<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/NCT03259204</url>
  </required_header>
  <id_info>
    <org_study_id>2017-00202</org_study_id>
    <nct_id>NCT03259204</nct_id>
  </id_info>
  <brief_title>Swedish Multicenter Trial of Outpatient Prevention of Leg Clots</brief_title>
  <acronym>StopLegClots</acronym>
  <official_title>Prevention of Thromboembolism and Failed Healing During Lower Limb Immobilization - Multicenter Study With Adjuvant Intermittent Pneumatic Compression Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Karolinska University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Sahlgrenska University Hospital, Sweden</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Danderyd Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Stockholm South General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Uppsala University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Gävle Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Höglandssjukhuset Eksjö</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Norrtälje Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Östersund Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Helsingborgs Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Uddevalla Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Norra Älvsborgs Länssjukhus</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Istituto Ortopedico Rizzoli</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Lugano Regional Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Alingsås Lasarett</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital, Akershus</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Karolinska University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Lower limb immobilization is associated with high risk of complications, i.e. venous&#xD;
      thromboembolism (VTE) and failed healing. Pharmacoprophylaxis of VTE is in leg-immobilized&#xD;
      patients, however, low- or non-effective and associated with adverse events. Thus, there is a&#xD;
      need for novel treatments.&#xD;
&#xD;
      This study aims to demonstrate in leg immobilized patients who have suffered an ankle&#xD;
      fracture (1000 patients) or an Achilles tendon rupture (400 patients) that adjuvant&#xD;
      intermittent pneumatic compression (IPC) therapy, which targets impaired vascular flow,&#xD;
      compared to treatment-as-usual with plaster cast, reduces VTE incidence and improves healing.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The proposed intervention, intermittent pneumatic compression (IPC) is an evidence-based&#xD;
      prevention for VTE in hospitalized patients and used in daily practice. IPC is, however, not&#xD;
      currently used on outpatients and it is currently unknown if it reduces the risk of VTE&#xD;
      during long term leg-immobilization. Plaster cast and orthosis treatments are currently used&#xD;
      in daily practice on Achilles tendon ruptures and ankle fractures. At present there is no&#xD;
      consensus about using VTE prophylaxis in leg-immobilized patients. Since pharmacoprophylaxis&#xD;
      has shown low- or no VTE preventive effects in leg-immobilization, is not recommended by some&#xD;
      guidelines.&#xD;
&#xD;
      Furthermore, since all patients will undergo clinical examinations and have DVT-screening&#xD;
      performed with compression Doppler ultrasound (CDU) removal of leg immobilization this will&#xD;
      comprise an extra security for the included patients to detect a VTE. If a VTE is detected&#xD;
      clinical guidelines will be followed by initiating chemical VTE-treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 1, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2024</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>Prevention</primary_purpose>
    <masking>Double (Care Provider, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Venous Thromboembolic Events (VTE)</measure>
    <time_frame>Up til the time of removal of leg immobilization, approx. 6-8 weeks</time_frame>
    <description>The primary outcome is VTE defined as symptomatic Deep venous Thrombosis (DVT) or asymptomatic DVTs,or symptomatic pulmonary embolism</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Patient reported Outcome - ATRS</measure>
    <time_frame>6 months and 1 year</time_frame>
    <description>symptoms will be assessed using the reliable and valid score; the Achilles tendon Total Rupture Score (ATRS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient reported Outcome - FAOS</measure>
    <time_frame>6 months and 1 year</time_frame>
    <description>symptoms will be assessed using the reliable and valid score; the Foot and Ankle Outcome Score (FAOS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient reported Outcome - OMAS</measure>
    <time_frame>6 months and 1 year</time_frame>
    <description>symptoms will be assessed using the reliable and valid score; the Olerud-Molander Ankle Score (OMAS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient reported Outcome - EQ-5D-5L</measure>
    <time_frame>6 months and 1 year</time_frame>
    <description>symptoms will be assessed using the reliable and valid score; EuroQol Group's questionnaire (EQ-5D-5L).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional outcome - muscular endurance tests (heel-rise)</measure>
    <time_frame>1 year</time_frame>
    <description>Patient leg function will be measured by a validated endurance test (i.e. the heel-rise test) at 1 year post-injury.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Callus production</measure>
    <time_frame>6 weeks</time_frame>
    <description>Microdialysis followed by quantification of procollagens will assess callus production in Achilles tendon healing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>VTE-preventive mechanisms</measure>
    <time_frame>6 weeks</time_frame>
    <description>VTE-preventive mechanisms will be analyzed at the 6 week visit by assessments of profibrinolysis and coagulation factors as well as by blood-flow quantification .</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of VTE in patients using low molecular weight heparin(LMWH) with or without adjvant IPC</measure>
    <time_frame>6-8 weeks</time_frame>
    <description>Efficacy of LMWH with and without the use of IPC as to prevent VTE will be studied in order to confirm the efficency of a commonly used drug for VTE prophylaxis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient mortality</measure>
    <time_frame>1year and 2 years</time_frame>
    <description>Mortality of patients included will be recorded and investigated for cause of death. If the cause of death is VTE, this will be reported. The overall mortality rate in this study is expected to be low. Mortality will be investigated via patient journals at one year after study inclusion, and at 2 years via national mortality register.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health economic analyses</measure>
    <time_frame>2 years</time_frame>
    <description>Together with Karolinska Institutet, LIME, the trial treatment effects will involve a within-trial evaluation of cost effectiveness integrated into a decision-analytic model of longer run costs and health effects</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">1400</enrollment>
  <condition>Achilles Tendon Rupture</condition>
  <condition>Ankle Fractures</condition>
  <condition>Venous Thromboembolism</condition>
  <arm_group>
    <arm_group_label>Leg Immobilization</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Routine care include that the lower limb will be immobilized in an orthosis or a below-knee plaster cast according to local routines.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Adjuvant IPC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Leg Immobilization with the addition of IPC. Patients will during lower limb immobilization receive bilateral calf IPC.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Adjuvant IPC</intervention_name>
    <description>This IPC-system delivers sequential circumferential compression. The IPC device is mobile and should therefore not restrict patient mobilization, but can be taken off if the patient wants to mobilize independently.</description>
    <arm_group_label>Adjuvant IPC</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Acute unilateral Achilles tendon rupture or isolated Ankle Fracture&#xD;
&#xD;
          -  Treatment starts within 10 days in a hospital setting&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability or refusal to give informed consent for participation in the study&#xD;
&#xD;
          -  Inability to comply with the study instructions&#xD;
&#xD;
          -  Known kidney disorder&#xD;
&#xD;
          -  Heart failure with pitting oedema&#xD;
&#xD;
          -  Presence of known malignancy&#xD;
&#xD;
          -  Current bleeding disorder&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Planned follow-up at another hospital&#xD;
&#xD;
          -  Pilon fracture&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paul W Ackermann, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Karolinska University Hospital, 171 76 Stockholm, SWEDEN</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Luigi Belcastro, RN</last_name>
    <phone>+46724641144</phone>
    <email>luigi.belcastro@sll.se</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Simon Svedman, MD</last_name>
    <email>Simon.svedman@ki.se</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Karolinska University Hospital</name>
      <address>
        <city>Stockholm</city>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Simon Svedman, MD</last_name>
      <email>Simon.svedman@ki.se</email>
    </contact>
    <contact_backup>
      <last_name>Luigi Belcastro, RN</last_name>
      <phone>+46724641144</phone>
      <email>luigi.belcastro@sll.se</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <link>
    <url>http://ki.se/mmk/stop-leg-clots</url>
    <description>Official study site</description>
  </link>
  <reference>
    <citation>Arverud ED, Anundsson P, Hardell E, Barreng G, Edman G, Latifi A, Labruto F, Ackermann PW. Ageing, deep vein thrombosis and male gender predict poor outcome after acute Achilles tendon rupture. Bone Joint J. 2016 Dec;98-B(12):1635-1641. doi: 10.1302/0301-620X.98B12.BJJ-2016-0008.R1.</citation>
    <PMID>27909125</PMID>
  </reference>
  <reference>
    <citation>Domeij-Arverud E, Ackermann PW. Deep Venous Thrombosis and Tendon Healing. Adv Exp Med Biol. 2016;920:221-8. doi: 10.1007/978-3-319-33943-6_21.</citation>
    <PMID>27535264</PMID>
  </reference>
  <reference>
    <citation>Domeij-Arverud E, Labruto F, Latifi A, Nilsson G, Edman G, Ackermann PW. Intermittent pneumatic compression reduces the risk of deep vein thrombosis during post-operative lower limb immobilisation: a prospective randomised trial of acute ruptures of the Achilles tendon. Bone Joint J. 2015 May;97-B(5):675-80. doi: 10.1302/0301-620X.97B5.34581.</citation>
    <PMID>25922463</PMID>
  </reference>
  <reference>
    <citation>Abdul Alim M, Domeij-Arverud E, Nilsson G, Edman G, Ackermann PW. Achilles tendon rupture healing is enhanced by intermittent pneumatic compression upregulating collagen type I synthesis. Knee Surg Sports Traumatol Arthrosc. 2018 Jul;26(7):2021-2029. doi: 10.1007/s00167-017-4621-8. Epub 2017 Jul 1.</citation>
    <PMID>28668970</PMID>
  </reference>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>August 16, 2017</study_first_submitted>
  <study_first_submitted_qc>August 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 23, 2017</study_first_posted>
  <last_update_submitted>January 3, 2023</last_update_submitted>
  <last_update_submitted_qc>January 3, 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>Karolinska University Hospital</investigator_affiliation>
    <investigator_full_name>Paul Ackermann</investigator_full_name>
    <investigator_title>Professor, MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Achilles tendon</keyword>
  <keyword>Microdialysis</keyword>
  <keyword>Immobilization</keyword>
  <keyword>Wound healing</keyword>
  <keyword>Intermittent Pneumatic Compression</keyword>
  <keyword>Ultrasonography</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thromboembolism</mesh_term>
    <mesh_term>Venous Thromboembolism</mesh_term>
    <mesh_term>Rupture</mesh_term>
    <mesh_term>Ankle Fractures</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 1, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/04/NCT03259204/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03259204
org study id: 2017-00202
nct id: NCT03259204
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Lower limb immobilization is associated with high risk of complications, i.e. venous
      thromboembolism (VTE) and failed healing. Pharmacoprophylaxis of VTE is in leg-immobilized
      patients, however, low- or non-effective and associated with adverse events. Thus, there is a
      need for novel treatments.

      This study aims to demonstrate in leg immobilized patients who have suffered an ankle
      fracture (1000 patients) or an Achilles tendon rupture (400 patients) that adjuvant
      intermittent pneumatic compression (IPC) therapy, which targets impaired vascular flow,
      compared to treatment-as-usual with plaster cast, reduces VTE incidence and improves healing.
The proposed intervention, intermittent pneumatic compression (IPC) is an evidence-based
      prevention for VTE in hospitalized patients and used in daily practice. IPC is, however, not
      currently used on outpatients and it is currently unknown if it reduces the risk of VTE
      during long term leg-immobilization. Plaster cast and orthosis treatments are currently used
      in daily practice on Achilles tendon ruptures and ankle fractures. At present there is no
      consensus about using VTE prophylaxis in leg-immobilized patients. Since pharmacoprophylaxis
      has shown low- or no VTE preventive effects in leg-immobilization, is not recommended by some
      guidelines.

      Furthermore, since all patients will undergo clinical examinations and have DVT-screening
      performed with compression Doppler ultrasound (CDU) removal of leg immobilization this will
      comprise an extra security for the included patients to detect a VTE. If a VTE is detected
      clinical guidelines will be followed by initiating chemical VTE-treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Care Provider, Outcomes Assessor)
measure: Venous Thromboembolic Events (VTE)
time frame: Up til the time of removal of leg immobilization, approx. 6-8 weeks
description: The primary outcome is VTE defined as symptomatic Deep venous Thrombosis (DVT) or asymptomatic DVTs,or symptomatic pulmonary embolism
measure: Patient reported Outcome - ATRS
time frame: 6 months and 1 year
description: symptoms will be assessed using the reliable and valid score; the Achilles tendon Total Rupture Score (ATRS)
measure: Patient reported Outcome - FAOS
time frame: 6 months and 1 year
description: symptoms will be assessed using the reliable and valid score; the Foot and Ankle Outcome Score (FAOS)
measure: Patient reported Outcome - OMAS
time frame: 6 months and 1 year
description: symptoms will be assessed using the reliable and valid score; the Olerud-Molander Ankle Score (OMAS)
measure: Patient reported Outcome - EQ-5D-5L
time frame: 6 months and 1 year
description: symptoms will be assessed using the reliable and valid score; EuroQol Group's questionnaire (EQ-5D-5L).
measure: Functional outcome - muscular endurance tests (heel-rise)
time frame: 1 year
description: Patient leg function will be measured by a validated endurance test (i.e. the heel-rise test) at 1 year post-injury.
measure: Callus production
time frame: 6 weeks
description: Microdialysis followed by quantification of procollagens will assess callus production in Achilles tendon healing.
measure: VTE-preventive mechanisms
time frame: 6 weeks
description: VTE-preventive mechanisms will be analyzed at the 6 week visit by assessments of profibrinolysis and coagulation factors as well as by blood-flow quantification .
measure: Incidence of VTE in patients using low molecular weight heparin(LMWH) with or without adjvant IPC
time frame: 6-8 weeks
description: Efficacy of LMWH with and without the use of IPC as to prevent VTE will be studied in order to confirm the efficency of a commonly used drug for VTE prophylaxis.
measure: Patient mortality
time frame: 1year and 2 years
description: Mortality of patients included will be recorded and investigated for cause of death. If the cause of death is VTE, this will be reported. The overall mortality rate in this study is expected to be low. Mortality will be investigated via patient journals at one year after study inclusion, and at 2 years via national mortality register.
measure: Health economic analyses
time frame: 2 years
description: Together with Karolinska Institutet, LIME, the trial treatment effects will involve a within-trial evaluation of cost effectiveness integrated into a decision-analytic model of longer run costs and health effects
arm group label: Leg Immobilization
arm group type: No Intervention
description: Routine care include that the lower limb will be immobilized in an orthosis or a below-knee plaster cast according to local routines.
arm group label: Adjuvant IPC
arm group type: Experimental
description: Leg Immobilization with the addition of IPC. Patients will during lower limb immobilization receive bilateral calf IPC.
intervention type: Device
intervention name: Adjuvant IPC
description: This IPC-system delivers sequential circumferential compression. The IPC device is mobile and should therefore not restrict patient mobilization, but can be taken off if the patient wants to mobilize independently.
arm group label: Adjuvant IPC
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Paul W Ackermann, MD, PhD
role: Principal Investigator
affiliation: Karolinska University Hospital, 171 76 Stockholm, SWEDEN
last name: Luigi Belcastro, RN
phone: +46724641144
email: luigi.belcastro@sll.se
last name: Simon Svedman, MD
email: Simon.svedman@ki.se
facility: 
status: Recruiting
contact: 
contact backup: 
country: Sweden
url: http://ki.se/mmk/stop-leg-clots
description: Official study site
citation: Arverud ED, Anundsson P, Hardell E, Barreng G, Edman G, Latifi A, Labruto F, Ackermann PW. Ageing, deep vein thrombosis and male gender predict poor outcome after acute Achilles tendon rupture. Bone Joint J. 2016 Dec;98-B(12):1635-1641. doi: 10.1302/0301-620X.98B12.BJJ-2016-0008.R1.
PMID: 27909125
citation: Domeij-Arverud E, Ackermann PW. Deep Venous Thrombosis and Tendon Healing. Adv Exp Med Biol. 2016;920:221-8. doi: 10.1007/978-3-319-33943-6_21.
PMID: 27535264
citation: Domeij-Arverud E, Labruto F, Latifi A, Nilsson G, Edman G, Ackermann PW. Intermittent pneumatic compression reduces the risk of deep vein thrombosis during post-operative lower limb immobilisation: a prospective randomised trial of acute ruptures of the Achilles tendon. Bone Joint J. 2015 May;97-B(5):675-80. doi: 10.1302/0301-620X.97B5.34581.
PMID: 25922463
citation: Abdul Alim M, Domeij-Arverud E, Nilsson G, Edman G, Ackermann PW. Achilles tendon rupture healing is enhanced by intermittent pneumatic compression upregulating collagen type I synthesis. Knee Surg Sports Traumatol Arthrosc. 2018 Jul;26(7):2021-2029. doi: 10.1007/s00167-017-4621-8. Epub 2017 Jul 1.
PMID: 28668970
responsible party type: Principal Investigator
investigator affiliation: Karolinska University Hospital
investigator full name: Paul Ackermann
investigator title: Professor, MD, PhD
mesh term: Thromboembolism
mesh term: Venous Thromboembolism
mesh term: Rupture
mesh term: Ankle Fractures
sharing ipd: Undecided
provided document: 