<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/NCT04446702</url>
  </required_header>
  <id_info>
    <org_study_id>A-BR-52120-269</org_study_id>
    <nct_id>NCT04446702</nct_id>
  </id_info>
  <brief_title>Retrospective Real-Life Study From One Brazilian Reference Center Assessing Long-Term Experience In The Treatment Of Adult Spasticity With AbobotulinumtoxinA</brief_title>
  <acronym>RETURN</acronym>
  <official_title>Retrospective Real-life Study From One Brazilian Reference Centre Assessing Long-term Experience in the Treatment of Adult Spasticity With AbobotulinumtoxinA (RETURN Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ipsen</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ipsen</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>
      The aim of the study is to describe the long-term use of abobotulinumtoxinA (Dysport®) in&#xD;
      adult subjects affected with upper limb spasticity (ULS) +/- lower limb spasticity (LLS) who&#xD;
      received treatment with Dysport® for a minimum of three injections cycles at the Instituto de&#xD;
      Medicina Física e Reabilitação do Hospital das Clínicas da Faculdade de Medicina da&#xD;
      Universidade de São Paulo (IMREA HC FMUSP) in Brazil.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 5, 2021</start_date>
  <completion_date type="Actual">December 10, 2021</completion_date>
  <primary_completion_date type="Actual">December 10, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Average total dose injected during all sessions of Dysport® in ULS +/- LLS</measure>
    <time_frame>From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Median total dose injected during all sessions of Dysport® in ULS +/- LLS</measure>
    <time_frame>From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Average interval between Dysport® injections in ULS +/- LLS</measure>
    <time_frame>From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Baseline subjects characteristics</measure>
    <time_frame>Baseline (first Dysport® injection)</time_frame>
    <description>Demography (age at first injection during the period of interest, sex, weight)&#xD;
History of spasticity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total number of Dysport® injection cycles</measure>
    <time_frame>From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total time exposure to Dysport® treatment in ULS +/- LLS</measure>
    <time_frame>From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total dose injected per cycle, per limb, per muscle and overall</measure>
    <time_frame>From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of muscles injected in ULS +/- LLS</measure>
    <time_frame>From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reported reason for Dysport® injection and for change</measure>
    <time_frame>From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)</time_frame>
    <description>Outcome will be assessed according following reasons: due to medical need, unplanned need and not recorded</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Dysport® interruptions</measure>
    <time_frame>From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reasons of Dysport® discontinuation</measure>
    <time_frame>From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019).</time_frame>
    <description>Outcome will be assessed according following reasons: side effects (e.g. excessive weakness, hematoma), contractures, absence of clinical response, long lasting clinical improvement, patient lost follow up and other.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Modified Ashworth Scale (MAS) scores by time period per muscle</measure>
    <time_frame>From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)</time_frame>
    <description>The MAS is a six-point scale to grade muscle tone in the injected muscle from 0 (no increase in tone) to 4 (affected parts rigid in flexion or extension). Upper limb: shoulder abduction, elbow flexion, elbow extension, wrist flexion, wrist extension and fingers flexion. Lower limb: hip flexion, hip adduction, hip abduction, knee flexion, knee extension, ankle dorsiflexion and ankle plantar flexion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Functional Independence Measure (FIM) subscales</measure>
    <time_frame>From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)</time_frame>
    <description>Subscales and total scores of FIM will be measured. The FIM is a method for categorising patients on a seven-point scale (range 1 to 7). It comprises of 18 items, grouped into 2 subscales (motor and cognition). The motor subscale includes: eating, grooming, bathing, dressing upper body, dressing lower body, toileting, bladder management, bowel management, transfers - bed/chair/wheelchair, transfers - toilet, transfers - bath/shower, walk/wheelchair and stairs. The cognition subscale includes: comprehension, expression, social interaction, problem solving and memory. The Scores are summed to obtain a total score that can range between 18 and 126.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Pain score according to pain Visual Analogue Scales (VAS)</measure>
    <time_frame>From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)</time_frame>
    <description>The pain Visual Analogue Scale (VAS) is a numeric graphic rating scale (NGRS) of self-reported symptoms. Scores are recorded as whole numbers between zero and 10, where zero indicates no pain symptom at all, and 10 indicates a as bad as it could be.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gait pattern evaluation in patients with LLS</measure>
    <time_frame>From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)</time_frame>
    <description>Gait Pattern Modification in patients with LLS is based on physician´s clinical evaluation and it will be evaluated for each lower limb (left and right) or both according to pre-specified patterns: equinismus, foot inversion, knee hyperextension, adduction, mowing abduction, thigh elevation, hip elevation, false trendelenburg, not able to walk. The Gait Pattern Improvement is described based on patient´s perception of gait. The patients respond Yes or No and if Yes the % of improvement is replied</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concomitant drugs for the management of patients with ULS +/- LLS</measure>
    <time_frame>From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)</time_frame>
    <description>List the systemic drug therapies, including: antispasticity medications (e.g. Baclofen, Tizanidin, Dantrolene), simple pain medications (e.g. paracetamol or NSAIDS), neuropathic pain and spasticity medications (e.g. Gabapentin, Pregabalin, Amitriptyline), opioids, phenol, alcool or other neurolytic agents.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Non-drug concomitant therapies for the management of patients with ULS +/- LLS</measure>
    <time_frame>From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)</time_frame>
    <description>List the non-drug concomitant therapies, including occupational therapy, physiotherapy and others (e.g.: orthotics, serial casting, splinting, electric stimulation)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and intensity of Adverse Events</measure>
    <time_frame>From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)</time_frame>
    <description>Adverse events will be assessed according to incidence, intensity/grade (mild, moderate and severe), causality (related and not related to the product), outcome (the overall association between an exposure to a drug and an outcome) and action taken. All Adverse Events (AEs) (including fatal events and Serious Adverse Events (SAEs)) and special situation (pregnancy, overdose, off-label use) will be reported with the number and proportion of events. The incidence will be provided and classified by System Organ Class and Preferred Term</description>
  </secondary_outcome>
  <enrollment type="Actual">200</enrollment>
  <condition>Spasticity</condition>
  <eligibility>
    <study_pop>
      <textblock>
        All eligible adult patients having received Dysport® for at least three cycles for the&#xD;
        treatment of ULS +/- LLS between January 1st, 2006 and July 31st, 2019 at Instituto de&#xD;
        Medicina Física e Reabilitação do Hospital das Clínicas da Faculdade de Medicina da&#xD;
        Universidade de São Paulo (IMREA HC FMUSP) in Brazil with pre- and post-injection&#xD;
        effectiveness data available will be enrolled.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult aged ≥18 years old at the time of the first Dysport® injection&#xD;
&#xD;
          -  Diagnosed with spasticity&#xD;
&#xD;
          -  Treated with a minimum of three Dysport® injection cycles for ULS +/- LLS in the&#xD;
             observational period&#xD;
&#xD;
          -  Follow up effectiveness data are available in the subject's medical record&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients have received previous treatment with another BoNT-A less than 12 weeks prior&#xD;
             to the patient data collection in the study&#xD;
&#xD;
          -  Adults with cerebral palsy&#xD;
&#xD;
          -  Patients treated with BoNT-A in a clinical trial setting&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ipsen Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Ipsen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Instituto de Medicina Física e Reabilitação do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (IMREA HC FMUSP)</name>
      <address>
        <city>San Paolo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>June 8, 2020</study_first_submitted>
  <study_first_submitted_qc>June 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 25, 2020</study_first_posted>
  <last_update_submitted>December 15, 2021</last_update_submitted>
  <last_update_submitted_qc>December 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Muscle Spasticity</mesh_term>
  </condition_browse>
  <!-- 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/NCT04446702
org study id: A-BR-52120-269
nct id: NCT04446702
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The aim of the study is to describe the long-term use of abobotulinumtoxinA (Dysport®) in
      adult subjects affected with upper limb spasticity (ULS) +/- lower limb spasticity (LLS) who
      received treatment with Dysport® for a minimum of three injections cycles at the Instituto de
      Medicina Física e Reabilitação do Hospital das Clínicas da Faculdade de Medicina da
      Universidade de São Paulo (IMREA HC FMUSP) in Brazil.
observational model: Cohort
time perspective: Retrospective
measure: Average total dose injected during all sessions of Dysport® in ULS +/- LLS
time frame: From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)
measure: Median total dose injected during all sessions of Dysport® in ULS +/- LLS
time frame: From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)
measure: Average interval between Dysport® injections in ULS +/- LLS
time frame: From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)
measure: Baseline subjects characteristics
time frame: Baseline (first Dysport® injection)
description: Demography (age at first injection during the period of interest, sex, weight)
History of spasticity
measure: Total number of Dysport® injection cycles
time frame: From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)
measure: Total time exposure to Dysport® treatment in ULS +/- LLS
time frame: From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)
measure: Total dose injected per cycle, per limb, per muscle and overall
time frame: From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)
measure: Number of muscles injected in ULS +/- LLS
time frame: From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)
measure: Reported reason for Dysport® injection and for change
time frame: From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)
description: Outcome will be assessed according following reasons: due to medical need, unplanned need and not recorded
measure: Number of Dysport® interruptions
time frame: From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)
measure: Reasons of Dysport® discontinuation
time frame: From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019).
description: Outcome will be assessed according following reasons: side effects (e.g. excessive weakness, hematoma), contractures, absence of clinical response, long lasting clinical improvement, patient lost follow up and other.
measure: Changes in Modified Ashworth Scale (MAS) scores by time period per muscle
time frame: From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)
description: The MAS is a six-point scale to grade muscle tone in the injected muscle from 0 (no increase in tone) to 4 (affected parts rigid in flexion or extension). Upper limb: shoulder abduction, elbow flexion, elbow extension, wrist flexion, wrist extension and fingers flexion. Lower limb: hip flexion, hip adduction, hip abduction, knee flexion, knee extension, ankle dorsiflexion and ankle plantar flexion.
measure: Changes in Functional Independence Measure (FIM) subscales
time frame: From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)
description: Subscales and total scores of FIM will be measured. The FIM is a method for categorising patients on a seven-point scale (range 1 to 7). It comprises of 18 items, grouped into 2 subscales (motor and cognition). The motor subscale includes: eating, grooming, bathing, dressing upper body, dressing lower body, toileting, bladder management, bowel management, transfers - bed/chair/wheelchair, transfers - toilet, transfers - bath/shower, walk/wheelchair and stairs. The cognition subscale includes: comprehension, expression, social interaction, problem solving and memory. The Scores are summed to obtain a total score that can range between 18 and 126.
measure: Changes in Pain score according to pain Visual Analogue Scales (VAS)
time frame: From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)
description: The pain Visual Analogue Scale (VAS) is a numeric graphic rating scale (NGRS) of self-reported symptoms. Scores are recorded as whole numbers between zero and 10, where zero indicates no pain symptom at all, and 10 indicates a as bad as it could be.
measure: Gait pattern evaluation in patients with LLS
time frame: From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)
description: Gait Pattern Modification in patients with LLS is based on physician´s clinical evaluation and it will be evaluated for each lower limb (left and right) or both according to pre-specified patterns: equinismus, foot inversion, knee hyperextension, adduction, mowing abduction, thigh elevation, hip elevation, false trendelenburg, not able to walk. The Gait Pattern Improvement is described based on patient´s perception of gait. The patients respond Yes or No and if Yes the % of improvement is replied
measure: Concomitant drugs for the management of patients with ULS +/- LLS
time frame: From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)
description: List the systemic drug therapies, including: antispasticity medications (e.g. Baclofen, Tizanidin, Dantrolene), simple pain medications (e.g. paracetamol or NSAIDS), neuropathic pain and spasticity medications (e.g. Gabapentin, Pregabalin, Amitriptyline), opioids, phenol, alcool or other neurolytic agents.
measure: Non-drug concomitant therapies for the management of patients with ULS +/- LLS
time frame: From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)
description: List the non-drug concomitant therapies, including occupational therapy, physiotherapy and others (e.g.: orthotics, serial casting, splinting, electric stimulation)
measure: Incidence and intensity of Adverse Events
time frame: From baseline (visit 1) and up to the last injection during data record (January 1st, 2006 to July 31st, 2019)
description: Adverse events will be assessed according to incidence, intensity/grade (mild, moderate and severe), causality (related and not related to the product), outcome (the overall association between an exposure to a drug and an outcome) and action taken. All Adverse Events (AEs) (including fatal events and Serious Adverse Events (SAEs)) and special situation (pregnancy, overdose, off-label use) will be reported with the number and proportion of events. The incidence will be provided and classified by System Organ Class and Preferred Term
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Ipsen Medical Director
role: Study Director
affiliation: Ipsen
facility: 
country: Brazil
responsible party type: Sponsor
mesh term: Muscle Spasticity