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

Percutaneous Transluminal Balloon Angioplasty (PTA) and Drug Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Peripheral Vascular Disease
• Intervention / Treatment: Device: PTA with placement of paclitaxel-eluting stent; Device: 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 Type: Interventional
• Enrollment (Actual): 144
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • University Medical Center Utrecht (UMCU)
  • Utrecht
    • Nieuwegein, Utrecht, Netherlands
      • Sint Antonius Ziekenhuis
  • ZH
    • The Hague, ZH, Netherlands, 2545CH
      • HagaZiekenhuis, location Leyweg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; PTA with primary placement of Drug (paclitaxel) Eluting Stent	Device: PTA with placement of paclitaxel-eluting stent; PTA with placement of paclitaxel-eluting stent
Active Comparator: 2; PTA	Device: PTA; PTA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
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
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
Minor amputation (below the ankle excluding the toes) of the trial leg at 3, 6 and 12 months.		3, 6, 12 months
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
Peri-procedural (within 30 days) complications.		30 days
Death.		3, 6, 12 months
Clinical assessment primarily by Rutherford score for peripheral arterial disease	Clinical assessment outpatient clinic	2, 3, 4 and 5 years after treatment
Target lesion patency by means of duplex sonography	During outpatient clinic visits	2, 3, 4 and 5 years after treatment
Major amputation (at or above the ankle) of treated limb	Assessment up to 5 years after treatment during outpatient clinic visits From 5 to 10 years by means of yearly evaluation of patient charts	yearly up to 10 years after treatment
Minor amputation (below the ankle excluding the toes) of the trial leg at 3, 6 and 12 months.	From 2 to 5 years during outpatient clinic visits From 5 to 10 years yearly evaluation of patient charts	yearly up to 10 years after treatment
Endovascular or surgical re-intervention of target lesion	Follow-up until first re-intervention of target lesion	3, 6, 12 months, 2,3,4 and 5 years after inclusion

Collaborators and Investigators

• Sponsor: Netherlands Society for Interventional Radiology
• Investigators: Principal Investigator: Hans Van Overhagen, MD PhD, HagaZiekenhuis Dept. of Radiology

Publications and helpful links

General Publications

• Adam DJ, Beard JD, Cleveland T, Bell J, Bradbury AW, Forbes JF, Fowkes FG, Gillepsie I, Ruckley CV, Raab G, Storkey H; BASIL trial participants. Bypass versus angioplasty in severe ischaemia of the leg (BASIL): multicentre, randomised controlled trial. Lancet. 2005 Dec 3;366(9501):1925-34. doi: 10.1016/S0140-6736(05)67704-5.
• Tsetis D, Belli AM. The role of infrapopliteal angioplasty. Br J Radiol. 2004 Dec;77(924):1007-15. doi: 10.1259/bjr/97382129.
• Wiskirchen J, Schober W, Schart N, Kehlbach R, Wersebe A, Tepe G, Claussen CD, Duda SH. The effects of paclitaxel on the three phases of restenosis: smooth muscle cell proliferation, migration, and matrix formation: an in vitro study. Invest Radiol. 2004 Sep;39(9):565-71. doi: 10.1097/01.rli.0000133815.22434.55.
• Serruys PW, Kutryk MJ, Ong AT. Coronary-artery stents. N Engl J Med. 2006 Feb 2;354(5):483-95. doi: 10.1056/NEJMra051091. No abstract available.
• Aoki J, Colombo A, Dudek D, Banning AP, Drzewiecki J, Zmudka K, Schiele F, Russell ME, Koglin J, Serruys PW; TAXUS II Study Group. Peristent remodeling and neointimal suppression 2 years after polymer-based, paclitaxel-eluting stent implantation: insights from serial intravascular ultrasound analysis in the TAXUS II study. Circulation. 2005 Dec 20;112(25):3876-83. doi: 10.1161/CIRCULATIONAHA.105.558601. Epub 2005 Dec 12.
• Kudo T, Chandra FA, Ahn SS. The effectiveness of percutaneous transluminal angioplasty for the treatment of critical limb ischemia: a 10-year experience. J Vasc Surg. 2005 Mar;41(3):423-35; discussion 435. doi: 10.1016/j.jvs.2004.11.041.
• Management of peripheral arterial disease (PAD). TransAtlantic Inter-Society Consensus (TASC). Section D: chronic critical limb ischaemia. Eur J Vasc Endovasc Surg. 2000 Jun;19 Suppl A:S144-243. No abstract available.
• Jensen SA, Vatten LJ, Myhre HO. The prevalence of chronic critical lower limb ischaemia in a population of 20,000 subjects 40-69 years of age. Eur J Vasc Endovasc Surg. 2006 Jul;32(1):60-5. doi: 10.1016/j.ejvs.2005.12.022. Epub 2006 Mar 2.
• Black JH 3rd, LaMuraglia GM, Kwolek CJ, Brewster DC, Watkins MT, Cambria RP. Contemporary results of angioplasty-based infrainguinal percutaneous interventions. J Vasc Surg. 2005 Nov;42(5):932-9. doi: 10.1016/j.jvs.2005.06.024.
• Sigala F, Menenakos Ch, Sigalas P, Baunach Ch, Langer S, Papalambros E, Hepp W. Transluminal angioplasty of isolated crural arterial lesions in diabetics with critical limb ischemia. Vasa. 2005 Aug;34(3):186-91. doi: 10.1024/0301-1526.34.3.186.
• Hynes N, Mahendran B, Manning B, Andrews E, Courtney D, Sultan S. The influence of subintimal angioplasty on level of amputation and limb salvage rates in lower limb critical ischaemia: a 15-year experience. Eur J Vasc Endovasc Surg. 2005 Sep;30(3):291-9. doi: 10.1016/j.ejvs.2005.04.020.
• Eskelinen E, Alback A, Roth WD, Lappalainen K, Keto P, Railo M, Eskelinen A, Lepantalo M. Infra-inguinal percutaneous transluminal angioplasty for limb salvage: a retrospective analysis in a single center. Acta Radiol. 2005 Apr;46(2):155-62. doi: 10.1080/02841850510022705.
• Atar E, Siegel Y, Avrahami R, Bartal G, Bachar GN, Belenky A. Balloon angioplasty of popliteal and crural arteries in elderly with critical chronic limb ischemia. Eur J Radiol. 2005 Feb;53(2):287-92. doi: 10.1016/j.ejrad.2004.02.016.
• Matsagas MI, Rivera MA, Tran T, Mitchell A, Robless P, Davies AH, Geroulakos G. Clinical outcome following infra-inguinal percutaneous transluminal angioplasty for critical limb ischemia. Cardiovasc Intervent Radiol. 2003 May-Jun;26(3):251-5. doi: 10.1007/s00270-003-0007-z.
• Molloy KJ, Nasim A, London NJ, Naylor AR, Bell PR, Fishwick G, Bolia A, Thompson MM. Percutaneous transluminal angioplasty in the treatment of critical limb ischemia. J Endovasc Ther. 2003 Apr;10(2):298-303. doi: 10.1177/152660280301000220.
• Haider SN, Kavanagh EG, Forlee M, Colgan MP, Madhavan P, Moore DJ, Shanik GD. Two-year outcome with preferential use of infrainguinal angioplasty for critical ischemia. J Vasc Surg. 2006 Mar;43(3):504-512. doi: 10.1016/j.jvs.2005.11.016.
• Spreen MI, Martens JM, Knippenberg B, van Dijk LC, de Vries JPM, Vos JA, de Borst GJ, Vonken EPA, Bijlstra OD, Wever JJ, Statius van Eps RG, Mali WPTM, van Overhagen H. Long-Term Follow-up of the PADI Trial: Percutaneous Transluminal Angioplasty Versus Drug-Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia. J Am Heart Assoc. 2017 Apr 14;6(4):e004877. doi: 10.1161/JAHA.116.004877.
• Spreen MI, Martens JM, Hansen BE, Knippenberg B, Verhey E, van Dijk LC, de Vries JP, Vos JA, de Borst GJ, Vonken EJ, Wever JJ, Statius van Eps RG, Mali WP, van Overhagen H. Percutaneous Transluminal Angioplasty and Drug-Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia (PADI) Trial. Circ Cardiovasc Interv. 2016 Feb;9(2):e002376. doi: 10.1161/CIRCINTERVENTIONS.114.002376.
• Martens JM, Knippenberg B, Vos JA, de Vries JP, Hansen BE, van Overhagen H; PADI Trial Group. Update on PADI trial: percutaneous transluminal angioplasty and drug-eluting stents for infrapopliteal lesions in critical limb ischemia. J Vasc Surg. 2009 Sep;50(3):687-9. doi: 10.1016/j.jvs.2009.04.073.

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): September 1, 2013
• Study Completion (Anticipated): March 1, 2023

Study Registration Dates

• First Submitted: May 7, 2007
• First Submitted That Met QC Criteria: May 7, 2007
• First Posted (Estimate): May 9, 2007

Study Record Updates

• Last Update Posted (Actual): September 16, 2020
• Last Update Submitted That Met QC Criteria: September 15, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Peripheral arterial disease; Stents; PAD; Paclitaxel; Interventional Radiology; CLI; Critical Limb Ischemia; DES; Drug Eluting Stents; Infrapopliteal; TAXUS; Infragenicular
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Vascular Diseases; Ischemia; Peripheral Arterial Disease; Peripheral Vascular Diseases; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: PADI/200601