (PCA) with opioids for postoperative pain management&#xD;
      compared to conventional opioid analgesia provides a greater analgesic effect even when the&#xD;
      amount of opioids consumed is similar between both groups. However, the PCA modality is often&#xD;
      discontinued prior to all the patients' pain needs being met. The IONSYS system uses the&#xD;
      concept of PCA-delivered narcotics and may be used for postoperative pain management.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Following posterior spinal fusions, many patients are treated with analgesics or other&#xD;
      modalities for prolonged periods before choosing the surgical alternative. In addition, the&#xD;
      narcotic-based anesthetic required for the procedure may induce postoperative hyperalgesia&#xD;
      (1). Inadequate treatment of this pain can result in prolonged hospitalization,&#xD;
      cardiopulmonary complications, and poor surgical outcome (2).&#xD;
&#xD;
      Pain during the immediate postoperative period is usually managed with IV narcotic PCA and&#xD;
      then transitioned to a combination of long-acting and short-acting oral analgesics. Because&#xD;
      of the requirement for continuous carrier fluid infusion, cumbersome pump technology&#xD;
      restricting mobility and supervision by a dedicated pain team to control programming of the&#xD;
      pump, the PCA modality is often discontinued prior to all the patients' pain needs being met.&#xD;
&#xD;
      The investigators' most recent study evaluated the addition of pregabalin to the pain regimen&#xD;
      after spinal fusions. The study found that after the removal of the PCA modality, these&#xD;
      patients had considerable pain during physical therapy (PT), and their pain was not improved&#xD;
      with the addition of pregabalin.&#xD;
&#xD;
      The IONSYS system might alleviate some of the problems encountered with conventional PCA&#xD;
      systems (3,4). The system is an iontophoretic transdermal (needleless) system preprogrammed&#xD;
      to deliver upon activation 40 mcg fentanyl over a 10-minute period, with up to 6 doses per&#xD;
      hour. The system performs for 24 hours. The drug is embedded in a matrix gel and is only&#xD;
      delivered when a current is propagated between the two poles of the system. Other than the&#xD;
      usual narcotic side effects, the only specific side effect is a local dermatological reaction&#xD;
      to the patch (5% had a rash, which cleared after removal). The system was designed with&#xD;
      fentanyl, since hydromorphone cannot be incorporated in this type of matrix. Unlike&#xD;
      hydromorphone, fentanyl is quick acting and doesn't hang around. The in-house chronic pain&#xD;
      service currently puts many of their patients on IV fentanyl, because of the belief that it&#xD;
      works when they have pain but is quickly metabolized.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Contract not reached with sponsor&#xD;
  </why_stopped>
  <start_date type="Actual">November 1, 2017</start_date>
  <completion_date type="Actual">November 1, 2017</completion_date>
  <primary_completion_date type="Actual">November 1, 2017</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Feasibility of IONSYS system</measure>
    <time_frame>Day 2 following surgery for each patient</time_frame>
    <description>1. Nursing assessment regarding the ease of setup and initiation of the IONSYS system (With regard to setup and initiation of the IONSYS, on a scale of 0-10, where 0=worst and 10=best, how would the nurse rate the system?). This will be given to the nurse who sets up the device on DOS, and nurse who sets up the device on POD 1, and the day nurse on POD 2. An average score of 7 will be considered feasible.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>NRS Pain Scores</measure>
    <time_frame>Day 1 following surgery for each patient</time_frame>
    <description>1. NRS pain (0-10 scale) on first day after surgery (POD 1) during the afternoon session of PT. In a previous study on similar patients with IV PCA, we recorded mean pain scores of 4.6 during PT. Adequate pain control is delineated as NRS ≤ 3</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Day of eligibility for discharge,</measure>
    <time_frame>Up to 1 week after surgery</time_frame>
    <description>1. Day of eligibility for discharge, as assessed by a physical therapist's observation of a patient's ability to walk at least 20 feet and climb 4 stairs. Will be delineated as either AM or PM on a day following surgery, since PT is conducted twice daily.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>A Oswestry Back Pain Disability Index questionnaire</measure>
    <time_frame>6 weeks after surgery at the Post-Op Office Visit</time_frame>
    <description>An Oswestry Back Pain Disability Index questionnaire will be conducted at the first postoperative office visit to assess whether improved pain control in the hospital had an effect on the post-discharge recovery of the patient.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of Sedation</measure>
    <time_frame>POD1</time_frame>
    <description>Level of sedation, as assessed by PT starting on POD1 at the initiation of PT using the University of Michigan sedation scale: (1) awake and alert; (2) minimally sedated; (3) moderately sedated; (4) deeply sedated; (5) unarousable</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of Nausea of Vomiting</measure>
    <time_frame>POD1 and POD2 after surgery</time_frame>
    <description>Assess whether the patient has post-operative nausea and vomiting (PONV)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Satisfaction Survey</measure>
    <time_frame>Up to 1 week</time_frame>
    <description>A satisfaction survey will be conducted prior to discharge from the hospital. It will include the following questions: (1) Was the patient's pain adequately treated? (Y/N); (2) What was the patient's worst pain level after surgery? (0-10 scale); (3) Was the IONSYS device explained? (Y/N); (4) Did the patient have side effects to the IONSYS? (Y/N); (5) Was the patient able to perform PT? (Y/N); (6) Overall satisfaction with IONSYS device (0-10 scale; 0=not satisfied; 10=most satisfied).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Spinal Injury</condition>
  <arm_group>
    <arm_group_label>IONSYS Administration</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients who have elective multi-level spinal fusions under general anesthesia (who do not receive methadone) will be enrolled. In addition, all patients will receive Pepcid 20 mg, dexamethasone 10 mg, and ondansetron 4 mg.&#xD;
When patients will arrive in the post anesthesia care unit (PACU), pain will initially be controlled with IV hydromorphone to achieve an NRS score of 3 or less. Once transferred to the step down unit (SDU), the IONSYS patch will be applied. IONSYS should be utilized when they have pain, but rescue analgesia will be available. If severe pain continues, the chronic pain service will be consulted, to potentially change the medications.&#xD;
Patients will be assessed for pain at rest and with PT in the AM and PM of POD 1 and POD 2. The IONSYS system will be discontinued after 48 hours, and a total dose of fentanyl received per 24 hours will be recorded. PT milestones for discharge will be assessed on the afternoon of POD 1 and POD 2.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>IONSYS Patch</intervention_name>
    <description>Patient controlled transdermal fentanyl patch, IONSYS, applied to patient in place of a PCA.</description>
    <arm_group_label>IONSYS Administration</arm_group_label>
    <other_name>Patient Controlled Transdermal Fentanyl Patch</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients 18-70 years old undergoing elective multi-level lumbar-sacral posterior&#xD;
             spinal fusions&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Chronic pain patients taking more than 20-mg equivalents of oxycodone daily&#xD;
&#xD;
          -  Allergy to either hydromorphone or fentanyl&#xD;
&#xD;
          -  Other chronic orthopedic pain complaints, which will confound the results of the study&#xD;
&#xD;
          -  Issues with cognitive ability&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael Urban, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital for Special Surgery, New York</affiliation>
  </overall_official>
  <reference>
    <citation>Fletcher D, Martinez V. Opioid-induced hyperalgesia in patients after surgery: a systematic review and a meta-analysis. Br J Anaesth. 2014 Jun;112(6):991-1004. doi: 10.1093/bja/aeu137.</citation>
    <PMID>24829420</PMID>
  </reference>
  <reference>
    <citation>White PF. The changing role of non-opioid analgesic techniques in the management of postoperative pain. Anesth Analg. 2005 Nov;101(5 Suppl):S5-S22. doi: 10.1213/01.ANE.0000177099.28914.A7.</citation>
    <PMID>16334489</PMID>
  </reference>
  <reference>
    <citation>Scott LJ. Fentanyl Iontophoretic Transdermal System: A Review in Acute Postoperative Pain. Clin Drug Investig. 2016 Apr;36(4):321-30. doi: 10.1007/s40261-016-0387-x.</citation>
    <PMID>26968174</PMID>
  </reference>
  <reference>
    <citation>Mayes S, Ferrone M. Fentanyl HCl patient-controlled iontophoretic transdermal system for the management of acute postoperative pain. Ann Pharmacother. 2006 Dec;40(12):2178-86. doi: 10.1345/aph.1H135.</citation>
    <PMID>17164395</PMID>
  </reference>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>December 16, 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>April 12, 2022</last_update_submitted>
  <last_update_submitted_qc>April 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Lumbar multi-level fusions</keyword>
  <keyword>Patient Controlled Analgesia</keyword>
  <keyword>Fentanyl</keyword>
  <keyword>Opioid Analgesia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spinal Injuries</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fentanyl</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/NCT03021083
org study id: 2016-803
nct id: NCT03021083
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
The treatment of postoperative pain continues to be a challenge after posterior spinal
      fusions. There is considerable evidence demonstrating that a multi-modality approach
      including patient controlled analgesia (PCA) with opioids for postoperative pain management
      compared to conventional opioid analgesia provides a greater analgesic effect even when the
      amount of opioids consumed is similar between both groups. However, the PCA modality is often
      discontinued prior to all the patients' pain needs being met. The IONSYS system uses the
      concept of PCA-delivered narcotics and may be used for postoperative pain management.
Following posterior spinal fusions, many patients are treated with analgesics or other
      modalities for prolonged periods before choosing the surgical alternative. In addition, the
      narcotic-based anesthetic required for the procedure may induce postoperative hyperalgesia
      (1). Inadequate treatment of this pain can result in prolonged hospitalization,
      cardiopulmonary complications, and poor surgical outcome (2).

      Pain during the immediate postoperative period is usually managed with IV narcotic PCA and
      then transitioned to a combination of long-acting and short-acting oral analgesics. Because
      of the requirement for continuous carrier fluid infusion, cumbersome pump technology
      restricting mobility and supervision by a dedicated pain team to control programming of the
      pump, the PCA modality is often discontinued prior to all the patients' pain needs being met.

      The investigators' most recent study evaluated the addition of pregabalin to the pain regimen
      after spinal fusions. The study found that after the removal of the PCA modality, these
      patients had considerable pain during physical therapy (PT), and their pain was not improved
      with the addition of pregabalin.

      The IONSYS system might alleviate some of the problems encountered with conventional PCA
      systems (3,4). The system is an iontophoretic transdermal (needleless) system preprogrammed
      to deliver upon activation 40 mcg fentanyl over a 10-minute period, with up to 6 doses per
      hour. The system performs for 24 hours. The drug is embedded in a matrix gel and is only
      delivered when a current is propagated between the two poles of the system. Other than the
      usual narcotic side effects, the only specific side effect is a local dermatological reaction
      to the patch (5% had a rash, which cleared after removal). The system was designed with
      fentanyl, since hydromorphone cannot be incorporated in this type of matrix. Unlike
      hydromorphone, fentanyl is quick acting and doesn't hang around. The in-house chronic pain
      service currently puts many of their patients on IV fentanyl, because of the belief that it
      works when they have pain but is quickly metabolized.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Feasibility of IONSYS system
time frame: Day 2 following surgery for each patient
description: 1. Nursing assessment regarding the ease of setup and initiation of the IONSYS system (With regard to setup and initiation of the IONSYS, on a scale of 0-10, where 0=worst and 10=best, how would the nurse rate the system?). This will be given to the nurse who sets up the device on DOS, and nurse who sets up the device on POD 1, and the day nurse on POD 2. An average score of 7 will be considered feasible.
measure: NRS Pain Scores
time frame: Day 1 following surgery for each patient
description: 1. NRS pain (0-10 scale) on first day after surgery (POD 1) during the afternoon session of PT. In a previous study on similar patients with IV PCA, we recorded mean pain scores of 4.6 during PT. Adequate pain control is delineated as NRS ≤ 3
measure: Day of eligibility for discharge,
time frame: Up to 1 week after surgery
description: 1. Day of eligibility for discharge, as assessed by a physical therapist's observation of a patient's ability to walk at least 20 feet and climb 4 stairs. Will be delineated as either AM or PM on a day following surgery, since PT is conducted twice daily.
measure: A Oswestry Back Pain Disability Index questionnaire
time frame: 6 weeks after surgery at the Post-Op Office Visit
description: An Oswestry Back Pain Disability Index questionnaire will be conducted at the first postoperative office visit to assess whether improved pain control in the hospital had an effect on the post-discharge recovery of the patient.
measure: Level of Sedation
time frame: POD1
description: Level of sedation, as assessed by PT starting on POD1 at the initiation of PT using the University of Michigan sedation scale: (1) awake and alert; (2) minimally sedated; (3) moderately sedated; (4) deeply sedated; (5) unarousable
measure: Presence of Nausea of Vomiting
time frame: POD1 and POD2 after surgery
description: Assess whether the patient has post-operative nausea and vomiting (PONV)
measure: Satisfaction Survey
time frame: Up to 1 week
description: A satisfaction survey will be conducted prior to discharge from the hospital. It will include the following questions: (1) Was the patient's pain adequately treated? (Y/N); (2) What was the patient's worst pain level after surgery? (0-10 scale); (3) Was the IONSYS device explained? (Y/N); (4) Did the patient have side effects to the IONSYS? (Y/N); (5) Was the patient able to perform PT? (Y/N); (6) Overall satisfaction with IONSYS device (0-10 scale; 0=not satisfied; 10=most satisfied).
arm group label: IONSYS Administration
arm group type: Experimental
description: Patients who have elective multi-level spinal fusions under general anesthesia (who do not receive methadone) will be enrolled. In addition, all patients will receive Pepcid 20 mg, dexamethasone 10 mg, and ondansetron 4 mg.
When patients will arrive in the post anesthesia care unit (PACU), pain will initially be controlled with IV hydromorphone to achieve an NRS score of 3 or less. Once transferred to the step down unit (SDU), the IONSYS patch will be applied. IONSYS should be utilized when they have pain, but rescue analgesia will be available. If severe pain continues, the chronic pain service will be consulted, to potentially change the medications.
Patients will be assessed for pain at rest and with PT in the AM and PM of POD 1 and POD 2. The IONSYS system will be discontinued after 48 hours, and a total dose of fentanyl received per 24 hours will be recorded. PT milestones for discharge will be assessed on the afternoon of POD 1 and POD 2.
intervention type: Device
intervention name: IONSYS Patch
description: Patient controlled transdermal fentanyl patch, IONSYS, applied to patient in place of a PCA.
arm group label: IONSYS Administration
other name: Patient Controlled Transdermal Fentanyl Patch
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Michael Urban, M.D.
role: Principal Investigator
affiliation: Hospital for Special Surgery, New York
citation: Fletcher D, Martinez V. Opioid-induced hyperalgesia in patients after surgery: a systematic review and a meta-analysis. Br J Anaesth. 2014 Jun;112(6):991-1004. doi: 10.1093/bja/aeu137.
PMID: 24829420
citation: White PF. The changing role of non-opioid analgesic techniques in the management of postoperative pain. Anesth Analg. 2005 Nov;101(5 Suppl):S5-S22. doi: 10.1213/01.ANE.0000177099.28914.A7.
PMID: 16334489
citation: Scott LJ. Fentanyl Iontophoretic Transdermal System: A Review in Acute Postoperative Pain. Clin Drug Investig. 2016 Apr;36(4):321-30. doi: 10.1007/s40261-016-0387-x.
PMID: 26968174
citation: Mayes S, Ferrone M. Fentanyl HCl patient-controlled iontophoretic transdermal system for the management of acute postoperative pain. Ann Pharmacother. 2006 Dec;40(12):2178-86. doi: 10.1345/aph.1H135.
PMID: 17164395
responsible party type: Sponsor
mesh term: Spinal Injuries
mesh term: Fentanyl
sharing ipd: No