<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/NCT01718288</url>
  </required_header>
  <id_info>
    <org_study_id>Eudract Number: 2006-001660-23</org_study_id>
    <nct_id>NCT01718288</nct_id>
  </id_info>
  <brief_title>Optimization of Treatment in Patients With Severe Peripheral Ischemia (Fontaine Stage IIb)</brief_title>
  <acronym>2bPILOT</acronym>
  <official_title>Optimization of Treatment in Patients With Severe Peripheral Ischemia (Fontaine Stage IIb), Unsuitable or Suitable to Surgical Revascularization / Endovascular With Reference to the Change of Pain-free Walking Distance and Other Endpoints</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fadoi Foundation, Italy</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fadoi Foundation, Italy</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Evaluate the possibility of optimization of therapy with prostanoids (iloprost), in patients&#xD;
      with Fontaine's stage IIb severe chronic ischemia, both in patients eligible for surgery both&#xD;
      in patients for which it is only possible medical therapy&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The management of patients with peripheral arterial disease (PAD) stage IIb and pain-free&#xD;
      walking distance (PFWD) less than 100 meters is a major clinical problem, in view of the&#xD;
      significant cooling of the quality of life and evolution often severe that characterizes the&#xD;
      clinical course of these patients. Revascularization Surgery is the treatment of choice, but&#xD;
      about half of patients with severe PAD IIb is not eligible for surgery or endovascular&#xD;
      treatment. The usefulness of use of vasodilators or hemorheological is controversial, and&#xD;
      medical treatment of these patients is therefore heterogeneous understanding the various&#xD;
      pharmacologic options (for the correction of risk factors, prevention of cardiovascular&#xD;
      events, improvement of claudication), and rehabilitative programs. Iloprost, a synthetic&#xD;
      analogue of prostacyclin, is effective in the treatment of patients with chronic critical&#xD;
      ischemia, and its pharmacological profile (effective vasodilator, anti-platelet, and&#xD;
      leukocyte activation) is particularly suitable to modulate multiple components pathogenesis&#xD;
      of peripheral arterial disease. Specifically, in the treatment of patients with PAD IIb&#xD;
      severe, the current state is available only a retrospective study that compared the use of&#xD;
      iloprost with that of vasodilators. Aim of the study FADOI-2bPILOT is to evaluate&#xD;
      prospectively and for an observation period of 13 months, if you can get a benefit on the&#xD;
      pain-free walking distance and on clinical outcome from &quot;anticipated&quot; and additional use of&#xD;
      iloprost, in patients with severe IIb stage PAD treated according to current &quot;best medical&#xD;
      practice&quot;.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2006</start_date>
  <completion_date type="Actual">April 2012</completion_date>
  <primary_completion_date type="Actual">March 2011</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Measure of PFWD(pain-free walking distance)in patients with 2b stage PAD</measure>
    <time_frame>13 months</time_frame>
    <description>Aim of this multicenter, randomized, controlled study was prospectively evaluate the effects of iloprost, added to standard therapy, in patients with 2b stage PAD and PFWD (pain-free walking distance) less than 100 metres, eligible and non-eligible for surgical revascularization. A treadmill test 3-6-9-12 months (before iloprost cycle for patients group 1B and 2B). A final evaluation 13 months (for one month to the conclusion of the 12 months treatment of iloprost for patients group 1B and 2B, and after 13 months from enrolling for patients in the study group 1A and 2A)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assessing changes in endurance</measure>
    <time_frame>13 months</time_frame>
    <description>A clinical evaluation 3-6-9-12 months (before iloprost cycle for patients group 1B and 2B). A final evaluation 13 months (for one month to the conclusion of the 12 months treatment of iloprost for patients group 1B and 2B, and after 13 months from enrolling for patients in the study group 1A and 2A)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The possible occurrence of major complications</measure>
    <time_frame>13 months</time_frame>
    <description>The study reported the number of events during all the study (13 months). The major complication were: Ischemic cardiopathy, critical limb ischemia, cerebrovascular event, critical limb ischemia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life</measure>
    <time_frame>13 months</time_frame>
    <description>For the Quality of life, the study used a specific questionnaire administrated to all patients enrolled in the study (13 months of observation): IQOLA (International Quality of Life Assessment),SF-36 Italian Version 1.6</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">150</enrollment>
  <condition>Peripheral Arterial Disease</condition>
  <arm_group>
    <arm_group_label>iloprost + standard treat.(aspirin)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1B - patients unsuitable to surgical or endovascular vascular therapy: treatment with iloprost intravenous infusions for 10 days every 3 months, in addition to conventional treatment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard Treatment (aspirin....)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>1A - patients unsuitable to surgical or endovascular vascular therapy: conventional treatment&#xD;
Conventional Treatments:correction of concomitant risk factors, physical exercise, antiplatelet, standard heparin / low molecular weight heparin, hemorheological / vasodilators such as pentoxifylline / buflomedil, propionyl-L-carnitine, Defibrotide) but not prostanoids</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vascular surgery patients + iloprost</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2B - patients suitable to vascular surgical or endovascular therapy: treatment with intravenous infusions iloprost for 10 days every 3 months, in addition to conventional treatment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vasc. Surg.+ standard treat. (aspirin..)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>2A - patients suitable to vascular surgical or endovascular therapy + standard treatment (aspirin...)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>iloprost</intervention_name>
    <description>The study, consists of two substudies, which deal with patients susceptible to medical therapy alone (substudy 1) or treated with classical surgical therapy (substudy 2).&#xD;
For each substudy, pts will be divided into two groups, one that will receive conventional treatments but not prostanoids, other conventional treatments with addition of iloprost.&#xD;
The 4 groups:&#xD;
1A. Pts unsuitable to surgical or endovascular vascular therapy: conventional treatment&#xD;
B. Pts unsuitable to surgical or endovascular vascular therapy: treatment with iloprost plus conventional treatment&#xD;
A. Pts suitable to vascular surgical or endovascular therapy: conventional treatment&#xD;
2B. Pts suitable to vascular surgical or endovascular therapy: treatment with iloprost plus conventional treatment</description>
    <arm_group_label>Vascular surgery patients + iloprost</arm_group_label>
    <arm_group_label>iloprost + standard treat.(aspirin)</arm_group_label>
    <other_name>ENDOPROST*0,05MG/0,5ML 1F</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard Treatment (aspirin.....),</intervention_name>
    <description>The standard treatment, as has already been explained in the submission is the best treatment that the guidelines suggest for that specific type of patient with those complications and with stage 2b severe PAD.&#xD;
correction of concomitant risk factors, physical exercise, antiplatelet, standard heparin /low molecular weight heparin, hemorheological/vasodilators such as pentoxifylline/buflomedil, propionyl-L-carnitine, Defibrotide) but not prostanoids</description>
    <arm_group_label>Standard Treatment (aspirin....)</arm_group_label>
    <arm_group_label>Vasc. Surg.+ standard treat. (aspirin..)</arm_group_label>
    <arm_group_label>Vascular surgery patients + iloprost</arm_group_label>
    <arm_group_label>iloprost + standard treat.(aspirin)</arm_group_label>
    <other_name>aspirin, antiplatelet, statins,hemorheological/vasodilators</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria: age &gt; 18 years; pain-free walking distance (PFWD) &lt;100 meters on two&#xD;
        occasions 10 days apart, with &lt;25% difference between each other; ankle blood pressure (BP)&#xD;
        &lt;70 mmHg; big toe BP &lt; 30 mmHg (in case of diabetic patient).&#xD;
&#xD;
        Exclusion Criteria: pain at rest, trophic ulcers or gangrene (critical limb ischemia), if&#xD;
        they were unable to cooperate, or one of the following conditions (contraindications or&#xD;
        precautions for use of iloprost) was present: myocardial infarction or stroke in the&#xD;
        previous 6 months; congestive heart failure NYHA class &gt;II; unstable angina; uncontrolled&#xD;
        severe arterial hypertension (systolic BP &gt;180 mmHg or diastolic BP &gt;110 mmHg) or&#xD;
        hypotension (systolic BP &lt;90 mmHg); hyperkinetic ventricular arrhythmia; acute pulmonary&#xD;
        edema or pulmonary congestion; bleeding diathesis; platelet count &lt;80,000 or &gt; 500,000/mm3;&#xD;
        renal failure requiring dialysis; liver cirrhosis; pregnancy or breast feeding; history of&#xD;
        allergy, hypersensitivity or intolerance to iloprost or other prostanoids.&#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>Gualberto Gussoni, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Fadoi Foundation</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Angiology, Hospital &quot;G. Fucito&quot;</name>
      <address>
        <city>Mercato San Severino</city>
        <state>Salerno</state>
        <zip>84085</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Internal Medicine, Hospital &quot;Policlinico&quot;</name>
      <address>
        <city>Bari</city>
        <zip>70124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Angiology, Hospital &quot;Ferrarotto - Alessi&quot;</name>
      <address>
        <city>Catania</city>
        <zip>95100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Internal Medicine, Hospital &quot;Pugliese - Ciaccio&quot;</name>
      <address>
        <city>Catanzaro</city>
        <zip>88100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Internal Medicine, Hospital of Fermo</name>
      <address>
        <city>Fermo</city>
        <zip>63900</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vascular Surgery, Hospital &quot;Galliera&quot;</name>
      <address>
        <city>Genoa</city>
        <zip>16128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Internal Medicine, Hospital Civile</name>
      <address>
        <city>Legnano</city>
        <zip>20025</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Internal Medicine, &quot;Madonna delle Grazie&quot; Hospital</name>
      <address>
        <city>Matera</city>
        <zip>75100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Internal Medicine, Hospital &quot;Fatebenefratelli&quot;</name>
      <address>
        <city>Naples</city>
        <zip>80123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Surgery Dept., Hospital &quot; San Giovanni Bosco&quot;</name>
      <address>
        <city>Naples</city>
        <zip>80144</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Internal Medicine, Hospital &quot;Bianchi Melacrino Morelli&quot;</name>
      <address>
        <city>Reggio Calabria</city>
        <zip>89100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Internal Medicine, Hospital Policlinico Campus Biomedico</name>
      <address>
        <city>Rome</city>
        <zip>00155</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Internal Medicine, Hospital &quot;Fondazione Circolo Macchi&quot;</name>
      <address>
        <city>Varese</city>
        <zip>21100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Internal Medicine, Hospital &quot;Jazzolino&quot;</name>
      <address>
        <city>Vibo Valentia</city>
        <zip>89900</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>October 2012</verification_date>
  <study_first_submitted>October 22, 2012</study_first_submitted>
  <study_first_submitted_qc>October 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 31, 2012</study_first_posted>
  <last_update_submitted>October 29, 2012</last_update_submitted>
  <last_update_submitted_qc>October 29, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 31, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PAD; iloprost; walking distance; cardiovascular events</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>
    <mesh_term>Ischemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
    <mesh_term>Iloprost</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>December 28, 2018</submitted>
    <returned>January 22, 2019</returned>
    <submitted>May 17, 2019</submitted>
    <returned>June 10, 2019</returned>
    <submitted>January 31, 2020</submitted>
    <returned>February 11, 2020</returned>
    <submitted>May 5, 2021</submitted>
    <returned>May 27, 2021</returned>
    <submitted>September 24, 2021</submitted>
    <returned>October 21, 2021</returned>
  </pending_results>
  <!-- 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/NCT01718288
org study id: Eudract Number: 2006-001660-23
nct id: NCT01718288
lead sponsor: 
has dmc: Yes
Evaluate the possibility of optimization of therapy with prostanoids (iloprost), in patients
      with Fontaine's stage IIb severe chronic ischemia, both in patients eligible for surgery both
      in patients for which it is only possible medical therapy
The management of patients with peripheral arterial disease (PAD) stage IIb and pain-free
      walking distance (PFWD) less than 100 meters is a major clinical problem, in view of the
      significant cooling of the quality of life and evolution often severe that characterizes the
      clinical course of these patients. Revascularization Surgery is the treatment of choice, but
      about half of patients with severe PAD IIb is not eligible for surgery or endovascular
      treatment. The usefulness of use of vasodilators or hemorheological is controversial, and
      medical treatment of these patients is therefore heterogeneous understanding the various
      pharmacologic options (for the correction of risk factors, prevention of cardiovascular
      events, improvement of claudication), and rehabilitative programs. Iloprost, a synthetic
      analogue of prostacyclin, is effective in the treatment of patients with chronic critical
      ischemia, and its pharmacological profile (effective vasodilator, anti-platelet, and
      leukocyte activation) is particularly suitable to modulate multiple components pathogenesis
      of peripheral arterial disease. Specifically, in the treatment of patients with PAD IIb
      severe, the current state is available only a retrospective study that compared the use of
      iloprost with that of vasodilators. Aim of the study FADOI-2bPILOT is to evaluate
      prospectively and for an observation period of 13 months, if you can get a benefit on the
      pain-free walking distance and on clinical outcome from "anticipated" and additional use of
      iloprost, in patients with severe IIb stage PAD treated according to current "best medical
      practice".
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Measure of PFWD(pain-free walking distance)in patients with 2b stage PAD
time frame: 13 months
description: Aim of this multicenter, randomized, controlled study was prospectively evaluate the effects of iloprost, added to standard therapy, in patients with 2b stage PAD and PFWD (pain-free walking distance) less than 100 metres, eligible and non-eligible for surgical revascularization. A treadmill test 3-6-9-12 months (before iloprost cycle for patients group 1B and 2B). A final evaluation 13 months (for one month to the conclusion of the 12 months treatment of iloprost for patients group 1B and 2B, and after 13 months from enrolling for patients in the study group 1A and 2A)
measure: Assessing changes in endurance
time frame: 13 months
description: A clinical evaluation 3-6-9-12 months (before iloprost cycle for patients group 1B and 2B). A final evaluation 13 months (for one month to the conclusion of the 12 months treatment of iloprost for patients group 1B and 2B, and after 13 months from enrolling for patients in the study group 1A and 2A)
measure: The possible occurrence of major complications
time frame: 13 months
description: The study reported the number of events during all the study (13 months). The major complication were: Ischemic cardiopathy, critical limb ischemia, cerebrovascular event, critical limb ischemia
measure: Quality of life
time frame: 13 months
description: For the Quality of life, the study used a specific questionnaire administrated to all patients enrolled in the study (13 months of observation): IQOLA (International Quality of Life Assessment),SF-36 Italian Version 1.6
arm group label: iloprost + standard treat.(aspirin)
arm group type: Experimental
description: 1B - patients unsuitable to surgical or endovascular vascular therapy: treatment with iloprost intravenous infusions for 10 days every 3 months, in addition to conventional treatment
arm group label: Standard Treatment (aspirin....)
arm group type: Active Comparator
description: 1A - patients unsuitable to surgical or endovascular vascular therapy: conventional treatment
Conventional Treatments:correction of concomitant risk factors, physical exercise, antiplatelet, standard heparin / low molecular weight heparin, hemorheological / vasodilators such as pentoxifylline / buflomedil, propionyl-L-carnitine, Defibrotide) but not prostanoids
arm group label: Vascular surgery patients + iloprost
arm group type: Experimental
description: 2B - patients suitable to vascular surgical or endovascular therapy: treatment with intravenous infusions iloprost for 10 days every 3 months, in addition to conventional treatment
arm group label: Vasc. Surg.+ standard treat. (aspirin..)
arm group type: Active Comparator
description: 2A - patients suitable to vascular surgical or endovascular therapy + standard treatment (aspirin...)
intervention type: Drug
intervention name: iloprost
description: The study, consists of two substudies, which deal with patients susceptible to medical therapy alone (substudy 1) or treated with classical surgical therapy (substudy 2).
For each substudy, pts will be divided into two groups, one that will receive conventional treatments but not prostanoids, other conventional treatments with addition of iloprost.
The 4 groups:
1A. Pts unsuitable to surgical or endovascular vascular therapy: conventional treatment
B. Pts unsuitable to surgical or endovascular vascular therapy: treatment with iloprost plus conventional treatment
A. Pts suitable to vascular surgical or endovascular therapy: conventional treatment
2B. Pts suitable to vascular surgical or endovascular therapy: treatment with iloprost plus conventional treatment
arm group label: Vascular surgery patients + iloprost
arm group label: iloprost + standard treat.(aspirin)
other name: ENDOPROST*0,05MG/0,5ML 1F
intervention type: Drug
intervention name: Standard Treatment (aspirin.....),
description: The standard treatment, as has already been explained in the submission is the best treatment that the guidelines suggest for that specific type of patient with those complications and with stage 2b severe PAD.
correction of concomitant risk factors, physical exercise, antiplatelet, standard heparin /low molecular weight heparin, hemorheological/vasodilators such as pentoxifylline/buflomedil, propionyl-L-carnitine, Defibrotide) but not prostanoids
arm group label: Standard Treatment (aspirin....)
arm group label: Vasc. Surg.+ standard treat. (aspirin..)
arm group label: Vascular surgery patients + iloprost
arm group label: iloprost + standard treat.(aspirin)
other name: aspirin, antiplatelet, statins,hemorheological/vasodilators
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gualberto Gussoni, MD, PhD
role: Study Director
affiliation: Fadoi Foundation
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Italy
responsible party type: Sponsor
mesh term: Peripheral Arterial Disease
mesh term: Peripheral Vascular Diseases
mesh term: Ischemia
mesh term: Aspirin
mesh term: Iloprost
submitted: December 28, 2018
returned: January 22, 2019
submitted: May 17, 2019
returned: June 10, 2019
submitted: January 31, 2020
returned: February 11, 2020
submitted: May 5, 2021
returned: May 27, 2021
submitted: September 24, 2021
returned: October 21, 2021