<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/NCT03023696</url>
  </required_header>
  <id_info>
    <org_study_id>16-353</org_study_id>
    <nct_id>NCT03023696</nct_id>
  </id_info>
  <brief_title>Can Prophylactic Foraminotomy Prevent C5 Palsy</brief_title>
  <official_title>A Randomized, Prospective Study Determining the Impact of Prophylactic Bilateral Foraminotomy During Cervical Decompression on C5 Palsy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Cleveland Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Southern California</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The Cleveland Clinic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      C5 palsy (C5P) is a well-known, although rare complication of cervical spine decompression&#xD;
      surgery. In severe forms, C5P causes debilitating upper extremity weakness involving the&#xD;
      deltoids and/or biceps brachii muscles, ultimately diminishing these patients' quality of&#xD;
      life. Furthermore, about half of patients with C5P present with sensory deficits and/or&#xD;
      intractable pain in addition to the muscle weakness.&#xD;
&#xD;
      Prophylactic bilateral foraminotomy at the C5 level during cervical decompression surgery has&#xD;
      been studied recently with the hope that it will minimize the risk of developing a C5 nerve&#xD;
      root palsy postoperatively. Although the current literature provides some support for this&#xD;
      claim, there are insufficient data establishing this technique as a proven measure to reduce&#xD;
      the incidence of C5P. In the present study, we seek to evaluate the effect of bilateral&#xD;
      foraminotomy on postoperative C5P incidence rates.&#xD;
&#xD;
      Bilateral foraminotomy has been correlated with a reduced risk of developing C5P following&#xD;
      cervical decompression surgery, but an identical foraminotomy procedure has never been&#xD;
      applied in a randomized manner to all qualifying patients in a study. Additionally,&#xD;
      prophylactic foraminotomy has only been prospectively studied during laminoplasty. In the&#xD;
      proposed study, bilateral foraminotomy will be randomized to patients receiving cervical&#xD;
      decompression surgery (laminoplasty, laminectomy, fusion). This is a multicenter randomized&#xD;
      trial, including the following sites: Cleveland Clinic, Columbia University Medical Center,&#xD;
      and University of Southern California Spine Center. Patients undergoing cervical&#xD;
      decompression surgery will be consented and enrolled if they meet the inclusion and exclusion&#xD;
      criteria. Subsequently, incidence of C5P will be monitored to determine efficacy of&#xD;
      prophylactic C5 bilateral foraminotomy during cervical decompression.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Introduction:&#xD;
&#xD;
      C5 palsy (C5P) is a well-known, although rare complication of cervical spine decompression&#xD;
      surgery.1,2 In severe forms, C5P causes debilitating upper extremity weakness involving the&#xD;
      deltoids and/or biceps brachii muscles, ultimately diminishing these patients' quality of&#xD;
      life.3 Furthermore, about half of patients with C5P present with sensory deficits and/or&#xD;
      intractable pain in addition to the muscle weakness.5 Fortunately, almost all cases of C5P&#xD;
      present unilaterally. The deficit is typically quantified and diagnosed using each patient's&#xD;
      manual muscle test (MMT) score (rating 0-5). The American Medical Association impairment&#xD;
      rating guide grades the MMT as follows: Grade 0 = no perceptible muscle contraction; Grade 1&#xD;
      = muscle contraction palpable, but no motion; Grade 2 = motion of the part only with gravity&#xD;
      reduced; Grade 3 = muscle can hold the part in the test position against gravity alone; Grade&#xD;
      4 = patient can move the part through the full range of active motion against &quot;some&quot;&#xD;
      resistance; Grade 5 = patient can move the part through the full active range of motion&#xD;
      against &quot;full&quot; resistance. C5P is defined as: a reduction of at least 1 in deltoid and/or&#xD;
      biceps brachii scores compared to preoperative scores, without any deterioration of&#xD;
      myelopathic symptoms.5&#xD;
&#xD;
      Although a uniform understanding of the etiology and mechanism of C5P is not yet established,&#xD;
      certain hypotheses have gained recognition. One prominent hypothesis, called the tethering&#xD;
      phenomenon, suggests that following decompression, posterior shift of the cord produces&#xD;
      traction on the nerve root resulting in a nerve root lesion. Other, less agreed upon&#xD;
      hypotheses include: inadvertent injury to the nerve root during surgery, spinal cord&#xD;
      ischemia, segmental spinal cord disorder, and reperfusion injury of the spinal cord. As the&#xD;
      pathogenesis of C5P is uncovered, concerted efforts to minimize the incidence of this&#xD;
      unfortunate complication have been undertaken.5&#xD;
&#xD;
      Prophylactic bilateral foraminotomy at the C5 level during cervical decompression surgery has&#xD;
      been studied recently with the hope that it will minimize the risk of developing a C5 nerve&#xD;
      root palsy postoperatively.6,7,8 Although the current literature provides some support for&#xD;
      this claim, there are insufficient data establishing this technique as a proven measure to&#xD;
      reduce the incidence of C5P. In the present study, we seek to evaluate the effect of&#xD;
      bilateral foraminotomy on postoperative C5P incidence rates.&#xD;
&#xD;
      Background:&#xD;
&#xD;
      Komagata et al.7 performed a retrospective study to investigate preoperative risk factors&#xD;
      that may cause postoperative C5P. The study included 305 cases of cervical expansive&#xD;
      laminoplasty performed for spondylotic myelopathy or ossification of the posterior&#xD;
      longitudinal ligament. No specific risk factors were found to be associated with higher&#xD;
      incidence of C5P. However, bilateral partial foraminotomy was found to be effective in&#xD;
      preventing C5P, with C5P occurring in 1 gutter (0.6%) in the foraminotomy group and in 12&#xD;
      gutters (4.0%) in the non-foraminotomy group (p&lt;0.05).&#xD;
&#xD;
      Interestingly, preoperative anatomical measurements have been suggested to correlate with&#xD;
      risk of developing C5P. Lubelski et al.9 performed a retrospective study to determine whether&#xD;
      postoperative C5P can be predicted from preoperative antero-posterior diameter (APD),&#xD;
      foraminal diameter (FD), and/or cord-lamina angle (CLA). 98 consecutive patients who&#xD;
      underwent either anterior or posterior decompression surgery at C4-C5 for spondylotic&#xD;
      myelopathy were analyzed. It was found that for every 1-mm increase in APD and FD, the odds&#xD;
      of developing palsy decrease 69% (p&lt;0.01) and decrease 98% (p&lt;0.01), respectively. In&#xD;
      contrast, for every 1-degree increase in CLA, the odds of developing palsy increase by 43%&#xD;
      (p&lt;0.01). Furthermore, Lubelski et al. used these three preoperative parameters - APD, FD,&#xD;
      and CLA - to create a nomogram that predicts the probability that a patient will develop C5&#xD;
      palsy. This nomogram will be investigated for validity in the current study.&#xD;
&#xD;
      Preliminary Studies:&#xD;
&#xD;
      In addition to the study mentioned above, several authors have demonstrated the efficacy of&#xD;
      prophylactic C5 foraminotomy during laminoplasty to prevent postoperative C5P. Sasai et al.7&#xD;
      performed the first prospective study using microcervical foraminotomy (MCF) during cervical&#xD;
      laminoplasty as a prophylactic measure to prevent C5P. MCF was used selectively in patients&#xD;
      with EMG abnormalities (Group A), and decreased the incidence of postoperative C5P compared&#xD;
      to a group that did not have EMG studies or MCF performed (Group B). No patients in Group A&#xD;
      and three patients in Group B experienced postoperative C5P (0% vs. 8.1%; p=0.035). No&#xD;
      adverse outcomes were reported in this study. Based on these results, the authors suggested&#xD;
      preexisting subclinical C5 root compression as a cause of C5P after posterior cervical&#xD;
      decompression for myelopathy.&#xD;
&#xD;
      In 2012, Katsumi et al.5 performed a prospective, non-randomized study analyzing whether&#xD;
      bilateral C5 foraminotomy can prevent C5P after open-door laminoplasty. Prophylactic&#xD;
      bilateral foraminotomy done on 141 consecutive patients was seen to significantly decrease&#xD;
      the incidence of postoperative C5P compared to a control group (1.4% and 6.4%, respectively;&#xD;
      p&lt;0.05). These results support the hypothesis that preoperative C5 foraminal stenosis is&#xD;
      associated with a higher risk of C5P. Furthermore, these findings are consistent with the&#xD;
      tethering phenomenon hypothesis regarding the pathomechanism of C5P. The only two patients in&#xD;
      this study who developed C5P after undergoing prophylactic foraminotomy did not receive&#xD;
      meticulous decompression of the C5 nerve root, leaving residual superior articular process.&#xD;
      No patients in either group experienced postoperative infection or durotomy. Although the&#xD;
      average operative time was longer in the foraminotomy group (102 minutes and 129 minutes,&#xD;
      p&lt;0.01), there was no significant difference in intraoperative blood loss between the two&#xD;
      groups. In order to better elucidate the true effect of bilateral C5 foraminotomy, the&#xD;
      procedure must be performed uniformly and randomized to all patients included.&#xD;
&#xD;
      With the current literature providing some evidence to suggest the efficacy of prophylactic&#xD;
      bilateral C5 foraminotomies to reduce the incidence of postoperative C5P, there remains a&#xD;
      need for a randomized, prospective study to investigate foraminotomy as a potentially&#xD;
      beneficial procedure to all patients undergoing cervical decompression.&#xD;
&#xD;
      Significance of Proposed Study Bilateral foraminotomy has been correlated with a reduced risk&#xD;
      of developing C5P following cervical decompression surgery, but an identical foraminotomy&#xD;
      procedure has never been applied in a randomized manner to all qualifying patients in a&#xD;
      study.5,6,7 Additionally, prophylactic foraminotomy has only been prospectively studied&#xD;
      during laminoplasty. In the proposed study, bilateral foraminotomy will be randomized to&#xD;
      patients receiving cervical decompression surgery (laminoplasty, laminectomy, fusion).&#xD;
      Subsequently, incidence of C5P as well as other surgical complications will be monitored to&#xD;
      determine efficacy of prophylactic C5 bilateral foraminotomy during cervical decompression.&#xD;
&#xD;
      Research Procedures:&#xD;
&#xD;
      This is a multicenter randomized trial, including the following sites: Cleveland Clinic,&#xD;
      Columbia University Medical Center, and University of Southern California Spine Center.&#xD;
      Patients undergoing cervical decompression surgery will be consented and enrolled if they&#xD;
      meet the inclusion and exclusion criteria detailed above. The EPIC Electronic Medical Record&#xD;
      database will be queried to retrieve medical records consistent with the study sample and to&#xD;
      determine all cervical decompression surgeries. Patients' sex, race, date of birth, BMI,&#xD;
      medical comorbidities, medications, history of spinal trauma or surgical intervention,&#xD;
      smoking status/ history, spinal levels involved, type of surgery, operating surgeon, length&#xD;
      of hospital stay, operative time, blood loss, in-hospital complications noted and patient&#xD;
      complications following surgery will be obtained. Additionally, preoperative anteroposterior&#xD;
      diameter of the spinal canal at C4-C5, ipsilateral foraminal diameter at C4-C5, and the&#xD;
      morphological relationship between the spinal cord and the ipsilateral lamina (cord-lamina&#xD;
      angle) will be obtained. Clinical outcome measures will be analyzed using standard&#xD;
      statistical methods.&#xD;
&#xD;
      Intervention:&#xD;
&#xD;
      In addition to the decompression technique indicated directly for treatment of cervical&#xD;
      myelopathy, bilateral keyhole foraminotomies will be done prophylactically in an attempt to&#xD;
      minimize postoperative complications, specifically C5 Palsy. Under microscopic or loop&#xD;
      magnification, a high-speed burr is used to perform the foraminotomy. The keyhole&#xD;
      foraminotomy begins at the lamina-facet junction, with careful consideration of the amount of&#xD;
      facet resection. Typically, only the medial one third is drilled. Then a 1- or 2-mm Kerrison&#xD;
      punch can be carefully placed over the nerve root and then used to undercut the facet,&#xD;
      ensuring that the spine is not destabilized by the foraminotomy. The amount of facet&#xD;
      resection must not exceed 50% in order to preserve spine stability.&#xD;
&#xD;
      Consent:&#xD;
&#xD;
      All patients will be enrolled after completion of the attached informed consent form. All&#xD;
      patients' information in this prospective study will be treated as confidential. This study&#xD;
      involves no risk to the physician, or OR staff. A cervical foraminotomy is a common, short&#xD;
      procedure (e.g. 5 minutes) that involves making more room for a cervical nerve root as it&#xD;
      exits the spinal column. It is a procedure that all surgeons perform routinely, and in no way&#xD;
      put the patient at risk for spine structural problems. Similarly, it does not impart&#xD;
      additional measurable risk to the patient of neurological injury or infection over that risk&#xD;
      already being incurred by the patient for the index procedure. Patients who are under the age&#xD;
      of 18 will be excluded for previously mentioned scientific reasons. Women and minorities are&#xD;
      expected to participate proportionally to their numbers diagnosed with cervical myelopathy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 2016</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</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>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>C5 Palsy</measure>
    <time_frame>Upon discharge, 2 weeks postoperatively and 3 months postoperatively</time_frame>
    <description>Using manual muscle testing and upper extremity sensory exam findings to determine C5 palsy status. C5P is defined as: a reduction of at least 1 in deltoid and/or biceps brachii manual muscle testing scores compared to preoperative scores, without any deterioration of myelopathic symptoms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Preoperative anatomic measurements</measure>
    <time_frame>Preoperative</time_frame>
    <description>Anteroposterior diameter, foraminal diameter and cord-lamina angle will be determined using preoperative computed tomography scan</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Operative time</measure>
    <time_frame>Intra-operative measurement</time_frame>
    <description>Time length of operation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood loss</measure>
    <time_frame>Intra-operative measurement</time_frame>
    <description>Amount of blood loss during surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Back Pain</measure>
    <time_frame>Preoperative, 2 weeks postoperative and 3 months postoperative</time_frame>
    <description>Visual Analog Scale for Back Pain (0-10)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Leg Pain</measure>
    <time_frame>Preoperative, 2 weeks postoperative and 3 months postoperative</time_frame>
    <description>Visual Analog Scale for Leg Pain (0-10)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Emergency department visit</measure>
    <time_frame>within 90 days postoperatively</time_frame>
    <description>Subject has Emergency department visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Readmission to hospital</measure>
    <time_frame>within 90 days postoperatively</time_frame>
    <description>Subject is readmitted to hospital within 90 days post-operatively</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">480</enrollment>
  <condition>Myelopathy, Compressive</condition>
  <condition>Radiculopathy, Cervical</condition>
  <condition>C5 Palsy</condition>
  <arm_group>
    <arm_group_label>Foraminotomy Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Prophylactic bilateral cervical keyhole foraminotomy will be done in addition to their decompression surgery</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cervical decompression will be done without prophylactic bilateral foraminotomy</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Bilateral Cervical Keyhole Foraminotomy</intervention_name>
    <description>Under microscopic or loop magnification, a high-speed burr is used to perform the foraminotomy. The keyhole foraminotomy begins at the lamina-facet junction, with careful consideration of the amount of facet resection. Typically, only the medial one third is drilled. Then a 1- or 2-mm Kerrison punch can be carefully placed over the nerve root and then used to undercut the facet, ensuring that the spine is not destabilized by the foraminotomy. The amount of facet resection must not exceed 50% in order to preserve spine stability.</description>
    <arm_group_label>Foraminotomy Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Cervical Decompression</intervention_name>
    <description>Cervical decompression for myelopathy, including the following procedures: laminoplasty, laminectomy, discectomy and fusion</description>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_label>Foraminotomy Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Cleveland Clinic patients who have been diagnosed with cervical myelopathy, without&#xD;
             radiculopathy, and will undergo posterior cervical decompression involving the C4-C5&#xD;
             interspace between 2016 and 2018. This includes patients undergoing cervical&#xD;
             laminoplasty and cervical laminectomy and fusion.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any patient younger than 18 years of age will not be included on the basis of skeletal&#xD;
             immaturity. Patients with C5 radiculopathy - defined in our study as the existence of&#xD;
             preoperative deltoid muscle weakness in grade 3 or less by MMT - will be excluded. Any&#xD;
             patients who have undergone previous cervical spine surgery, or who have any spinal&#xD;
             malignancy, trauma or infection will be excluded in order to eliminate the confounding&#xD;
             effect of multiple surgical interventions.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thomas E Mroz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Cleveland Clinic</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>David Chelnick, BS</last_name>
    <phone>2164451741</phone>
    <email>chelnid2@ccf.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>Cleveland Clinic Foundation</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>David Chelnick, BS</last_name>
      <phone>216-445-1741</phone>
      <email>chelnid2@ccf.org</email>
    </contact>
    <contact_backup>
      <last_name>Emily Fisher, MPH</last_name>
      <email>fishere3@ccf.org</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Wada E, Suzuki S, Kanazawa A, Matsuoka T, Miyamoto S, Yonenobu K. Subtotal corpectomy versus laminoplasty for multilevel cervical spondylotic myelopathy: a long-term follow-up study over 10 years. Spine (Phila Pa 1976). 2001 Jul 1;26(13):1443-7; discussion 1448. doi: 10.1097/00007632-200107010-00011.</citation>
    <PMID>11458148</PMID>
  </reference>
  <reference>
    <citation>Epstein NE, Hollingsworth R. C5 Nerve root palsies following cervical spine surgery: A review. Surg Neurol Int. 2015 May 7;6(Suppl 4):S154-63. doi: 10.4103/2152-7806.156556. eCollection 2015.</citation>
    <PMID>26005577</PMID>
  </reference>
  <reference>
    <citation>Miller JA, Lubelski D, Alvin MD, Benzel EC, Mroz TE. C5 palsy after posterior cervical decompression and fusion: cost and quality-of-life implications. Spine J. 2014 Dec 1;14(12):2854-60. doi: 10.1016/j.spinee.2014.03.038. Epub 2014 Apr 3.</citation>
    <PMID>24704502</PMID>
  </reference>
  <reference>
    <citation>Sakaura H, Hosono N, Mukai Y, Ishii T, Yoshikawa H. C5 palsy after decompression surgery for cervical myelopathy: review of the literature. Spine (Phila Pa 1976). 2003 Nov 1;28(21):2447-51. doi: 10.1097/01.BRS.0000090833.96168.3F.</citation>
    <PMID>14595162</PMID>
  </reference>
  <reference>
    <citation>Katsumi K, Yamazaki A, Watanabe K, Ohashi M, Shoji H. Can prophylactic bilateral C4/C5 foraminotomy prevent postoperative C5 palsy after open-door laminoplasty?: a prospective study. Spine (Phila Pa 1976). 2012 Apr 20;37(9):748-54. doi: 10.1097/BRS.0b013e3182326957.</citation>
    <PMID>21912316</PMID>
  </reference>
  <reference>
    <citation>Komagata M, Nishiyama M, Endo K, Ikegami H, Tanaka S, Imakiire A. Prophylaxis of C5 palsy after cervical expansive laminoplasty by bilateral partial foraminotomy. Spine J. 2004 Nov-Dec;4(6):650-5. doi: 10.1016/j.spinee.2004.03.022.</citation>
    <PMID>15541697</PMID>
  </reference>
  <reference>
    <citation>Sasai K, Saito T, Akagi S, Kato I, Ohnari H, Iida H. Preventing C5 palsy after laminoplasty. Spine (Phila Pa 1976). 2003 Sep 1;28(17):1972-7. doi: 10.1097/01.BRS.0000083237.94535.46.</citation>
    <PMID>12973145</PMID>
  </reference>
  <reference>
    <citation>Lubelski D, Derakhshan A, Nowacki AS, Wang JC, Steinmetz MP, Benzel EC, Mroz TE. Predicting C5 palsy via the use of preoperative anatomic measurements. Spine J. 2014 Sep 1;14(9):1895-901. doi: 10.1016/j.spinee.2013.10.038. Epub 2013 Nov 10.</citation>
    <PMID>24225009</PMID>
  </reference>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>January 13, 2017</study_first_submitted>
  <study_first_submitted_qc>January 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 18, 2017</study_first_posted>
  <last_update_submitted>January 4, 2023</last_update_submitted>
  <last_update_submitted_qc>January 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 5, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Cleveland Clinic</investigator_affiliation>
    <investigator_full_name>Thomas Mroz, MD</investigator_full_name>
    <investigator_title>Director, Center for Spine Health</investigator_title>
  </responsible_party>
  <keyword>C5 Palsy</keyword>
  <keyword>foraminotomy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paralysis</mesh_term>
    <mesh_term>Radiculopathy</mesh_term>
    <mesh_term>Spinal Cord Diseases</mesh_term>
    <mesh_term>Spinal Cord Compression</mesh_term>
  </condition_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/NCT03023696
org study id: 16-353
nct id: NCT03023696
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
C5 palsy (C5P) is a well-known, although rare complication of cervical spine decompression
      surgery. In severe forms, C5P causes debilitating upper extremity weakness involving the
      deltoids and/or biceps brachii muscles, ultimately diminishing these patients' quality of
      life. Furthermore, about half of patients with C5P present with sensory deficits and/or
      intractable pain in addition to the muscle weakness.

      Prophylactic bilateral foraminotomy at the C5 level during cervical decompression surgery has
      been studied recently with the hope that it will minimize the risk of developing a C5 nerve
      root palsy postoperatively. Although the current literature provides some support for this
      claim, there are insufficient data establishing this technique as a proven measure to reduce
      the incidence of C5P. In the present study, we seek to evaluate the effect of bilateral
      foraminotomy on postoperative C5P incidence rates.

      Bilateral foraminotomy has been correlated with a reduced risk of developing C5P following
      cervical decompression surgery, but an identical foraminotomy procedure has never been
      applied in a randomized manner to all qualifying patients in a study. Additionally,
      prophylactic foraminotomy has only been prospectively studied during laminoplasty. In the
      proposed study, bilateral foraminotomy will be randomized to patients receiving cervical
      decompression surgery (laminoplasty, laminectomy, fusion). This is a multicenter randomized
      trial, including the following sites: Cleveland Clinic, Columbia University Medical Center,
      and University of Southern California Spine Center. Patients undergoing cervical
      decompression surgery will be consented and enrolled if they meet the inclusion and exclusion
      criteria. Subsequently, incidence of C5P will be monitored to determine efficacy of
      prophylactic C5 bilateral foraminotomy during cervical decompression.
Introduction:

      C5 palsy (C5P) is a well-known, although rare complication of cervical spine decompression
      surgery.1,2 In severe forms, C5P causes debilitating upper extremity weakness involving the
      deltoids and/or biceps brachii muscles, ultimately diminishing these patients' quality of
      life.3 Furthermore, about half of patients with C5P present with sensory deficits and/or
      intractable pain in addition to the muscle weakness.5 Fortunately, almost all cases of C5P
      present unilaterally. The deficit is typically quantified and diagnosed using each patient's
      manual muscle test (MMT) score (rating 0-5). The American Medical Association impairment
      rating guide grades the MMT as follows: Grade 0 = no perceptible muscle contraction; Grade 1
      = muscle contraction palpable, but no motion; Grade 2 = motion of the part only with gravity
      reduced; Grade 3 = muscle can hold the part in the test position against gravity alone; Grade
      4 = patient can move the part through the full range of active motion against "some"
      resistance; Grade 5 = patient can move the part through the full active range of motion
      against "full" resistance. C5P is defined as: a reduction of at least 1 in deltoid and/or
      biceps brachii scores compared to preoperative scores, without any deterioration of
      myelopathic symptoms.5

      Although a uniform understanding of the etiology and mechanism of C5P is not yet established,
      certain hypotheses have gained recognition. One prominent hypothesis, called the tethering
      phenomenon, suggests that following decompression, posterior shift of the cord produces
      traction on the nerve root resulting in a nerve root lesion. Other, less agreed upon
      hypotheses include: inadvertent injury to the nerve root during surgery, spinal cord
      ischemia, segmental spinal cord disorder, and reperfusion injury of the spinal cord. As the
      pathogenesis of C5P is uncovered, concerted efforts to minimize the incidence of this
      unfortunate complication have been undertaken.5

      Prophylactic bilateral foraminotomy at the C5 level during cervical decompression surgery has
      been studied recently with the hope that it will minimize the risk of developing a C5 nerve
      root palsy postoperatively.6,7,8 Although the current literature provides some support for
      this claim, there are insufficient data establishing this technique as a proven measure to
      reduce the incidence of C5P. In the present study, we seek to evaluate the effect of
      bilateral foraminotomy on postoperative C5P incidence rates.

      Background:

      Komagata et al.7 performed a retrospective study to investigate preoperative risk factors
      that may cause postoperative C5P. The study included 305 cases of cervical expansive
      laminoplasty performed for spondylotic myelopathy or ossification of the posterior
      longitudinal ligament. No specific risk factors were found to be associated with higher
      incidence of C5P. However, bilateral partial foraminotomy was found to be effective in
      preventing C5P, with C5P occurring in 1 gutter (0.6%) in the foraminotomy group and in 12
      gutters (4.0%) in the non-foraminotomy group (p<0.05).

      Interestingly, preoperative anatomical measurements have been suggested to correlate with
      risk of developing C5P. Lubelski et al.9 performed a retrospective study to determine whether
      postoperative C5P can be predicted from preoperative antero-posterior diameter (APD),
      foraminal diameter (FD), and/or cord-lamina angle (CLA). 98 consecutive patients who
      underwent either anterior or posterior decompression surgery at C4-C5 for spondylotic
      myelopathy were analyzed. It was found that for every 1-mm increase in APD and FD, the odds
      of developing palsy decrease 69% (p<0.01) and decrease 98% (p<0.01), respectively. In
      contrast, for every 1-degree increase in CLA, the odds of developing palsy increase by 43%
      (p<0.01). Furthermore, Lubelski et al. used these three preoperative parameters - APD, FD,
      and CLA - to create a nomogram that predicts the probability that a patient will develop C5
      palsy. This nomogram will be investigated for validity in the current study.

      Preliminary Studies:

      In addition to the study mentioned above, several authors have demonstrated the efficacy of
      prophylactic C5 foraminotomy during laminoplasty to prevent postoperative C5P. Sasai et al.7
      performed the first prospective study using microcervical foraminotomy (MCF) during cervical
      laminoplasty as a prophylactic measure to prevent C5P. MCF was used selectively in patients
      with EMG abnormalities (Group A), and decreased the incidence of postoperative C5P compared
      to a group that did not have EMG studies or MCF performed (Group B). No patients in Group A
      and three patients in Group B experienced postoperative C5P (0% vs. 8.1%; p=0.035). No
      adverse outcomes were reported in this study. Based on these results, the authors suggested
      preexisting subclinical C5 root compression as a cause of C5P after posterior cervical
      decompression for myelopathy.

      In 2012, Katsumi et al.5 performed a prospective, non-randomized study analyzing whether
      bilateral C5 foraminotomy can prevent C5P after open-door laminoplasty. Prophylactic
      bilateral foraminotomy done on 141 consecutive patients was seen to significantly decrease
      the incidence of postoperative C5P compared to a control group (1.4% and 6.4%, respectively;
      p<0.05). These results support the hypothesis that preoperative C5 foraminal stenosis is
      associated with a higher risk of C5P. Furthermore, these findings are consistent with the
      tethering phenomenon hypothesis regarding the pathomechanism of C5P. The only two patients in
      this study who developed C5P after undergoing prophylactic foraminotomy did not receive
      meticulous decompression of the C5 nerve root, leaving residual superior articular process.
      No patients in either group experienced postoperative infection or durotomy. Although the
      average operative time was longer in the foraminotomy group (102 minutes and 129 minutes,
      p<0.01), there was no significant difference in intraoperative blood loss between the two
      groups. In order to better elucidate the true effect of bilateral C5 foraminotomy, the
      procedure must be performed uniformly and randomized to all patients included.

      With the current literature providing some evidence to suggest the efficacy of prophylactic
      bilateral C5 foraminotomies to reduce the incidence of postoperative C5P, there remains a
      need for a randomized, prospective study to investigate foraminotomy as a potentially
      beneficial procedure to all patients undergoing cervical decompression.

      Significance of Proposed Study Bilateral foraminotomy has been correlated with a reduced risk
      of developing C5P following cervical decompression surgery, but an identical foraminotomy
      procedure has never been applied in a randomized manner to all qualifying patients in a
      study.5,6,7 Additionally, prophylactic foraminotomy has only been prospectively studied
      during laminoplasty. In the proposed study, bilateral foraminotomy will be randomized to
      patients receiving cervical decompression surgery (laminoplasty, laminectomy, fusion).
      Subsequently, incidence of C5P as well as other surgical complications will be monitored to
      determine efficacy of prophylactic C5 bilateral foraminotomy during cervical decompression.

      Research Procedures:

      This is a multicenter randomized trial, including the following sites: Cleveland Clinic,
      Columbia University Medical Center, and University of Southern California Spine Center.
      Patients undergoing cervical decompression surgery will be consented and enrolled if they
      meet the inclusion and exclusion criteria detailed above. The EPIC Electronic Medical Record
      database will be queried to retrieve medical records consistent with the study sample and to
      determine all cervical decompression surgeries. Patients' sex, race, date of birth, BMI,
      medical comorbidities, medications, history of spinal trauma or surgical intervention,
      smoking status/ history, spinal levels involved, type of surgery, operating surgeon, length
      of hospital stay, operative time, blood loss, in-hospital complications noted and patient
      complications following surgery will be obtained. Additionally, preoperative anteroposterior
      diameter of the spinal canal at C4-C5, ipsilateral foraminal diameter at C4-C5, and the
      morphological relationship between the spinal cord and the ipsilateral lamina (cord-lamina
      angle) will be obtained. Clinical outcome measures will be analyzed using standard
      statistical methods.

      Intervention:

      In addition to the decompression technique indicated directly for treatment of cervical
      myelopathy, bilateral keyhole foraminotomies will be done prophylactically in an attempt to
      minimize postoperative complications, specifically C5 Palsy. Under microscopic or loop
      magnification, a high-speed burr is used to perform the foraminotomy. The keyhole
      foraminotomy begins at the lamina-facet junction, with careful consideration of the amount of
      facet resection. Typically, only the medial one third is drilled. Then a 1- or 2-mm Kerrison
      punch can be carefully placed over the nerve root and then used to undercut the facet,
      ensuring that the spine is not destabilized by the foraminotomy. The amount of facet
      resection must not exceed 50% in order to preserve spine stability.

      Consent:

      All patients will be enrolled after completion of the attached informed consent form. All
      patients' information in this prospective study will be treated as confidential. This study
      involves no risk to the physician, or OR staff. A cervical foraminotomy is a common, short
      procedure (e.g. 5 minutes) that involves making more room for a cervical nerve root as it
      exits the spinal column. It is a procedure that all surgeons perform routinely, and in no way
      put the patient at risk for spine structural problems. Similarly, it does not impart
      additional measurable risk to the patient of neurological injury or infection over that risk
      already being incurred by the patient for the index procedure. Patients who are under the age
      of 18 will be excluded for previously mentioned scientific reasons. Women and minorities are
      expected to participate proportionally to their numbers diagnosed with cervical myelopathy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: C5 Palsy
time frame: Upon discharge, 2 weeks postoperatively and 3 months postoperatively
description: Using manual muscle testing and upper extremity sensory exam findings to determine C5 palsy status. C5P is defined as: a reduction of at least 1 in deltoid and/or biceps brachii manual muscle testing scores compared to preoperative scores, without any deterioration of myelopathic symptoms.
measure: Preoperative anatomic measurements
time frame: Preoperative
description: Anteroposterior diameter, foraminal diameter and cord-lamina angle will be determined using preoperative computed tomography scan
measure: Operative time
time frame: Intra-operative measurement
description: Time length of operation
measure: Blood loss
time frame: Intra-operative measurement
description: Amount of blood loss during surgery
measure: Back Pain
time frame: Preoperative, 2 weeks postoperative and 3 months postoperative
description: Visual Analog Scale for Back Pain (0-10)
measure: Leg Pain
time frame: Preoperative, 2 weeks postoperative and 3 months postoperative
description: Visual Analog Scale for Leg Pain (0-10)
measure: Emergency department visit
time frame: within 90 days postoperatively
description: Subject has Emergency department visit
measure: Readmission to hospital
time frame: within 90 days postoperatively
description: Subject is readmitted to hospital within 90 days post-operatively
arm group label: Foraminotomy Group
arm group type: Experimental
description: Prophylactic bilateral cervical keyhole foraminotomy will be done in addition to their decompression surgery
arm group label: Control Group
arm group type: Active Comparator
description: Cervical decompression will be done without prophylactic bilateral foraminotomy
intervention type: Procedure
intervention name: Bilateral Cervical Keyhole Foraminotomy
description: Under microscopic or loop magnification, a high-speed burr is used to perform the foraminotomy. The keyhole foraminotomy begins at the lamina-facet junction, with careful consideration of the amount of facet resection. Typically, only the medial one third is drilled. Then a 1- or 2-mm Kerrison punch can be carefully placed over the nerve root and then used to undercut the facet, ensuring that the spine is not destabilized by the foraminotomy. The amount of facet resection must not exceed 50% in order to preserve spine stability.
arm group label: Foraminotomy Group
intervention type: Procedure
intervention name: Cervical Decompression
description: Cervical decompression for myelopathy, including the following procedures: laminoplasty, laminectomy, discectomy and fusion
arm group label: Control Group
arm group label: Foraminotomy Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Thomas E Mroz, MD
role: Principal Investigator
affiliation: The Cleveland Clinic
last name: David Chelnick, BS
phone: 2164451741
email: chelnid2@ccf.org
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
citation: Wada E, Suzuki S, Kanazawa A, Matsuoka T, Miyamoto S, Yonenobu K. Subtotal corpectomy versus laminoplasty for multilevel cervical spondylotic myelopathy: a long-term follow-up study over 10 years. Spine (Phila Pa 1976). 2001 Jul 1;26(13):1443-7; discussion 1448. doi: 10.1097/00007632-200107010-00011.
PMID: 11458148
citation: Epstein NE, Hollingsworth R. C5 Nerve root palsies following cervical spine surgery: A review. Surg Neurol Int. 2015 May 7;6(Suppl 4):S154-63. doi: 10.4103/2152-7806.156556. eCollection 2015.
PMID: 26005577
citation: Miller JA, Lubelski D, Alvin MD, Benzel EC, Mroz TE. C5 palsy after posterior cervical decompression and fusion: cost and quality-of-life implications. Spine J. 2014 Dec 1;14(12):2854-60. doi: 10.1016/j.spinee.2014.03.038. Epub 2014 Apr 3.
PMID: 24704502
citation: Sakaura H, Hosono N, Mukai Y, Ishii T, Yoshikawa H. C5 palsy after decompression surgery for cervical myelopathy: review of the literature. Spine (Phila Pa 1976). 2003 Nov 1;28(21):2447-51. doi: 10.1097/01.BRS.0000090833.96168.3F.
PMID: 14595162
citation: Katsumi K, Yamazaki A, Watanabe K, Ohashi M, Shoji H. Can prophylactic bilateral C4/C5 foraminotomy prevent postoperative C5 palsy after open-door laminoplasty?: a prospective study. Spine (Phila Pa 1976). 2012 Apr 20;37(9):748-54. doi: 10.1097/BRS.0b013e3182326957.
PMID: 21912316
citation: Komagata M, Nishiyama M, Endo K, Ikegami H, Tanaka S, Imakiire A. Prophylaxis of C5 palsy after cervical expansive laminoplasty by bilateral partial foraminotomy. Spine J. 2004 Nov-Dec;4(6):650-5. doi: 10.1016/j.spinee.2004.03.022.
PMID: 15541697
citation: Sasai K, Saito T, Akagi S, Kato I, Ohnari H, Iida H. Preventing C5 palsy after laminoplasty. Spine (Phila Pa 1976). 2003 Sep 1;28(17):1972-7. doi: 10.1097/01.BRS.0000083237.94535.46.
PMID: 12973145
citation: Lubelski D, Derakhshan A, Nowacki AS, Wang JC, Steinmetz MP, Benzel EC, Mroz TE. Predicting C5 palsy via the use of preoperative anatomic measurements. Spine J. 2014 Sep 1;14(9):1895-901. doi: 10.1016/j.spinee.2013.10.038. Epub 2013 Nov 10.
PMID: 24225009
responsible party type: Principal Investigator
investigator affiliation: The Cleveland Clinic
investigator full name: Thomas Mroz, MD
investigator title: Director, Center for Spine Health
mesh term: Paralysis
mesh term: Radiculopathy
mesh term: Spinal Cord Diseases
mesh term: Spinal Cord Compression
sharing ipd: No