<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/NCT03256955</url>
  </required_header>
  <id_info>
    <org_study_id>TofCuff Study</org_study_id>
    <nct_id>NCT03256955</nct_id>
  </id_info>
  <brief_title>Validation of the TOF Cuff Monitor® Which Measures Neuromuscular Block on the Upper Arm</brief_title>
  <official_title>The Comparison of the TOF Cuff Monitor® With the TOF Watch SX® Monitor:</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Christoph Czarnetzki</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Geneva</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>
      Neuromuscular blocking agents (NMBAs) are frequently used in anesthesia and quantitative&#xD;
      neuromuscular monitoring is standard care. The TOF WATCH SX® monitor is considered as one of&#xD;
      the reference monitoring devices in clinical research and clinical practice. With this&#xD;
      monitor the ulnar nerve is stimulated at the wrist and the force of the movement of the thumb&#xD;
      is measured with acceleromyography. This method requires freedom of movement of the patient's&#xD;
      thumb. Unfortunately this is not always possible due to the constraints of patient&#xD;
      positioning during the operation. The TOF Cuff® monitor is a modified non-invasive blood&#xD;
      pressure cuff that incorporates stimulating electrodes in its inner surface and is based on&#xD;
      the stimulation of the peripheral nerve in the arm (brachial plexus, ulnar and median nerves&#xD;
      principally). The evoked neuromuscular activity is recorded through the changes in pressure&#xD;
      generated in the inner part of the cuff by the muscular activity after the stimulus.&#xD;
      Moreover, this device can be used for non-invasive reading of the blood pressure. This device&#xD;
      has been validated with mechanomyography, but was never been compared with acceleromyography,&#xD;
      which is the most common used neuromuscular monitoring method.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Neuromuscular blocking agents (NMBAs) are frequently used in anesthesia for tracheal&#xD;
      intubation, artificial ventilation, and continued muscle relaxation during surgical&#xD;
      interventions. It is of particular importance to measure the neuromuscular block for several&#xD;
      reasons:&#xD;
&#xD;
        1. To monitor the onset of neuromuscular block and to intubate when deep muscular&#xD;
           relaxation is attained.&#xD;
&#xD;
        2. To choose the best antagonist and its dosage dependent of the degree of neuromuscular&#xD;
           block (for instance sugammadex for deep neuromuscular block or neostigmine for&#xD;
           superficial block).&#xD;
&#xD;
        3. To avoid antagonization of neuromuscular block in the case of complete recovery of&#xD;
           neuromuscular function.&#xD;
&#xD;
      It is proven that monitoring of neuromuscular block reduces patient mortality. It avoids&#xD;
      postoperative residual curarization, which is associated with complications such as&#xD;
      hypoxemia, bronchoaspiration and pneumonia. Therefore the development and validation of new&#xD;
      and efficacious neuromuscular monitoring devices is of great importance.&#xD;
&#xD;
      Neuromuscular monitoring is done by stimulating with an electric current a nerve and to&#xD;
      measure the response of the corresponding muscle. In clinical practice acceleromyography is&#xD;
      the most often used quantitative measurement method, because it is much easier to apply than&#xD;
      other established quantitative neuromuscular monitoring methods such as mechanomyograpy and&#xD;
      electromyography. Acceleromyography is based on the piezoelectric effect where mechanical&#xD;
      forces at play on the surfaces of certain materials, such as crystals or ceramics, induce an&#xD;
      electrical current. According to Newton's second law of motion, force equals mass times&#xD;
      acceleration (F=m x a). At constant mass, the acceleration measured and the voltage thereby&#xD;
      generated can be used to derive the force of the stimulated muscle. It is standard practice&#xD;
      to stimulate the ulnar nerve at the wrist and to measure the movement of the adductor&#xD;
      pollicis. In the research setting acceleromyography (TOF Watch SX® monitor) is an established&#xD;
      and widely used method. This method requires freedom of movement of the patient's thumb.&#xD;
      Unfortunately this is not always possible due to the constraints of patient positioning&#xD;
      during the operation. The TOF Cuff® monitor is a modified non-invasive blood pressure cuff&#xD;
      that incorporates stimulating electrodes in its inner surface and is based on the stimulation&#xD;
      of the peripheral nerve in the arm (brachial plexus, ulnar and median nerves principally).&#xD;
      The evoked neuromuscular activity is recorded through the changes in pressure generated in&#xD;
      the inner part of the cuff by the muscular activity after the stimulus. Moreover, this device&#xD;
      can be used for non-invasive reading of the blood pressure. This device has been validated&#xD;
      with mechanomyography, but was never been compared with acceleromyography, which is the most&#xD;
      common used neuromuscular monitoring method.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 23, 2017</start_date>
  <completion_date type="Actual">May 14, 2018</completion_date>
  <primary_completion_date type="Actual">May 14, 2018</primary_completion_date>
  <phase>N/A</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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Total recovery time of neuromuscular block</measure>
    <time_frame>60 to 120 minutes</time_frame>
    <description>The total recovery time, i.e. total duration of the neuromuscular block is defined as the time in minutes from start of injection of rocuronium until a normalized TOF ratio of 90% (Dur TOF 0.9). TOF = Train of Four</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Onset time</measure>
    <time_frame>1 to 4 minutes</time_frame>
    <description>time in seconds from start of injection of rocuronium until 95% depression of the first twitch (T1) of the TOF(Train of Four)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration TOF count 1</measure>
    <time_frame>20 - 30 minutes</time_frame>
    <description>Time (in minutes) from administration of rocuronium to emergence of the 1st twitch of the TOF (Dur TOFc1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration TOF 25%</measure>
    <time_frame>30 - 40 minutes</time_frame>
    <description>Time (in minutes) from administration of rocuronium to emergence of a normalized TOF ratio of 25%</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration TOF 50%</measure>
    <time_frame>30 - 50 minutes</time_frame>
    <description>Time (in minutes) from administration of rocuronium to emergence of a normalized TOF ratio of 50%</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration TOF 75%</measure>
    <time_frame>30 - 60 minutes</time_frame>
    <description>Time (in minutes) from administration of rocuronium to emergence of a normalized TOF ratio of 75%</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Neuromuscular Blockade</condition>
  <arm_group>
    <arm_group_label>Tof Watch SX and Tof Cuff</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients undergoing surgery with intubation and receiving a single intubation dose of rocuronium (0.6 mg/kg) under propofol anesthesia will have monitoring of neuromuscular block with two monitors simultaneously.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Tof cuff</intervention_name>
    <description>The Tof Cuff will be installed on one arm. After anesthesia induction the Tof Cuff will be calibrated and continuos monitoring of the neuromuscular block started until complete recovery of neuromuscular block.</description>
    <arm_group_label>Tof Watch SX and Tof Cuff</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Tof Watch SX</intervention_name>
    <description>The Tof Watch SX will be installed on the opposite arm to the Tof Cuff. After anesthesia induction the Tof Watch SX will be calibrated and continuos monitoring of the neuromuscular block started until complete recovery of neuromuscular block.</description>
    <arm_group_label>Tof Watch SX and Tof Cuff</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients, age ≥18 to 65 years&#xD;
&#xD;
          -  Patient with American Society of Anesthesiology [ASA] status I or II&#xD;
&#xD;
          -  Patient able to read and understand the information sheet and to sign and date the&#xD;
             consent form&#xD;
&#xD;
          -  Patient scheduled for elective surgery lasting at least 60 minutes&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient with a history of allergy or hypersensitivity to rocuronium&#xD;
&#xD;
          -  Patient with pacemaker&#xD;
&#xD;
          -  Patients with neuromuscular disease&#xD;
&#xD;
          -  Patients with preoperative medications known to influence neuromuscular function (for&#xD;
             instance aminoglycosides, phenytoin, lidocaine)&#xD;
&#xD;
          -  Patients with electrolyte abnormalities (for instance, hypermagnesemia)&#xD;
&#xD;
          -  Patients with a body mass index &lt;19 or &gt;30 kg m2&#xD;
&#xD;
          -  Patient having participated in any clinical trial within 30 days, inclusive, of&#xD;
             signing the informed consent form of the current trial&#xD;
&#xD;
          -  Patients undergoing interventions that need a continuous deep NMB (for surgical&#xD;
             reasons).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christoph Czarnetzki, MD</last_name>
    <role>Study Chair</role>
    <affiliation>University Hospitals of Geneva</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospitals of Geneva</name>
      <address>
        <city>Geneva</city>
        <zip>1205</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <link>
    <url>http://www.tdx.cat/handle/10803/307220</url>
    <description>Thesis for the validation of the tof cuff (in spanish)</description>
  </link>
  <reference>
    <citation>Rodiera J, Serradell A, Alvarez-Gomez JA, Aliaga L. The cuff method: a pilot study of a new method of monitoring neuromuscular function. Acta Anaesthesiol Scand. 2005 Nov;49(10):1552-8. doi: 10.1111/j.1399-6576.2005.00777.x.</citation>
    <PMID>16223405</PMID>
  </reference>
  <reference>
    <citation>Veiga Ruiz G, Garcia Cayuela J, Orozco Montes J, Parreno Caparros M, Garcia Rojo B, Aguayo Albasini JL. Monitoring intraoperative neuromuscular blockade and blood pressure with one device (TOF-Cuff): A comparative study with mechanomyography and invasive blood pressure. Rev Esp Anestesiol Reanim. 2017 Dec;64(10):560-567. doi: 10.1016/j.redar.2017.03.013. Epub 2017 Jun 27. English, Spanish.</citation>
    <PMID>28662770</PMID>
  </reference>
  <results_reference>
    <citation>Sfeir Machado E, Keli-Barcelos G, Dupuis-Lozeron E, Tramer MR, Czarnetzki C. Assessment of spontaneous neuromuscular recovery: A comparison of the TOF-Cuff(R) with the TOF Watch SX(R). Acta Anaesthesiol Scand. 2020 Feb;64(2):173-179. doi: 10.1111/aas.13487. Epub 2019 Oct 28.</citation>
    <PMID>31593293</PMID>
  </results_reference>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>August 16, 2017</study_first_submitted>
  <study_first_submitted_qc>August 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 22, 2017</study_first_posted>
  <last_update_submitted>October 29, 2019</last_update_submitted>
  <last_update_submitted_qc>October 29, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 31, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital, Geneva</investigator_affiliation>
    <investigator_full_name>Christoph Czarnetzki</investigator_full_name>
    <investigator_title>Médecin adjoint</investigator_title>
  </responsible_party>
  <keyword>Validation study for a neuromuscular monitoring device</keyword>
  <!-- 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/NCT03256955
org study id: TofCuff Study
nct id: NCT03256955
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Neuromuscular blocking agents (NMBAs) are frequently used in anesthesia and quantitative
      neuromuscular monitoring is standard care. The TOF WATCH SX® monitor is considered as one of
      the reference monitoring devices in clinical research and clinical practice. With this
      monitor the ulnar nerve is stimulated at the wrist and the force of the movement of the thumb
      is measured with acceleromyography. This method requires freedom of movement of the patient's
      thumb. Unfortunately this is not always possible due to the constraints of patient
      positioning during the operation. The TOF Cuff® monitor is a modified non-invasive blood
      pressure cuff that incorporates stimulating electrodes in its inner surface and is based on
      the stimulation of the peripheral nerve in the arm (brachial plexus, ulnar and median nerves
      principally). The evoked neuromuscular activity is recorded through the changes in pressure
      generated in the inner part of the cuff by the muscular activity after the stimulus.
      Moreover, this device can be used for non-invasive reading of the blood pressure. This device
      has been validated with mechanomyography, but was never been compared with acceleromyography,
      which is the most common used neuromuscular monitoring method.
Neuromuscular blocking agents (NMBAs) are frequently used in anesthesia for tracheal
      intubation, artificial ventilation, and continued muscle relaxation during surgical
      interventions. It is of particular importance to measure the neuromuscular block for several
      reasons:

        1. To monitor the onset of neuromuscular block and to intubate when deep muscular
           relaxation is attained.

        2. To choose the best antagonist and its dosage dependent of the degree of neuromuscular
           block (for instance sugammadex for deep neuromuscular block or neostigmine for
           superficial block).

        3. To avoid antagonization of neuromuscular block in the case of complete recovery of
           neuromuscular function.

      It is proven that monitoring of neuromuscular block reduces patient mortality. It avoids
      postoperative residual curarization, which is associated with complications such as
      hypoxemia, bronchoaspiration and pneumonia. Therefore the development and validation of new
      and efficacious neuromuscular monitoring devices is of great importance.

      Neuromuscular monitoring is done by stimulating with an electric current a nerve and to
      measure the response of the corresponding muscle. In clinical practice acceleromyography is
      the most often used quantitative measurement method, because it is much easier to apply than
      other established quantitative neuromuscular monitoring methods such as mechanomyograpy and
      electromyography. Acceleromyography is based on the piezoelectric effect where mechanical
      forces at play on the surfaces of certain materials, such as crystals or ceramics, induce an
      electrical current. According to Newton's second law of motion, force equals mass times
      acceleration (F=m x a). At constant mass, the acceleration measured and the voltage thereby
      generated can be used to derive the force of the stimulated muscle. It is standard practice
      to stimulate the ulnar nerve at the wrist and to measure the movement of the adductor
      pollicis. In the research setting acceleromyography (TOF Watch SX® monitor) is an established
      and widely used method. This method requires freedom of movement of the patient's thumb.
      Unfortunately this is not always possible due to the constraints of patient positioning
      during the operation. The TOF Cuff® monitor is a modified non-invasive blood pressure cuff
      that incorporates stimulating electrodes in its inner surface and is based on the stimulation
      of the peripheral nerve in the arm (brachial plexus, ulnar and median nerves principally).
      The evoked neuromuscular activity is recorded through the changes in pressure generated in
      the inner part of the cuff by the muscular activity after the stimulus. Moreover, this device
      can be used for non-invasive reading of the blood pressure. This device has been validated
      with mechanomyography, but was never been compared with acceleromyography, which is the most
      common used neuromuscular monitoring method.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Total recovery time of neuromuscular block
time frame: 60 to 120 minutes
description: The total recovery time, i.e. total duration of the neuromuscular block is defined as the time in minutes from start of injection of rocuronium until a normalized TOF ratio of 90% (Dur TOF 0.9). TOF = Train of Four
measure: Onset time
time frame: 1 to 4 minutes
description: time in seconds from start of injection of rocuronium until 95% depression of the first twitch (T1) of the TOF(Train of Four)
measure: Duration TOF count 1
time frame: 20 - 30 minutes
description: Time (in minutes) from administration of rocuronium to emergence of the 1st twitch of the TOF (Dur TOFc1)
measure: Duration TOF 25%
time frame: 30 - 40 minutes
description: Time (in minutes) from administration of rocuronium to emergence of a normalized TOF ratio of 25%
measure: Duration TOF 50%
time frame: 30 - 50 minutes
description: Time (in minutes) from administration of rocuronium to emergence of a normalized TOF ratio of 50%
measure: Duration TOF 75%
time frame: 30 - 60 minutes
description: Time (in minutes) from administration of rocuronium to emergence of a normalized TOF ratio of 75%
arm group label: Tof Watch SX and Tof Cuff
arm group type: Other
description: Patients undergoing surgery with intubation and receiving a single intubation dose of rocuronium (0.6 mg/kg) under propofol anesthesia will have monitoring of neuromuscular block with two monitors simultaneously.
intervention type: Device
intervention name: Tof cuff
description: The Tof Cuff will be installed on one arm. After anesthesia induction the Tof Cuff will be calibrated and continuos monitoring of the neuromuscular block started until complete recovery of neuromuscular block.
arm group label: Tof Watch SX and Tof Cuff
intervention type: Device
intervention name: Tof Watch SX
description: The Tof Watch SX will be installed on the opposite arm to the Tof Cuff. After anesthesia induction the Tof Watch SX will be calibrated and continuos monitoring of the neuromuscular block started until complete recovery of neuromuscular block.
arm group label: Tof Watch SX and Tof Cuff
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Christoph Czarnetzki, MD
role: Study Chair
affiliation: University Hospitals of Geneva
facility: 
country: Switzerland
url: http://www.tdx.cat/handle/10803/307220
description: Thesis for the validation of the tof cuff (in spanish)
citation: Rodiera J, Serradell A, Alvarez-Gomez JA, Aliaga L. The cuff method: a pilot study of a new method of monitoring neuromuscular function. Acta Anaesthesiol Scand. 2005 Nov;49(10):1552-8. doi: 10.1111/j.1399-6576.2005.00777.x.
PMID: 16223405
citation: Veiga Ruiz G, Garcia Cayuela J, Orozco Montes J, Parreno Caparros M, Garcia Rojo B, Aguayo Albasini JL. Monitoring intraoperative neuromuscular blockade and blood pressure with one device (TOF-Cuff): A comparative study with mechanomyography and invasive blood pressure. Rev Esp Anestesiol Reanim. 2017 Dec;64(10):560-567. doi: 10.1016/j.redar.2017.03.013. Epub 2017 Jun 27. English, Spanish.
PMID: 28662770
citation: Sfeir Machado E, Keli-Barcelos G, Dupuis-Lozeron E, Tramer MR, Czarnetzki C. Assessment of spontaneous neuromuscular recovery: A comparison of the TOF-Cuff(R) with the TOF Watch SX(R). Acta Anaesthesiol Scand. 2020 Feb;64(2):173-179. doi: 10.1111/aas.13487. Epub 2019 Oct 28.
PMID: 31593293
responsible party type: Sponsor-Investigator
investigator affiliation: University Hospital, Geneva
investigator full name: Christoph Czarnetzki
investigator title: Médecin adjoint