xml: <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/NCT06014242</url>
    </required_header>
    <id_info>
      <org_study_id>Pro2021-0681</org_study_id>
      <nct_id>NCT06014242</nct_id>
    </id_info>
    <brief_title>Peripheral Microvascular Resistance as a Predictor for Limb Salvage</brief_title>
    <official_title>Peripheral Microvascular Resistance as a Predictor for Limb Salvage in Post-Intervention Critical Limb Ischemia Patients</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Hackensack Meridian Health</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Abbott Medical Devices</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Hackensack Meridian Health</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>Yes</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        Salvaging a threatened limb is the key therapeutic objective for patients with critical limb&#xD;
        ischemia, and the achievement of limb salvage is an independent predictor of patient&#xD;
        morbidity and mortality. Despite successful primary endovascular or surgical intervention,&#xD;
        the corresponding symptoms of rest pain and/or non-healing ulceration in some patients may&#xD;
        continue, and amputation in these patients is unavoidable. We hypothesize that the functional&#xD;
        integrity of the peripheral vascular microcirculation may be impaired in these patients.&#xD;
        However, there are currently no techniques that allow direct quantification and visualization&#xD;
        of the microcirculation due to the micro-vessel invisibility under angiography.&#xD;
  &#xD;
        In the coronary circulation, coronary flow reserve (CFR) indicates the capacity for maximal&#xD;
        hyperemic blood flow and reveals impaired coronary microvascular function (Mcginn 1990,&#xD;
        Nahser 1995). Studies have shown the clinical significance of measuring microvascular&#xD;
        resistance to predict myocardial salvage after myocardial infarction (Payne, 2012). We are&#xD;
        interested in whether this concept of coronary flow reserve can be applied peripherally to&#xD;
        patients with critical limb ischemia in order to determine whether measuring peripheral&#xD;
        vascular flow reserve can determine the integrity of the microcirculation to predict limb&#xD;
        salvage after endovascular intervention.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">September 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">September 1, 2025</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>Diagnostic</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Efficacy of the peripheral flow reserve</measure>
      <time_frame>6 months post-endovascular intervention</time_frame>
      <description>To assess whether peripheral flow reserve can predict the success rate of limb salvage in critical limb ischemia patients after endovascular intervention. Assessed by any amputation (major or minor) at 6 months post-endovascular intervention.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Symptom resolution - Ulcer healing (1m)</measure>
      <time_frame>1 month post-endovascular intervention</time_frame>
      <description>Ulcer healing: changes in the number and extent of leg ulcers compared to baseline.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Symptom resolution - Ulcer healing (6m)</measure>
      <time_frame>6 months post-endovascular intervention</time_frame>
      <description>Ulcer healing: changes in the number and extent of leg ulcers compared to baseline.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Symptom resolution - Pain (1m)</measure>
      <time_frame>1 month post-endovascular intervention</time_frame>
      <description>Resolution of rest pain and alteration in visual analogue pain compared to baseline.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Symptom resolution - Pain (6m)</measure>
      <time_frame>6 months post-endovascular intervention</time_frame>
      <description>Resolution of rest pain and alteration in visual analogue pain compared to baseline.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Ankle-brachial index (ABI) (1m)</measure>
      <time_frame>1 month post-endovascular intervention</time_frame>
      <description>Improvement in Ankle-brachial index (ABI) compared to baseline.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Ankle-brachial index (ABI) (6m)</measure>
      <time_frame>6 months post-endovascular intervention</time_frame>
      <description>Improvement in Ankle-brachial index (ABI) compared to baseline.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Toe-brachial index (TBI) (1m)</measure>
      <time_frame>1 month post-endovascular intervention</time_frame>
      <description>Improvement in Toe-brachial index (TBI) compared to baseline.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Toe-brachial index (TBI) (6m)</measure>
      <time_frame>6 months post-endovascular intervention</time_frame>
      <description>Improvement in Toe-brachial index (TBI) compared to baseline.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rutherford classification (1m)</measure>
      <time_frame>1 month post-endovascular intervention</time_frame>
      <description>Use of The Rutherford classification to assess peripheral artery disease compared to baseline. A 7 category scale is being used with 0 being Asymptomatic and 6 being Ulceration or gangrene.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rutherford classification (6m)</measure>
      <time_frame>6 months post-endovascular intervention</time_frame>
      <description>Use of The Rutherford classification to assess peripheral artery disease compared to baseline. A 7 category scale is being used with 0 being Asymptomatic and 6 being Ulceration or gangrene.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Transcutaneous oxygen partial pressure (TcPO2) (1m)</measure>
      <time_frame>1 month post-endovascular intervention</time_frame>
      <description>Transcutaneous partial pressure of oxygen (TcPO2) will be measured representing the amount of oxygen diffusing outward across the skin (used as a surrogate for arterial perfusion).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Transcutaneous oxygen partial pressure (TcPO2) (6m)</measure>
      <time_frame>6 months post-endovascular intervention</time_frame>
      <description>Transcutaneous partial pressure of oxygen (TcPO2) will be measured representing the amount of oxygen diffusing outward across the skin (used as a surrogate for arterial perfusion).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Target lesion revascularization (1m)</measure>
      <time_frame>At 1 month post-endovascular intervention</time_frame>
      <description>Need for revascularization (yes/no)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Target lesion revascularization (6m)</measure>
      <time_frame>At 6 month post-endovascular intervention</time_frame>
      <description>Need for revascularization (yes/no)</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">40</enrollment>
    <condition>Peripheral Arterial Disease</condition>
    <arm_group>
      <arm_group_label>Peripheral vascular flow reserve measurement</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Post-procedure peripheral vascular flow reserve by thermodilution will be measured by the pressure wire.</description>
    </arm_group>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Peripheral vascular flow reserve measurement</intervention_name>
      <description>Peripheral arterial (below knee popliteal and above the level of ankle distal tibial) thermodilution curves will be obtained. One of the distal tibial arteries (anterior tibial, posterior tibial or peroneal artery, whichever reaches the most distal part of the foot in the run off) will be picked for measurements. At room temperature, 3 ml of saline will be injected brisk manually to determine the peak arterial flow, presented as mean transit time (Tmn). Resting Tmn will be performed and averaged by triplicate measurements at baseline. Then maximal hyperemia will be induced by intra-arterial injection of 30 mg papaverine through the guiding catheter, then 3 ml of saline will be injected to get hyperemic Tmn averaged by triplicate measurements. The guidewire will be kept in a fixed position during the series of measurements. Peripheral vascular flow reserve was calculated as resting Tmn divided by hyperemic Tmn (Fukunaga 2015).</description>
      <arm_group_label>Peripheral vascular flow reserve measurement</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Chronic critical limb ischemia (Rutherford 4-6).&#xD;
  &#xD;
            -  Age ≥18 years&#xD;
  &#xD;
            -  Ability and willingness to sign the IRB approved Informed Consent form&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Non-reconstructable chronic total occlusive disease of the proximal inflow vessels&#xD;
               that would make flow reserve measurements impossible.&#xD;
  &#xD;
            -  Non-salvageable lower extremity due to infection or overwhelming per-existing tissue&#xD;
               loss (most critical Rutherford 6 patients).&#xD;
  &#xD;
            -  Inability to understand the study or a history of non-compliance with medical advice;&#xD;
  &#xD;
            -  History of any cognitive or mental health status that would interfere with study&#xD;
               participation;&#xD;
  &#xD;
            -  Currently enrolled in any pre-approval investigational study.&#xD;
  &#xD;
            -  Female subjects who are pregnant or nursing or planning to become pregnant within the&#xD;
               study period;&#xD;
  &#xD;
            -  Known sensitivity to contrast media, which can't be adequately pre-medicated;&#xD;
  &#xD;
            -  Expected life span less than 6 months.&#xD;
  &#xD;
            -  Unable to read/understand/sign the English Language consent form&#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>David O'Connor, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Hackensack Meridian Health</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Patricia Arakelian, RN</last_name>
      <phone>5519962000</phone>
      <phone_ext>5722</phone_ext>
      <email>patricia.arakelian@hmhn.org</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Stephanie Lynes, RN</last_name>
      <phone>5519962000</phone>
      <phone_ext>5595</phone_ext>
      <email>Stephanie.Lynes@hmhn.org</email>
    </overall_contact_backup>
    <reference>
      <citation>McGinn, A.L., White, C.W. and Wilson, R.F., 1990. Interstudy variability of coronary flow reserve. Influence of heart rate, arterial pressure, and ventricular preload. Circulation, 81(4), pp.1319-1330. Nahser Jr, P.J., Brown, R.E., Oskarsson, H., Winniford, M.D. and Rossen, J.D., 1995. Maximal coronary flow reserve and metabolic coronary vasodilation in patients with diabetes mellitus. Circulation, 91(3), pp.635-640. Payne, A.R., Berry, C., Doolin, O., McEntegart, M., Petrie, M.C., Lindsay, M.M., Hood, S., Carrick, D., Tzemos, N., Weale, P. and McComb, C., 2012. Microvascular resistance predicts myocardial salvage and infarct characteristics in ST-elevation myocardial infarction. Journal of the American Heart Association, 1(4), p.e002246. Camici, P.G., d'Amati, G. and Rimoldi, O., 2015. Coronary microvascular dysfunction: mechanisms and functional assessment. Nature Reviews Cardiology, 12(1), p.48.</citation>
    </reference>
    <reference>
      <citation>Fukunaga M, Fujii K, Kawasaki D, Nishimura M, Horimatsu T, Saita T, Miki K, Tamaru H, Imanaka T, Naito Y, Masuyama T. Vascular flow reserve immediately after infrapopliteal intervention as a predictor of wound healing in patients with foot tissue loss. Circ Cardiovasc Interv. 2015 Jun;8(6):e002412. doi: 10.1161/CIRCINTERVENTIONS.115.002412.</citation>
      <PMID>26019143</PMID>
    </reference>
    <reference>
      <citation>Crea, F., Lanza, G.A. and Camici, P.G., 2014. Mechanisms of coronary microvascular dysfunction. In Coronary Microvascular Dysfunction (pp. 31-47). Springer, Milano.</citation>
    </reference>
    <reference>
      <citation>Pijls NH, De Bruyne B, Smith L, Aarnoudse W, Barbato E, Bartunek J, Bech GJ, Van De Vosse F. Coronary thermodilution to assess flow reserve: validation in humans. Circulation. 2002 May 28;105(21):2482-6. doi: 10.1161/01.cir.0000017199.09457.3d.</citation>
      <PMID>12034653</PMID>
    </reference>
    <reference>
      <citation>Kern MJ. Coronary physiology revisited : practical insights from the cardiac catheterization laboratory. Circulation. 2000 Mar 21;101(11):1344-51. doi: 10.1161/01.cir.101.11.1344.</citation>
      <PMID>10725297</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 21, 2023</study_first_submitted>
    <study_first_submitted_qc>August 21, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 28, 2023</study_first_posted>
    <last_update_submitted>August 21, 2023</last_update_submitted>
    <last_update_submitted_qc>August 21, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 28, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Microvascular disease</keyword>
    <keyword>Microvascular Resistance</keyword>
    <keyword>Limb Salvage</keyword>
    <keyword>Peripheral Arterial Disease</keyword>
    <keyword>critical limb ischemia</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Peripheral Arterial Disease</mesh_term>
      <mesh_term>Peripheral Vascular Diseases</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06014242
  org study id: Pro2021-0681
  nct id: NCT06014242
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: Yes
  is us export: No
  Salvaging a threatened limb is the key therapeutic objective for patients with critical limb
        ischemia, and the achievement of limb salvage is an independent predictor of patient
        morbidity and mortality. Despite successful primary endovascular or surgical intervention,
        the corresponding symptoms of rest pain and/or non-healing ulceration in some patients may
        continue, and amputation in these patients is unavoidable. We hypothesize that the functional
        integrity of the peripheral vascular microcirculation may be impaired in these patients.
        However, there are currently no techniques that allow direct quantification and visualization
        of the microcirculation due to the micro-vessel invisibility under angiography.
  
        In the coronary circulation, coronary flow reserve (CFR) indicates the capacity for maximal
        hyperemic blood flow and reveals impaired coronary microvascular function (Mcginn 1990,
        Nahser 1995). Studies have shown the clinical significance of measuring microvascular
        resistance to predict myocardial salvage after myocardial infarction (Payne, 2012). We are
        interested in whether this concept of coronary flow reserve can be applied peripherally to
        patients with critical limb ischemia in order to determine whether measuring peripheral
        vascular flow reserve can determine the integrity of the microcirculation to predict limb
        salvage after endovascular intervention.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Diagnostic
  masking: None (Open Label)
  measure: Efficacy of the peripheral flow reserve
  time frame: 6 months post-endovascular intervention
  description: To assess whether peripheral flow reserve can predict the success rate of limb salvage in critical limb ischemia patients after endovascular intervention. Assessed by any amputation (major or minor) at 6 months post-endovascular intervention.
  measure: Symptom resolution - Ulcer healing (1m)
  time frame: 1 month post-endovascular intervention
  description: Ulcer healing: changes in the number and extent of leg ulcers compared to baseline.
  measure: Symptom resolution - Ulcer healing (6m)
  time frame: 6 months post-endovascular intervention
  description: Ulcer healing: changes in the number and extent of leg ulcers compared to baseline.
  measure: Symptom resolution - Pain (1m)
  time frame: 1 month post-endovascular intervention
  description: Resolution of rest pain and alteration in visual analogue pain compared to baseline.
  measure: Symptom resolution - Pain (6m)
  time frame: 6 months post-endovascular intervention
  description: Resolution of rest pain and alteration in visual analogue pain compared to baseline.
  measure: Ankle-brachial index (ABI) (1m)
  time frame: 1 month post-endovascular intervention
  description: Improvement in Ankle-brachial index (ABI) compared to baseline.
  measure: Ankle-brachial index (ABI) (6m)
  time frame: 6 months post-endovascular intervention
  description: Improvement in Ankle-brachial index (ABI) compared to baseline.
  measure: Toe-brachial index (TBI) (1m)
  time frame: 1 month post-endovascular intervention
  description: Improvement in Toe-brachial index (TBI) compared to baseline.
  measure: Toe-brachial index (TBI) (6m)
  time frame: 6 months post-endovascular intervention
  description: Improvement in Toe-brachial index (TBI) compared to baseline.
  measure: Rutherford classification (1m)
  time frame: 1 month post-endovascular intervention
  description: Use of The Rutherford classification to assess peripheral artery disease compared to baseline. A 7 category scale is being used with 0 being Asymptomatic and 6 being Ulceration or gangrene.
  measure: Rutherford classification (6m)
  time frame: 6 months post-endovascular intervention
  description: Use of The Rutherford classification to assess peripheral artery disease compared to baseline. A 7 category scale is being used with 0 being Asymptomatic and 6 being Ulceration or gangrene.
  measure: Transcutaneous oxygen partial pressure (TcPO2) (1m)
  time frame: 1 month post-endovascular intervention
  description: Transcutaneous partial pressure of oxygen (TcPO2) will be measured representing the amount of oxygen diffusing outward across the skin (used as a surrogate for arterial perfusion).
  measure: Transcutaneous oxygen partial pressure (TcPO2) (6m)
  time frame: 6 months post-endovascular intervention
  description: Transcutaneous partial pressure of oxygen (TcPO2) will be measured representing the amount of oxygen diffusing outward across the skin (used as a surrogate for arterial perfusion).
  measure: Target lesion revascularization (1m)
  time frame: At 1 month post-endovascular intervention
  description: Need for revascularization (yes/no)
  measure: Target lesion revascularization (6m)
  time frame: At 6 month post-endovascular intervention
  description: Need for revascularization (yes/no)
  arm group label: Peripheral vascular flow reserve measurement
  arm group type: Experimental
  description: Post-procedure peripheral vascular flow reserve by thermodilution will be measured by the pressure wire.
  intervention type: Diagnostic Test
  intervention name: Peripheral vascular flow reserve measurement
  description: Peripheral arterial (below knee popliteal and above the level of ankle distal tibial) thermodilution curves will be obtained. One of the distal tibial arteries (anterior tibial, posterior tibial or peroneal artery, whichever reaches the most distal part of the foot in the run off) will be picked for measurements. At room temperature, 3 ml of saline will be injected brisk manually to determine the peak arterial flow, presented as mean transit time (Tmn). Resting Tmn will be performed and averaged by triplicate measurements at baseline. Then maximal hyperemia will be induced by intra-arterial injection of 30 mg papaverine through the guiding catheter, then 3 ml of saline will be injected to get hyperemic Tmn averaged by triplicate measurements. The guidewire will be kept in a fixed position during the series of measurements. Peripheral vascular flow reserve was calculated as resting Tmn divided by hyperemic Tmn (Fukunaga 2015).
  arm group label: Peripheral vascular flow reserve measurement
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: David O'Connor, MD
  role: Principal Investigator
  affiliation: Hackensack Meridian Health
  last name: Patricia Arakelian, RN
  phone: 5519962000
  phone ext: 5722
  email: patricia.arakelian@hmhn.org
  last name: Stephanie Lynes, RN
  phone: 5519962000
  phone ext: 5595
  email: Stephanie.Lynes@hmhn.org
  citation: McGinn, A.L., White, C.W. and Wilson, R.F., 1990. Interstudy variability of coronary flow reserve. Influence of heart rate, arterial pressure, and ventricular preload. Circulation, 81(4), pp.1319-1330. Nahser Jr, P.J., Brown, R.E., Oskarsson, H., Winniford, M.D. and Rossen, J.D., 1995. Maximal coronary flow reserve and metabolic coronary vasodilation in patients with diabetes mellitus. Circulation, 91(3), pp.635-640. Payne, A.R., Berry, C., Doolin, O., McEntegart, M., Petrie, M.C., Lindsay, M.M., Hood, S., Carrick, D., Tzemos, N., Weale, P. and McComb, C., 2012. Microvascular resistance predicts myocardial salvage and infarct characteristics in ST-elevation myocardial infarction. Journal of the American Heart Association, 1(4), p.e002246. Camici, P.G., d'Amati, G. and Rimoldi, O., 2015. Coronary microvascular dysfunction: mechanisms and functional assessment. Nature Reviews Cardiology, 12(1), p.48.
  citation: Fukunaga M, Fujii K, Kawasaki D, Nishimura M, Horimatsu T, Saita T, Miki K, Tamaru H, Imanaka T, Naito Y, Masuyama T. Vascular flow reserve immediately after infrapopliteal intervention as a predictor of wound healing in patients with foot tissue loss. Circ Cardiovasc Interv. 2015 Jun;8(6):e002412. doi: 10.1161/CIRCINTERVENTIONS.115.002412.
  PMID: 26019143
  citation: Crea, F., Lanza, G.A. and Camici, P.G., 2014. Mechanisms of coronary microvascular dysfunction. In Coronary Microvascular Dysfunction (pp. 31-47). Springer, Milano.
  citation: Pijls NH, De Bruyne B, Smith L, Aarnoudse W, Barbato E, Bartunek J, Bech GJ, Van De Vosse F. Coronary thermodilution to assess flow reserve: validation in humans. Circulation. 2002 May 28;105(21):2482-6. doi: 10.1161/01.cir.0000017199.09457.3d.
  PMID: 12034653
  citation: Kern MJ. Coronary physiology revisited : practical insights from the cardiac catheterization laboratory. Circulation. 2000 Mar 21;101(11):1344-51. doi: 10.1161/01.cir.101.11.1344.
  PMID: 10725297
  responsible party type: Sponsor
  mesh term: Peripheral Arterial Disease
  mesh term: Peripheral Vascular Diseases
  sharing ipd: No