Major Adverse Limb Events in Patients With Femoro-popliteal and Below-the-knee Peripheral Arterial Disease Treated With Either Sirolimus-coated Balloon or Standard Uncoated Balloon Angioplasty

February 17, 2026 updated by: Nils Kucher
The SirPAD trial is an academic, investigator-initiated, single-center, randomized, non-inferiority, open-label clinical trial investigating whether the use of sirolimus-coated balloon catheters in patients with peripheral artery disease of the femoro-popliteal or below-the-knee segment is not inferior to that of uncoated balloon catheters for major clinical outcomes (unplanned major amputation, target limb re-vascularization) and may provide advantages concerning important secondary outcomes, which will be evaluated using a pre-specified hierarchical order as part of the primary analysis.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Peripheral artery disease (PAD) is a progressive atherosclerotic disease with symptoms ranging from intermittent claudication (IC) to critical limb ischemia (CLI). The majority of symptomatic PAD patients present with atherosclerotic lesions located in the femoro-popliteal arteries and endovascular therapy is the primary choice if the stenosis/occlusions involve <25 cm of the vessel. A minority of symptomatic PAD patients would present with infra-popliteal (distal or below-the-knee) lesions: in these patients, the endovascular treatment is challenging.

Drug-coated balloons (DCB) and drug-eluting stents (DES) were developed to prevent neo-intimal proliferation and restenosis after percutaneous transluminal angioplasty (PTA), an objective which had been achieved by the local application of either cytostatic (e.g. paclitaxel - a cytoskeletal disruptor) or immunosuppressive (e.g. sirolimus/everolimus - both mTOR inhibitors) substances on the vessel wall.

Over the past decade, a few randomized controlled trials (RCT) compared the efficacy and safety of drug-coated (mainly paclitaxel-coated) devices vs. that of uncoated ones, and demonstrated a significant reduction in restenosis rates, late lumen loss, and incidence of target lesion re-vascularization. However, the size of these trials was often too small to draw firm conclusions concerning major clinical outcomes. Moreover, substantial heterogeneity of the study populations and too restrictive eligibility criteria limited their external validity, leading to a difficult interpretation of the results of later meta-analyses. Indeed, these trials adopted as the primary outcome surrogate (and rather subjective) outcomes, such as vessel patency and target limb re-vascularization, which may be difficult to objectively adjudicate in the setting of an open-label trial, rather than ´hard´ objective clinical endpoints, such as major amputation or urgent revascularization due to critical limb ischemia.

Moreover, despite the short-term effects appeared promising based on imaging outcome, tthe results of a recent meta-analysis of 28 trials showed an increased two-year mortality in the group of patients treated with paclitaxel-coated balloons. Based on these results, and after analysis of follow-up data from the trials that led to the approval of these products, a Food and Drug Administration (FDA) panel concluded that, despite the short-term benefits with paclitaxel-based devices, safety concerns may exist for mid-term mortality risk.

Alternative drug candidates to paclitaxel-coated balloon catheters are the so-called limus-based analogs, which own cytostatic properties and are characterized by a wider therapeutic window. Recently, a novel balloon catheter has been CE-certified: it encapsulates sirolimus in phospholipid drug nanocarriers to improve adhesion properties of sirolimus and to provide better bioavailability. Similarly to paclitaxel-coated and uncoated devices, sirolimus-coated devices are currently approved for routine use in PAD and reimbursed in Switzerland.

The aim of the present trial is to compare the efficacy, as defined by a composite of clinically relevant non-subjective ´hard´ outcomes (major amputation and target lesion re-vascularization for critical limb ischemia), of sirolimus-coated vs. uncoated balloon angioplasty for peripheral artery disease in patients scheduled for infra-inguinal re-vascularization and selected based on a very limited number of inclusion criteria (all comers) aiming at maximization of external validity.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1200

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Switzerland
      • Fribourg, Switzerland, 1708
        • HFR Fribourg - Hôpital Cantonal / Kantonsspital
    • Canton of Zurich
      • Zurich, Canton of Zurich, Switzerland, 8091
        • University Hospital Zurich

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥18 years
  • Patients requiring endovascular angioplasty for PAD located below the inguinal ligament
  • Written informed consent obtained from participant or legal guardian prior to randomization; in patients requiring emergency interventional treatment who are temporarily not capable of providing informed consent, consent will be subsequently obtained after the procedure if strict conditions apply. These include the assessment of the presumed will and patient decree, and requires the allocation of an independent physician

Exclusion Criteria:

  • Pregnancy, breastfeeding, or planned pregnancy within the trial period or women of childbearing potential not using an adequate method of contraception
  • Patients with known intolerance or allergy to sirolimus
  • Participation in this or other clinical trials during the previous 3 months

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Sirolimus-coated group
Device: sirolimus-coated balloon catheter
angioplasty with sirolimus-coated balloon catheter
Active Comparator: Uncoated group
Device: uncoated balloon catheter
angioplasty with uncoated balloon catheter

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The primary efficacy outcome is a composite of two major adverse limb events (MALE): unplanned major amputation of the target limb or endovascular/surgical target lesion re-vascularization for critical limb ischemia occurring within one year.
Time Frame: One year
  • An unplanned major amputation is defined as any amputation above the ankle on the target limb, which was not planned or not expectable at the time of screening or randomization. Patients with scheduled amputation undergoing re-vascularization to improve wound healing are referred to as planned amputation and will not count for the primary outcome.
  • Critical limb ischemia is defined according to a Fontaine stage (classes III-IV) or according to criteria for a critical haemodynamic status, as defined in the ESC guidelines.
One year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Composite of unplanned (major or minor) index-limb amputations or any target lesion re-vascularization within one year of enrollment
Time Frame: One year

Unplanned major amputation is defined analogously to the definition used for the primary efficacy endpoint.

Unplanned minor amputation is defined as amputation below or at the level of the ankle, which was not planned or not expected at the time of randomization.
One year

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Death from all causes
Time Frame: up to five years
Death from all causes within 30 days, 180 days, one year, two years, and five years
up to five years
Serious adverse events (SAEs)
Time Frame: one year
Serious adverse events (SAEs) during initial hospitalization, within 180 days, and within 365 days
one year
Serious adverse device related events (SADE)
Time Frame: up to one month
Serious adverse device related events (SADE) during initial hospitalization
up to one month
A composite of all-cause death and MALE
Time Frame: one month
A composite of all-cause death and MALE within 30 days
one month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Nils Kucher

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Nils Kucher, Prof., University of Zurich

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 3, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 15, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 22, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 23, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 19, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 17, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SirPAD Trial

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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