Peripheral Arterial DiseaseNCT04238546
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
A study testing sirolimus-coated balloon catheter and uncoated balloon catheter in people with Peripheral Arterial Disease, run by Nils Kucher at 2 sites in Switzerland.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Peripheral Arterial Disease
- What is being tested?
- sirolimus-coated balloon catheter and uncoated balloon catheter
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,200 participants
- Where
- 2 sitesSwitzerland
- Study dates
- 3 Nov 2020to 31 Dec 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
Switzerland2 sites
HFR Fribourg - Hôpital Cantonal / Kantonsspital
Fribourg, 1708
University hospital zurich
Zurich, Canton of Zurich, 8091
About this study
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.
Read the 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.
- Conditions
- Peripheral Arterial Disease
- Being tested
- sirolimus-coated balloon catheter, uncoated balloon catheter
- Medical subject headings
- Peripheral Arterial Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sirolimus-coated balloon catheterDevice
angioplasty with sirolimus-coated balloon catheter
uncoated balloon catheterDevice
angioplasty with uncoated balloon catheter
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus-coated group | Experimental | Not described Receives: Device: sirolimus-coated balloon catheter |
| Uncoated group | Active comparator | Not described Receives: Device: uncoated balloon catheter |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
- 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.
Measured: One year
Secondary outcomes (1)
Composite of unplanned (major or minor) index-limb amputations or any target lesion re-vascularization within one year of enrollment
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.
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2020
- Study start3 Nov 2020
- Primary completion31 Dec 2025
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Peripheral Arterial DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nils Kucher
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Nils Kucher, University of Zurich
- Investigators
- Nils Kucher, Prof., Principal investigator, University of Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04238546
- Sponsor's protocol ID
- SirPAD Trial
- Status last verified
- Feb 2026
- First submitted
- 15 Jan 2020
- Last updated
- 19 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tsaftaridis N, Wolf S, Engelberger RP, Held U, Fumagalli RM, Grigorean A, Munger M, Sebastian T, Ledoux J, Voci D, Periard D, Madaro B, Cardi S, Rimann L, Kucher N, Barco S; SirPAD Investigators. Sirolimus-Coated Balloon Angioplasty for Femoropopliteal Artery Disease Without Tissue Loss: A Secondary Analysis of the SirPAD Trial. J Am Coll Cardiol. 2026 Oct 5:S0735-1097(26)07861-7. doi: 10.1016/j.jacc.2026.09.037. Online ahead of print.
PubMed 42909452Barco S, Engelberger RP, Held U, Fumagalli RM, Grigorean A, Hayoz D, Munger M, Sebastian T, Stadler R, Voci D, Wolf S, Baumann F, Tritschler T, von Stempel C, Periard D, Kucher N; SirPAD Investigators. Sirolimus-Coated Balloon Angioplasty for Infrainguinal Artery Disease. N Engl J Med. 2026 Aug 6;395(6):561-570. doi: 10.1056/NEJMoa2600360. Epub 2026 Mar 30.
PubMed 41911022Barco S, Sebastian T, Voci D, Engelberger RP, Grigorean A, Holy E, Leeger C, Munger M, Periard D, Probst E, Spescha R, Held U, Kucher N. 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: a structured protocol summary of the "SirPAD" randomized controlled trial. Trials. 2022 Apr 21;23(1):334. doi: 10.1186/s13063-022-06242-8.
PubMed 35449070
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04238546
- Acronym / sponsor ID
- SirPAD Trial
- Conditions
- Peripheral Arterial Disease
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 1,200 participants (estimated)
- Lead sponsor
- Nils KucherUniversity, hospital or other
- Study start
- 3 Nov 2020 (actual)
- Primary completion
- 31 Dec 2025 (actual)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 23 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sirolimus-coated group | Experimental | Device: sirolimus-coated balloon catheter |
| Uncoated group | Active comparator | Device: uncoated balloon catheter |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sirolimus-coated balloon catheterangioplasty with sirolimus-coated balloon catheter | Device | Sirolimus-coated group |
| uncoated balloon catheterangioplasty with uncoated balloon catheter | Device | Uncoated group |
Primary outcome
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.
1 secondary outcome
Composite of unplanned (major or minor) index-limb amputations or any target lesion re-vascularization within one year of enrollment
Time frame: One year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2026.
- Derived from this study: PubMed 42909452Tsaftaridis N, Wolf S, Engelberger RP, Held U, Fumagalli RM, Grigorean A, Munger M, Sebastian T, Ledoux J, Voci D, Periard D, Madaro B, Cardi S, Rimann L, Kucher N, Barco S; SirPAD Investigators. Sirolimus-Coated Balloon Angioplasty for Femoropopliteal Artery Disease Without Tissue Loss: A Secondary Analysis of the SirPAD Trial. J Am Coll Cardiol. 2026 Oct 5:S0735-1097(26)07861-7. doi: 10.1016/j.jacc.2026.09.037. Online ahead of print.
- Derived from this study: PubMed 41911022Barco S, Engelberger RP, Held U, Fumagalli RM, Grigorean A, Hayoz D, Munger M, Sebastian T, Stadler R, Voci D, Wolf S, Baumann F, Tritschler T, von Stempel C, Periard D, Kucher N; SirPAD Investigators. Sirolimus-Coated Balloon Angioplasty for Infrainguinal Artery Disease. N Engl J Med. 2026 Aug 6;395(6):561-570. doi: 10.1056/NEJMoa2600360. Epub 2026 Mar 30.
- Derived from this study: PubMed 35449070Barco S, Sebastian T, Voci D, Engelberger RP, Grigorean A, Holy E, Leeger C, Munger M, Periard D, Probst E, Spescha R, Held U, Kucher N. 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: a structured protocol summary of the "SirPAD" randomized controlled trial. Trials. 2022 Apr 21;23(1):334. doi: 10.1186/s13063-022-06242-8.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nils Kucher, Prof. principal investigator
University of Zurich
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing sirolimus-coated balloon catheter and uncoated balloon catheter in people with Peripheral Arterial Disease, run by Nils Kucher at 2 sites in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 19 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04238546, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2026.