Optimization of Treatment in Patients With Severe Peripheral Ischemia (Fontaine Stage IIb) (2bPILOT)

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

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

Study Overview

• Status: Completed
• Conditions: Peripheral Arterial Disease
• Intervention / Treatment: Drug: iloprost; Drug: Standard Treatment (aspirin.....),

Detailed Description

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".

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Bari, Italy, 70124
    • Internal Medicine, Hospital "Policlinico"
  • Catania, Italy, 95100
    • Angiology, Hospital "Ferrarotto - Alessi"
  • Catanzaro, Italy, 88100
    • Internal Medicine, Hospital "Pugliese - Ciaccio"
  • Fermo, Italy, 63900
    • Internal Medicine, Hospital of Fermo
  • Genoa, Italy, 16128
    • Vascular Surgery, Hospital "Galliera"
  • Legnano, Italy, 20025
    • Internal Medicine, Hospital Civile
  • Matera, Italy, 75100
    • Internal Medicine, "Madonna delle Grazie" Hospital
  • Naples, Italy, 80123
    • Internal Medicine, Hospital "Fatebenefratelli"
  • Naples, Italy, 80144
    • Surgery Dept., Hospital " San Giovanni Bosco"
  • Reggio Calabria, Italy, 89100
    • Internal Medicine, Hospital "Bianchi Melacrino Morelli"
  • Rome, Italy, 00155
    • Internal Medicine, Hospital Policlinico Campus Biomedico
  • Varese, Italy, 21100
    • Internal Medicine, Hospital "Fondazione Circolo Macchi"
  • Vibo Valentia, Italy, 89900
    • Internal Medicine, Hospital "Jazzolino"
  • Salerno
    • Mercato San Severino, Salerno, Italy, 84085
      • Angiology, Hospital "G. Fucito"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: age > 18 years; pain-free walking distance (PFWD) <100 meters on two occasions 10 days apart, with <25% difference between each other; ankle blood pressure (BP) <70 mmHg; big toe BP < 30 mmHg (in case of diabetic patient).

Exclusion Criteria: pain at rest, trophic ulcers or gangrene (critical limb ischemia), if they were unable to cooperate, or one of the following conditions (contraindications or precautions for use of iloprost) was present: myocardial infarction or stroke in the previous 6 months; congestive heart failure NYHA class >II; unstable angina; uncontrolled severe arterial hypertension (systolic BP >180 mmHg or diastolic BP >110 mmHg) or hypotension (systolic BP <90 mmHg); hyperkinetic ventricular arrhythmia; acute pulmonary edema or pulmonary congestion; bleeding diathesis; platelet count <80,000 or > 500,000/mm3; renal failure requiring dialysis; liver cirrhosis; pregnancy or breast feeding; history of allergy, hypersensitivity or intolerance to iloprost or other prostanoids.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: iloprost + standard treat.(aspirin); 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	Drug: iloprost; 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; Other Names: ENDOPROST*0,05MG/0,5ML 1F; Drug: Standard Treatment (aspirin.....),; 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; Other Names: aspirin, antiplatelet, statins,hemorheological/vasodilators
Active Comparator: Standard Treatment (aspirin....); 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	Drug: Standard Treatment (aspirin.....),; 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; Other Names: aspirin, antiplatelet, statins,hemorheological/vasodilators
Experimental: Vascular surgery patients + iloprost; 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	Drug: iloprost; 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; Other Names: ENDOPROST*0,05MG/0,5ML 1F; Drug: Standard Treatment (aspirin.....),; 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; Other Names: aspirin, antiplatelet, statins,hemorheological/vasodilators
Active Comparator: Vasc. Surg.+ standard treat. (aspirin..); 2A - patients suitable to vascular surgical or endovascular therapy + standard treatment (aspirin...)	Drug: Standard Treatment (aspirin.....),; 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; Other Names: aspirin, antiplatelet, statins,hemorheological/vasodilators

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of PFWD(pain-free walking distance)in patients with 2b stage PAD	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)	13 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessing changes in endurance	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)	13 months
The possible occurrence of major complications	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	13 months
Quality of life	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	13 months

Collaborators and Investigators

• Sponsor: Fadoi Foundation, Italy
• Investigators: Study Director: Gualberto Gussoni, MD, PhD, FADOI Foundation

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: October 22, 2012
• First Submitted That Met QC Criteria: October 29, 2012
• First Posted (Estimate): October 31, 2012

Study Record Updates

• Last Update Posted (Estimate): October 31, 2012
• Last Update Submitted That Met QC Criteria: October 29, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: PAD; iloprost; walking distance; cardiovascular events
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Ischemia; Peripheral Arterial Disease; Peripheral Vascular Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin; Iloprost
• Other Study ID Numbers: Eudract Number: 2006-001660-23