Chronic Limb-Threatening Ischemia Treated With Intravascular Lithotripsy Observational Study (CALCIO)

CALCIO is a multicentre, prospective, observational cohort study that will collect real world data on the use of intravascular Lithotripsy (IVL) with the Shockwave IVL system to disrupt calcified femoropopliteal and crural lesions in patients with chronic limb-threatening ischemia (CLTI). The primary objective of CALCIO is to understand the effectiveness of IVL in promoting wound healing and preventing amputation. The secondary objectives of CALCIO are to evaluate the immediate effectiveness of the treatment in restoring vessel patency as well as its safety and impact on patients' quality of life.

Study Overview

• Status: Recruiting
• Conditions: Chronic Limb-Threatening Ischemia
• Intervention / Treatment: Device: Shockwave Medical IVL System

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: Claire Poulet, PhD; Phone Number: +41 79 385 16 78; Email: calcio@cirse.org
• Study Contact Backup: Name: Dhwani S. Korde, PhD; Phone Number: +4367762942469; Email: calcio@cirse.org

Study Locations

• Austria
  • Eisenstadt, Austria, 7000
    • Recruiting
    • Krankenhaus der Barmherzigen Brüder
    • Principal Investigator: Martin Wehrschütz, Prim. Dr.
  • Graz, Austria, 8036
    • Recruiting
    • Medizinische Universitat Graz
    • Principal Investigator: Marianne Brodmann, Univ.-Prof. Dr.med.univ.
  • Linz, Austria, 4020
    • Recruiting
    • Krankenhaus Barmherzige Brüder Linz
    • Principal Investigator: Stefan Nöbauer, Dr. med.
  • Vienna, Austria, 1130
    • Recruiting
    • Klinik Hietzing
    • Principal Investigator: Fabian Hack, Dr
  • Vienna, Austria, 1210
    • Recruiting
    • Klinik Florisdorf
    • Principal Investigator: Thomas Rand, Univ. Prof. Prim. Dr.
• Canada
  • Montreal, Canada, H4J 1C5
    • Recruiting
    • Hôpital Sacré Coeur de Montréal
    • Principal Investigator: Ahmed Bentridi, Dr
• France
  • Dijon, France, 21000
    • Recruiting
    • CHU François Mitterrand
    • Principal Investigator: Romaric Loffroy, Dr
  • Paris, France, 75014
    • Recruiting
    • Institute Mutualiste Montsouris
    • Principal Investigator: Costantino Del Giudice, Dr
  • Strasbourg, France, 67000
    • Recruiting
    • Rhéna Clinique de Strasbourg
    • Principal Investigator: Gilles Goyault, Dr
• Germany
  • Cologne, Germany, 50937
    • Recruiting
    • Universitatsklinikum Koln
    • Principal Investigator: Robert P. Wawer Matos Reimer, Priv.-Doz. Dr.
  • Essen, Germany, 45147
    • Recruiting
    • Universitätsmedizin Essen
    • Principal Investigator: Christos Rammos, Dr
  • Hanover, Germany, 30989
    • Recruiting
    • KRH Klinikum Robert Koch Gehrden
    • Principal Investigator: Nikolaj Mokov, Dr. med.
    • Principal Investigator: Götz Voshage, Dr. med.
  • Heilbronn, Germany, 74078
    • Recruiting
    • SLK-Heilbronn
    • Principal Investigator: Gerd Grözinger, Prof. Dr. med.
  • Karlsruhe, Germany, 76133
    • Recruiting
    • Städtisches Klinikum
    • Principal Investigator: Peter Reimer, Prof. Dr.
  • Mülheim, Germany, 45468
    • Recruiting
    • Evangelisches Krankenhaus
    • Principal Investigator: Claus Nolte-Ernsting, Prof. Dr.
  • Neumünster, Germany, 24534
    • Recruiting
    • Friedrich Ebert Krankenhaus
    • Principal Investigator: Thomas Jahnke, Prof. Dr. med.
  • Rendsburg, Germany, 24768
    • Recruiting
    • Schön Klinik Rendsburg
    • Principal Investigator: Christian Wissgott, Priv.-Doz. Dr.
  • Siegen, Germany, 57072
    • Recruiting
    • St Marien-Krankenhaus
    • Principal Investigator: Christian Hohl, Priv.-Doz. Dr. med. Dipl.-Phys
  • Tübingen, Germany, 72076
    • Recruiting
    • Universitatsklinikum Tubingen
    • Principal Investigator: Jörg Schmehl, Dr. med.
• Hungary
  • Budapest, Hungary, 1085
    • Recruiting
    • Semmelweis University
    • Principal Investigator: Edit Dósa, Dr
• Spain
  • Alicante, Spain, 03010
    • Recruiting
    • Hospital General Universitario Dr. Balmis
    • Principal Investigator: Elisabeth Cruces Fuentes, Dr
  • Granollers, Spain, 08402
    • Recruiting
    • Hospital General de Granollers
    • Principal Investigator: Marc Sirvent, Dr
  • Pamplona, Spain, 31006
    • Recruiting
    • University of Navarra
    • Principal Investigator: Alberto Alonso Burgos, Dr
    • Principal Investigator: José Ignacio Leal, Dr
• Switzerland
  • Lugano, Switzerland, 6500
    • Recruiting
    • Ente Ospedaliero Cantonale
    • Principal Investigator: Maria Antonella Ruffino, Dr. med.
  • Winterthur, Switzerland, 8400
    • Recruiting
    • Kantonsspital Winterthur
    • Principal Investigator: Arash Najafi, PD Dr. med.
• United Kingdom
  • Bedford, United Kingdom, MK42 9DJ
    • Recruiting
    • Bedfordshire Hospitals NHS Foundation Trust
    • Principal Investigator: Ramita Dey, Dr
  • Frimley, United Kingdom, GU16 7UJ
    • Recruiting
    • Frimley Health NHS Foundation Trust
    • Principal Investigator: Muzzafer Chaudery, Dr
  • Hull, United Kingdom, HU3 2JZ
    • Recruiting
    • Hull University Teaching Hospitals NHS Trust
    • Principal Investigator: Raghuram Lakshminarayan, Dr
  • Leeds, United Kingdom, LS1 3EX
    • Recruiting
    • Leeds Teaching Hospitals NHS Trust
    • Principal Investigator: Omar Abdel-Hadi, Dr
  • Liverpool, United Kingdom, L7 8XP
    • Recruiting
    • Liverpool University Hospitals NHS Foundation Trust
    • Principal Investigator: Christopher Keegan, Dr
  • London, United Kingdom, W2 1NY
    • Recruiting
    • Imperial College Healthcare NHS Trust
    • Principal Investigator: Mohamad Hamady, Prof.
  • London, United Kingdom, NW3 2QG
    • Recruiting
    • Royal Free London NHS Foundation Trust
    • Principal Investigator: Conrad von Stempel, Dr
  • London, United Kingdom, NW1 2PG
    • Recruiting
    • University College London Hospitals Nhs Foundation Trust
    • Principal Investigator: Shanka Benaragama, Dr
  • London, United Kingdom, SW17 0QT
    • Recruiting
    • St George's University Hospitals NHS Foundation Trust
    • Principal Investigator: Leto Mailli, Dr
  • Manchester, United Kingdom, M13 9WL
    • Recruiting
    • Manchester University NHS Foundation Trust
    • Principal Investigator: Neville Nicholas, Dr
  • Newcastle, United Kingdom, NE1 4LP
    • Recruiting
    • Newcastle upon Tyne Hospitals NHS Foundation Trust
    • Principal Investigator: Colin Nice, Dr
  • Oxford, United Kingdom, OX3 9DU
    • Recruiting
    • Oxford University Hospitals NHS Foundation Trust
    • Principal Investigator: Raman Uberoi, Dr
  • Plymouth, United Kingdom, PL6 8DH
    • Recruiting
    • University Hospitals Plymouth NHS Trust
    • Principal Investigator: Paul Jenkins, Dr
  • Sheffield, United Kingdom, S10 2JF
    • Recruiting
    • Sheffield Teaching Hospitals NHS FT
    • Principal Investigator: Dinesh Manoharan, Dr

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

CLTI patients with calcified femoropopliteal or crural lesions visible on fluoroscopy and treated with Intravascular Lithotripsy.

Description

Inclusion Criteria:

• Patient with chronic limb-threatening ischemia (Rutherford Category ≥4)
• Femoropopliteal and/or crural calcified lesions visible on fluoroscopy;
• Treatment with IVl using the Shockwave Medical IVL System.

Exclusion Criteria:

• < 18 years old;
• Incapacity or refusal to give informed consent;
• Ongoing pregnancy;
• Endovascular procedure(s) on the treatment site within 4 weeks before the planned IVL treatment.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Full cohort; Intravascular lithotripsy of femoropopliteal and crural lesions as per standard of care	Device: Shockwave Medical IVL System; Comprehensive system consisting of generator, a connector cable and a single-use sterile catheter with integrated balloon for intravascular lithotripsy of peripheral artery calcification.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wound healing and freedom from amputation	Composite of wound healing defined as the healing status of the dominant ischemic wound of the target limb (complete, partial, unchanged, worsening) and freedom from amputation defined as the absence of any amputation of the treated limb: minor (digital, metatarsal), major below the knee or major above the knee (excluding any amputation planned before the IVL procedure).	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wound healing	Healing status of the dominant ischemic wound of the target limb (complete, partial, unchanged, worsening)	24 months
Freedom from amputation	Absence of any amputation of the treated limb: minor (digital, metatarsal), major below the knee or major above the knee (excluding any amputation planned before the IVL procedure).	24 months
Amputation-free survival	time between IVL treatment and amputation of the target limb, minor (digital, metatarsal), major below the knee or major above the knee (excluding any amputation planned before the IVL procedure)	through study completion, approximately 2 years
Change in Rutherford classification category	Seven classification categories, from 0 (asymptomatic) to 6 (Major tissue loss)	12 and 24 months
Change in foot ischemia	Change in ankle-brachial index or toe pressure, depending on which data is available	12 and 24 months
Change in WIfi score	Three-digit score for comprehensive assessment of wound, ischemia and foot infection	12 and 24 months
CD-TLR-free survival	time between IVL treatment and any endovascular re-intervention to the target lesion (± 10 mm)	through study completion, approximately 2 years
Primary patency rate	freedom from total occlusion without any endovascular or surgical re-intervention to the target lesion (± 10 mm)	12 and 24 months
Assisted primary patency rate	freedom from total occlusion following additional endovascular or surgical intervention(s) due to restenosis of the target lesion	12 and 24 months
Secondary patency rate	freedom from total occlusion following additional endovascular or surgical intervention(s) due to occlusion of the target lesion	12 and 24 months
Technical success of IVL	residual diameter stenosis ≤30% after IVL and before any potential adjunctive intervention	on the day of the procedure
Overall procedural success	residual stenosis ≤30% by the end of the complete procedure	on the day of the procedure
Patient-reported health-related quality-of-life	EuroQol questionnaire EQ-5D-5L	at 6, 12 and 24 months
Freedom from clinically-driven target lesion revascularization (CD-TLR)	freedom from any endovascular re-intervention to the target lesion (± 10 mm) or surgical bypass performed because of restenosis or occlusion of the target lesion.	12 and 24 months
Frequency and severity of procedural complications and other adverse events	Grading according to the classification system of the Cardiovascular and Interventional Radiological Society of Europe	Within 30 days after the procedure

Collaborators and Investigators

• Sponsor: Cardiovascular and Interventional Radiological Society of Europe
• Collaborators: Shockwave Medical, Inc.
• Investigators: Study Chair: Raman Uberoi, Dr, Oxford University Hospital NHS Foundation Trust, Oxford, United Kingdom; Study Chair: Christoph Binkert, Prof. Dr, Cantonal Hospital Winterthur, Winterthur, Switzerland; Study Chair: Peter Reimer, Prof. Dr, Municipal Clinic Karlsruhe, Karlsruhe, Germany

Publications and helpful links

General Publications

• Filippiadis DK, Binkert C, Pellerin O, Hoffmann RT, Krajina A, Pereira PL. Cirse Quality Assurance Document and Standards for Classification of Complications: The Cirse Classification System. Cardiovasc Intervent Radiol. 2017 Aug;40(8):1141-1146. doi: 10.1007/s00270-017-1703-4. Epub 2017 Jun 5.
• Uberoi R, Reimer P, Chun JY, Goyault G, Kashef E, Loffroy R, Rand T, Ruffino MA, von Stempel C, Lange T, Zeka B, Poulet C, Kaufmann N, Binkert C. Intravascular Lithotripsy for Patients with Chronic Limb-Threatening Ischemia: Study Protocol for CALCIO, a Prospective Multicenter Observational Investigation. Cardiovasc Intervent Radiol. 2026 Feb 17. doi: 10.1007/s00270-025-04335-w. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2024
• Primary Completion (Estimated): July 15, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: November 15, 2023
• First Submitted That Met QC Criteria: November 20, 2023
• First Posted (Actual): November 29, 2023

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: CLTI
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Chronic Disease; Disease Attributes; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Vascular Diseases; Ischemia; Peripheral Arterial Disease; Pathological Conditions, Signs and Symptoms; Chronic Limb-Threatening Ischemia
• Other Study ID Numbers: CALCIO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No