PTA and Drug Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia

Phase 2

• Conditions: Peripheral Vascular Disease
• Interventions: Device: PTA with placement of paclitaxel-eluting stent; Device: PTA

• Registration Number: NCT00471289
• Lead Sponsor: Netherlands Society for Interventional Radiology

Brief Summary

The purpose of this study is to investigate the performance of paclitaxel-coated balloon expandable stainless steel coronary stent for the treatment of infrapopliteal stenoses and occlusions in patients with critical limb ischemia compared to percutaneous transluminal balloon angioplasty (PTA).

Detailed Description

Critical limb ischemia (CLI) is a serious condition that is becoming more and more common in the western world due to the growing percentage of elderly in the population and the rising incidence of diabetes. In about 40% of patients a stenosis or occlusion in the arteries below the level of the knee will be present. Restoration of blood flow is imperative to allow pain relief and tissue healing. Without revascularization patients with CLI are at risk for limb loss and potentially fatal complications such as sepsis.

In patients treated with percutaneous transluminal balloon angioplasty (PTA)significant restenosis is found in approximately 50% after 6 months.

In interventional cardiology a significant reduction in restenosis rates in coronary arteries has been found using drug eluting stents (DES), including the paclitaxel eluting stent (TAXUS, Boston Scientific). DES locally deliver drugs (e.g. paclitaxel) that interfere with the restenosis process.

Using DES in treating below the knee (infrapopliteal) arterial lesions in patients with CLI may improve patency and clinical outcome.

Comparison:

Treatment of below the knee arterial lesions in patients with CLI with PTA and DES compared to only PTA.

Study Timeline

• Study First Submitted: 2007-05-07
• Study First Submitted QC: 2007-05-07
• Study First Posted: 2007-05-09
• Study Start: 2007-08
• Primary Completion: 2013-09
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-15
• Last Update Posted: 2020-09-16
• Study Completion: 2023-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 144

Inclusion Criteria

• Written informed consent
• Age > 18 years
• If female patient with child bearing potential, patient may not be pregnant at the study entry and must utilize reliable birth control for the duration of her participation into the study
• Patient is willing and able to comply with the specified follow-up evaluation
• Critical Limb Ischaemia, this is Fontaine stage III (ischaemic rest pain) and IV (ischaemic ulcers or gangrene) or Rutherford category 4 (ischaemic rest pain), 5 (minor tissue loss) or 6 (major tissue loss)
• Stenotic (>50% luminal loss) or occluded infrapopliteal artery, including the tibiofibular trunk, the anterior tibial artery, the posterior tibial artery and the peroneal artery, with a lesion length ≤ 60 mm
• Artery to be treated with a diameter more tham or equal to 2mm and less than or equal to 4mm
• Patent common iliac, external iliac, superficial femoral and popliteal artery on the ipsilateral side prior to randomisation, possibly after treatment during the same session
• At least one patent crural (anterior tibial, posterior tibial or peroneal) artery with expected unobstructed runoff to ankle level after treatment

Exclusion Criteria

• Acute limb ischaemia
• Subacute limb ischaemia which requires thrombolysis as first treatment modality
• Active bleeding or bleeding diathesis
• Recent (less than 3 months) hemorrhagic stroke or other any other CNS abnormality with increased risk of haemorrhage, such as intracranial neoplasm, arteriovenous malformation, intracranial aneurysm or aneurysm repair
• Gastrointestinal or genitourinary bleeding of clinical significance within the previous 6 weeks before treatment
• Aneurysm in common femoral, superficial femoral or popliteal artery on the ipsilateral side
• Revascularization involving the same limb within 30 days prior to the index procedure or planned revascularization of the same limb within 30 days of the index procedure
• Previous implanted stent at the index site
• Life expectancy of less than 6 months or other factors making clinical follow-up difficult
• Known allergy to acetylsalicylic acid (aspirin), clopidogrel, heparin or paclitaxel
• Known allergy to contrast media
• Known heparin induced thrombocytopenia (HIT type 2)
• Patient unable or unwilling to tolerate anticoagulant, anti-platelet therapy or contrast media
• Creatinine clearance < 20 ml/min (as derived from Cockcroft-Gault or MDRD formula)unless patient is on hemodialysis
• Aneurysm in common femoral, superficial femoral or popliteal artery on the ipsilateral side
• Severely calcified lesions with expected resistance to stenting
• Poor inflow due to ipsilateral stenoses or occlusions of the iliac or femoropopliteal arteries that cannot be treated during the same session
• Significant vessel tortuosity or other parameters prohibiting access to the lesions and/or delivery of the stent
• Patients without (expected) distal runoff to the index site
• Previous implanted stent at the index site

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	PTA with placement of paclitaxel-eluting stent	PTA with primary placement of Drug (paclitaxel) Eluting Stent
2	PTA	PTA

Primary Outcome Measures

Name	Time	Method
The primary endpoint will be primary patency of the treated site at 6 months. Primary patency is defined as <50% loss of luminal diameter at the treated site on CT arteriography (CTA) without re-intervention in the interim.	6 months

Secondary Outcome Measures

Name	Time	Method
Primary patency of the treated sites at 3, 6 and 12 months after intervention assessed by duplex sonography (binary patency, <50% stenosis defined as PSV ratio <2.0)	3, 6, 12 months
Minor amputation (below the ankle excluding the toes) of the trial leg at 3, 6 and 12 months.	yearly up to 10 years after treatment	From 2 to 5 years during outpatient clinic visits From 5 to 10 years yearly evaluation of patient charts
Death.	3, 6, 12 months
Clinical assessment primarily by Rutherford score for peripheral arterial disease	2, 3, 4 and 5 years after treatment	Clinical assessment outpatient clinic
Major amputation (at or above the ankle) of treated limb	yearly up to 10 years after treatment	Assessment up to 5 years after treatment during outpatient clinic visits From 5 to 10 years by means of yearly evaluation of patient charts
Infrapopliteal surgical bypass of the trial leg at 3, 6 and 12 months.	3, 6, 12 months
Infrapopliteal endovascular re-intervention of the trial leg at 3, 6 and 12 months.	3, 6, 12 months
Target lesion patency by means of duplex sonography	2, 3, 4 and 5 years after treatment	During outpatient clinic visits
Endovascular or surgical re-intervention of target lesion	3, 6, 12 months, 2,3,4 and 5 years after inclusion	Follow-up until first re-intervention of target lesion
Clinical evaluation of the treated ischemic leg at 3, 6 and 12 months.	3, 6, 12 months
Major amputation (at or above the ankle) of the trial leg at 3, 6 and 12 months	3, 6, 12 months
Peri-procedural (within 30 days) complications.	30 days

Trial Locations

Locations (3)

Sint Antonius Ziekenhuis; 🇳🇱 Nieuwegein, Utrecht, Netherlands

HagaZiekenhuis, location Leyweg; 🇳🇱 The Hague, ZH, Netherlands

University Medical Center Utrecht (UMCU); 🇳🇱 Utrecht, Netherlands