Peripheral Extreme Revascularization in "No-option" Patiens With Chronic Limb Threatening Ischemia (PiPER)

"Arterial-Venous Reversal Flow in "No-option" Chronic Limb-threating Ischemia (CLTI) Patients"

The objective of the study is to evaluate early safety and effectiveness of the percutaneous deep foot venous arterialization performed in clinical practice, in an unselected population of patients with "no-option" CLTI.

Study Overview

• Status: Recruiting
• Conditions: Diabetic Foot; Peripheral Arterial Disease; Critical Limb-Threatening Ischemia

Detailed Description

Critical lower Limb Threatening Ischemia is the most advanced stage of lower limb arterial disease and is associated with a high risk of mortality and major amputation.Literature data indicate that about 5-10% of patients with peripheral arterial disease have a risk of developing CLTI, therefore the most advanced stage of arterial disease of the lower limbs, within 5 years and have a mortality of 20% at 6 months after diagnosis of CLTI.Despite the continuous improvement of the techniques and materials used in the revascularization of these patients, the data of the Literature show that in about 10-15% of these patients revascularization is impossible or ineffective. This condition is defined as: "no-option" CLTI.Therefore, for patients with "no-option" CLTI an alternative treatment for limb rescue may be considered the use of arterialization of the venous plexus of the foot; that is, to use to bring the arterial flow to the foot a healthy conduit, such as the vein, instead of the diseased artery and no longer usable.

The present study is designed as a multicentre, prospective, single-arm, observational study.

All eligible subjects for undergoing PiPER procedure at sites participating in the study will be considered for enrolment and will be asked to give consent prior to participating.

Subjects will be considered enrolled in the study at the time written informed consent is given to the use of their personal data. Once patients are enrolled, their demographics, medical history, disease-relevant conditions, treatment details and outcomes will be collected for up to 24 months from the procedure.

The study will collect information about the medical care patients receive during their planned procedure. No additional testing or procedures will be done.

The revascularization procedure will be performed as per the current clinical practice.

After discharge all patients will attend clinic visits at 30 days (±7 days), 6 months (±14 days),12 months (±30 days), 24 months (±30 days).

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Bruno Migliara, MD; Email: bruno.migliara@gmail.com
• Study Contact Backup: Name: Gabriele Morselli, PharmD; Phone Number: +39 3499105666; Email: g.morselli@endocorelab.org

Study Locations

• Italy
  • Ancona
    • Ancona, Ancona, Italy, 60129
      • Recruiting
      • Irccs Inrca
      • Contact: Enrico Paci, MD
  • Italy
    • Belluno, Italy, Italy, 32100
      • Recruiting
      • Ospedale San Martino
      • Principal Investigator: Luca Ferretto, MD
      • Contact: Sandro Irsara, MD
    • Cesena, Italy, Italy, 47521
      • Recruiting
      • Ospedale Bufalini
      • Contact: Gabriele Testi, MD
      • Principal Investigator: Gabriele Testi, MD
    • Conegliano, Italy, Italy, 31015
      • Withdrawn
      • Ospedale di Conegliano - USLL2
    • Naples, Italy, Italy, 80131
      • Recruiting
      • Ospedale Cardarelli
      • Contact: Gianluca Cangiano, MD
      • Principal Investigator: Gianluca Cangiano, MD
    • Reggio Emilia, Italy, Italy, 42122
      • Withdrawn
      • Arcispedale Santa Maria Nuova
    • Trento, Italy, Italy, 38123
      • Recruiting
      • Ospedale Santa Chiara
      • Contact: Stefano Bonvini, MD
      • Principal Investigator: Stenano Bonvini, MD
  • Perugia
    • Perugia, Perugia, Italy, 06156
      • Not yet recruiting
      • Azienda Ospedaliera S. Maria Della Misericordia
      • Contact: Massimo Lenti, MD
  • Veneto
    • Peschiera del Garda, Veneto, Italy, 37019
      • Recruiting
      • Ospedale Pederzoli
      • Contact: Bruno Migliara, MD; Email: bruno.migliara@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Subjects presenting the most advanced stage of lower limb arterial disease, defined as patients with CLTI and no indication for revascularization.

Description

Inclusion Criteria:

• Age ≥18 years
• Patient has signed an approved informed consent form
• All patients, with non-revascularizable critical lower limb ischemia defined on the basis of 2 previous unsuccessful Percutaneous Transluminal Angioplasty (PTA) attempts or on severe Medial Artery Calcification (MAC)/Small Artery Disease (SAD) stage.
• Patient with Critical Limb Ischaemia, Rutherford category, 5 (minor tissue loss) or 6 (major tissue loss) with active trophic lesions
• Ejection Fraction > 30%

Exclusion Criteria:

• Subject no able to perform the follow up or other factors making clinical follow-up difficult
• Patients with critical ischaemia of the lower limbs revascularizable by bypass or angioplasty, critical ischaemia characterised by rest pain (Rutherford class ≤ 4)
• Ejection Fraction < 30%

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Composite	Composite of amputation free survival, defined as the rate of limb salvage (freedom from major amputation) and survival (freedom from all causes of death) of the percutaneous deep foot venous arterialization procedure.	30 days, 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Procedural Success	Procedural success (defined as completion of the procedure by percutaneous route with achievement of arterial flow in the venous plexus of the foot at the end, as angiographically assessed);	Day 1
Primary Patency	Primary patency defined as no occlusion of the arterialized vein tract	30 days, 3 months, 6 months, 12 months and 24 months
Secondary Patency	Secondary patency defined as no secondary occlusion of the arterialised vein tract	30 days, 3 months, 6 months, 12 months and 24 months
A-V fistula flow rate	A-V fistula flow rate	30 days, 3 months, 6 months, 12 months and 24 months
Minor amputation rates	Minor amputation rates defined as a below the ankle amputation	30 days, 3 months, 6 months, 12 months and 24 months
Major amputation rates	Major amputation rates defined as an above the ankle amputation	30 days, 3 months, 6 months, 12 months and 24 months
Re-Treatment rate	Re-Treatment rate defined as need for reintervention	30 days, 3 months, 6 months, 12 months and 24 months
Wound Size	Wound Size defined as wound size reduction index	Baseline, 30 days, 3 months, 6 months, 12 months and 24 months
TpcO2	TpcO2 defined as TpcO2 value changes	Baseline, 30 days, 3 months, 6 months, 12 months and 24 months
WIFi class	WIFi class and stage changes	Baseline, 30 days, 3 months, 6 months, 12 months and 24 months
Freedom from all cause death	Freedom from all cause death	30 days, 3 months, 6 months, 12 months and 24 months
Freedom from procedure-related death	Freedom from procedure-related death	30 days, 3 months
Rutherford class	Rutherford class and stage changes	Baseline, 30 days, 3 months, 6 months, 12 months and 24 months

Collaborators and Investigators

• Sponsor: EndoCore Lab s.r.l.
• Investigators: Study Director: Gabriele Morselli, PharmD, EndocoCore Lab s.r.l.; Principal Investigator: Bruno Migliara, MD, Casa di cura Pederzoli; Study Chair: Marco Manzi, MD, Casa di Cura Abano Terme

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2020
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: February 19, 2024
• First Submitted That Met QC Criteria: February 19, 2024
• First Posted (Actual): February 26, 2024

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: PAD; CLTI; DVA
• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Diabetes Mellitus; Diabetic Angiopathies; Diabetes Complications; Skin Diseases; Skin Ulcer; Leg Ulcer; Diabetic Neuropathies; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Vascular Diseases; Foot Ulcer; Skin and Connective Tissue Diseases; Diabetic Foot; Peripheral Arterial Disease
• Other Study ID Numbers: CLTI012023

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No