Rationale and Design of the IN.PACT BTK Randomized Pilot Study: A Paclitaxel Drug-Coated Balloon vs Standard Percutaneous Transluminal Angioplasty for Infrapopliteal Chronic Total Occlusions

Antonio Micari, MD, PhD1;  Jeffrey J. Popma, MD2;  Francesco Liistro, MD3

Original Contribution

Rationale and Design of the IN.PACT BTK Randomized Pilot Study: A Paclitaxel Drug-Coated Balloon vs Standard Percutaneous Transluminal Angioplasty for Infrapopliteal Chronic Total Occlusions

Keywords

below the knee

chronic limb-threatening ischemia

Chronic Total Occlusion

Drug-coated balloon

paclitaxel

peripheral artery disease

June 2021

ISSN 2694-3026

Abstract

Objectives. This is a pilot feasibility study and the objective is to evaluate the safety and effectiveness of the investigational device, IN.PACT 014 drug-coated balloon (DCB), compared with standard percutaneous transluminal angioplasty (PTA) in the treatment of patients with chronic limb-threatening ischemia (CLTI) with chronic total occlusions (CTOs) of below-the-knee (BTK) arteries. Methods and Design. The IN.PACT BTK randomized study is a prospective, multicenter, randomized pilot study. Baseline angiography and duplex ultrasonography analyses were performed to confirm that participants met all anatomic and functional eligibility criteria. Successful predilation and strict intraprocedural angiographic and duplex sonographic criteria were conditions of enrollment and randomization. A total of 50 participants were enrolled and randomized 1:1 into DCB (n = 23) or control PTA (n = 27) treatment groups. The primary effectiveness endpoint is late lumen loss at 9 months post procedure. Secondary endpoints include a composite safety endpoint (freedom from device- and procedure-related mortality within 30 days, and freedom from major target-limb amputation and freedom from clinically driven target-lesion revascularization within 9 months after the procedure) and the rate of major adverse events. Participants are being followed through 5 years. All angiographic and duplex ultrasonography images are reviewed by independent core laboratories and all major adverse events are adjudicated by an independent clinical events committee. Discussion and Conclusion. This is a rigorously designed BTK trial in which participant selection and enrollment were a unique aspect, guided by a strict requirement for successful vessel preparation before randomization using explicit angiographic and duplex ultrasound parameters.

J CRIT LIMB ISCHEM 2021;1(2):E35-E44.

Key words: below the knee, chronic limb-threatening ischemia, chronic total occlusion, drug-coated balloon, paclitaxel,
peripheral artery disease

Please Log In To View

Lorem ipsum dolor sit amet consectetur, adipiscing elit maximus lobortis, porttitor tristique fames hendrerit. Duis sociosqu et egestas felis elit class nascetur nullam praesent, volutpat massa mi porta quisque condimentum habitant semper convallis, suscipit mollis cursus potenti maximus ligula commodo a. Erat blandit et ex accumsan enim quisque habitant, integer placerat parturient netus feugiat lorem montes aliquet, laoreet aptent adipiscing hendrerit mattis class. Integer libero fringilla dis nulla placerat sed accumsan, hendrerit ridiculus ultrices imperdiet posuere id nunc, magna orci tristique in quis auctor. Quam et class metus dictumst at vel suscipit cras eleifend enim, sodales volutpat ante duis lacinia rutrum dolor fringilla viverra, curabitur taciti cubilia semper aptent tristique magna hendrerit mi. Senectus tellus turpis hendrerit nisl quam vestibulum molestie, malesuada gravida efficitur dapibus in nam, quisque torquent porta imperdiet praesent nunc nulla, taciti orci elit rhoncus ad. Arcu etiam semper suscipit nec ante hac at, vitae libero porttitor morbi magna dolor mi, quis ligula ut tincidunt cras consectetur.

Augue velit ultrices donec natoque quis rhoncus pellentesque, accumsan malesuada neque nisl elit platea, suscipit elementum pretium curae ex montes. Semper auctor aptent quam dictum viverra hendrerit urna, morbi habitant augue ultricies amet convallis tellus, imperdiet cursus iaculis lectus pellentesque maecenas. Nulla a pharetra rutrum ante auctor maximus non nullam dapibus, justo aenean placerat netus congue rhoncus etiam tincidunt quisque hac, nostra inceptos montes commodo pretium laoreet magna ridiculus. Suscipit odio viverra eleifend porta pharetra accumsan netus finibus neque augue, proin ad dis lobortis tristique lorem ex mauris platea. Libero mollis litora laoreet fames non hac, habitant sociosqu euismod risus semper turpis hendrerit, commodo rutrum iaculis senectus potenti. Suspendisse etiam praesent facilisis bibendum dui volutpat non curabitur sem, morbi nam cras ullamcorper torquent consequat taciti rutrum nisl, lectus eget hac dictum auctor gravida tempus mauris. Senectus eros curabitur semper tortor adipiscing eget nunc, aptent dignissim vitae dolor scelerisque aliquam egestas, dictum ad ligula ultricies sodales nullam.

Quisque elementum quam litora et euismod augue himenaeos per ullamcorper, porta natoque imperdiet consequat cursus nunc mauris ad, adipiscing aliquet enim placerat in a eu parturient. A tristique cras montes donec nec suscipit arcu, et vestibulum rhoncus consequat sollicitudin dictumst quis accumsan, magnis quam dui feugiat platea laoreet. Mattis tempus volutpat ad quisque sed dictumst sodales nullam accumsan metus litora, nisi sapien eget facilisi iaculis blandit odio morbi malesuada pretium, donec ligula lacinia nostra leo conubia sem rutrum venenatis dignissim. Volutpat purus nascetur vulputate rhoncus fringilla lectus facilisi scelerisque, duis morbi id mollis facilisis feugiat malesuada ex natoque, mauris ultrices laoreet inceptos potenti porttitor orci.

Class tortor est efficitur platea lobortis turpis pretium, mattis fames natoque rutrum tellus tristique, luctus ut ligula adipiscing cubilia nascetur. Nam phasellus enim facilisis nostra semper non imperdiet dictum sollicitudin, eget velit habitasse ad sed bibendum torquent nascetur nibh augue, sit ligula metus ex neque odio massa lobortis. Magnis tellus eu ligula libero duis cubilia leo taciti habitant elit sociosqu, auctor mi fames suscipit potenti consectetur turpis semper torquent vivamus, imperdiet felis tempor habitasse elementum accumsan pellentesque rhoncus parturient curabitur. Tempor dapibus eros metus nulla duis aliquam posuere ridiculus nascetur quis, venenatis a urna ut consequat lobortis etiam rhoncus nec justo, sociosqu dignissim cras luctus dis viverra eget ex velit. Tincidunt aliquet lorem habitant blandit feugiat euismod orci lectus suspendisse, integer ut vulputate litora a posuere torquent pellentesque, efficitur cursus id facilisis volutpat sollicitudin nisl ligula. Mi mattis cras ante condimentum nisl inceptos euismod, commodo mauris montes eros felis pretium, proin tortor congue facilisis arcu volutpat. Eu pellentesque quam id potenti turpis dictum ultricies sed tortor phasellus lacinia, etiam tristique nostra suscipit dapibus nam vestibulum class elit nisl, mi iaculis lectus at justo inceptos massa dolor urna aenean.

References

1. Gray BH, Diaz-Sandoval LJ, Dieter RS, et al. SCAI expert consensus statement for infrapopliteal arterial intervention appropriate use. Catheter Cardiovasc Interv. 2014;84:539-445.

2. Gentile F, Lundberg G, Hultgren R. Outcome for endovascular and open procedures in infrapopliteal lesions for critical limb ischemia: registry based single center study. Eur J Vasc Endovasc Surg. 2016;52:643-649.

3. Giles KA, Pomposelli FB, Spence TL, et al. Infrapopliteal angioplasty for critical limb ischemia: relation of TransAtlantic InterSociety Consensus class to outcome in 176 limbs. J Vasc Surg. 2008;48:128-136.

4. Patel SD, Biasi L, Paraskevopoulos I, et al. Comparison of angioplasty and bypass surgery for critical limb ischaemia in patients with infrapopliteal peripheral artery disease. Br J Surg. 2016;103:1815-1822.

5. Popplewell MA, Davies HOB, Narayanswami J, et al. A comparison of outcomes in patients with infrapopliteal disease randomised to vein bypass or plain balloon angioplasty in the bypass vs angioplasty in severe ischaemia of the leg (BASIL) trial. Eur J Vasc Endovasc Surg. 2017;54:195-201.

6. Bosiers M, Scheinert D, Peeters P, et al. Randomized comparison of everolimus-eluting versus bare-metal stents in patients with critical limb ischemia and infrapopliteal arterial occlusive disease. J Vasc Surg. 2012;55:390-398.

7. Rastan A, Brechtel K, Krankenberg H, et al. Sirolimus-eluting stents for treatment of infrapopliteal arteries reduce clinical event rate compared to bare-metal stents: long-term results from a randomized trial. J Am Coll Cardiol. 2012;60:587-591.

8. Rastan A, Tepe G, Krankenberg H, et al. Sirolimus-eluting stents vs bare-metal stents for treatment of focal lesions in infrapopliteal arteries: a double-blind, multi-centre, randomized clinical trial. Eur Heart J. 2011;32:2274-2281.

9. Scheinert D, Katsanos K, Zeller T, et al. A prospective randomized multicenter comparison of balloon angioplasty and infrapopliteal stenting with the sirolimus-eluting stent in patients with ischemic peripheral arterial disease: 1-year results from the ACHILLES trial. J Am Coll Cardiol. 2012;60:2290-2295.

10. Fanelli F, Cannavale A, Corona M, Lucatelli P, Wlderk A, Salvatori FM. The “REBELLUM” — lower limb multilevel treatment with drug eluting balloon — randomized trial: 1-year results. J Cardiovasc Surg (Torino). 2014;55:207-216.

11. Liistro F, Porto I, Angioli P, et al. Drug-eluting balloon in peripheral intervention for below the knee angioplasty evaluation (DEBATE-BTK): a randomized trial in diabetic patients with critical limb ischemia. Circulation. 2013;128:615-621.

12. Mustapha JA, Brodmann M, Geraghty PJ, et al. Drug-coated vs uncoated percutaneous transluminal angioplasty in infrapopliteal arteries: six-month results of the Lutonix BTK trial. J Invasive Cardiol. 2019;31:205-211.

13. Siablis D, Kitrou PM, Spiliopoulos S, Katsanos K, Karnabatidis D. Paclitaxel-coated balloon angioplasty versus drug-eluting stenting for the treatment of infrapopliteal long-segment arterial occlusive disease: the IDEAS randomized controlled trial. JACC Cardiovasc Interv. 2014;7:1048-1056.

14. Zeller T, Baumgartner I, Scheinert D, et al. Drug-eluting balloon versus standard balloon angioplasty for infrapopliteal arterial revascularization in critical limb ischemia: 12-month results from the IN.PACT DEEP randomized trial. J Am Coll Cardiol. 2014;64:1568-1576.

15. Zeller T, Beschorner U, Pilger E, et al. Paclitaxel-coated balloon in infrapopliteal arteries: 12-month results from the BIOLUX P-II randomized trial (Biotronik’s first in man study of the Passeo-18 Lux drug-releasing PTA balloon catheter vs the uncoated Passeo-18 PTA balloon catheter in subjects requiring revascularization of infrapopliteal arteries). JACC Cardiovasc Interv. 2015;8:1614-1622.

16. Ozpak B, Bozok S, Cayir MC. Thirty-six-month outcomes of drug-eluting balloon angioplasty in the infrapopliteal arteries. Vascular. 2018;26:457-463.

17. Thabane L, Ma J, Chu R, et al. A tutorial on pilot studies: the what, why and how. BMC Med Res Methodol. 2010;10:1.

18. Brodmann M, Werner M, Meyer DR, et al. Sustainable antirestenosis effect with a low-dose drug-coated balloon: the ILLUMENATE European randomized clinical trial 2-year results. JACC Cardiovasc Interv. 2018;11:2357-2364.

19. Chen Z, Guo W, Jiang W, et al. IN.PACT SFA clinical study using the IN.PACT Admiral drug-coated balloon in a Chinese patient population. J Endovasc Ther. 2019;26:471-478.

20. Iida O, Soga Y, Urasawa K, et al. Drug-coated balloon vs standard percutaneous transluminal angioplasty for the treatment of atherosclerotic lesions in the superficial femoral and proximal popliteal arteries: one-year results of the MDT-2113 SFA Japan randomized trial. J Endovasc Ther. 2018;25:109-117.

21. Iida O, Soga Y, Urasawa K, et al. Drug-coated balloon versus uncoated percutaneous transluminal angioplasty for the treatment of atherosclerotic lesions in the superficial femoral and proximal popliteal artery: 2-year results of the MDT-2113 SFA Japan randomized trial. Catheter Cardiovasc Interv. 2019;93:664-672.

22. Krishnan P, Faries P, Niazi K, et al. Stellarex drug-coated balloon for treatment of femoropopliteal disease: twelve-month outcomes from the randomized ILLUMENATE pivotal and pharmacokinetic studies. Circulation. 2017;136:1102-1113.

23. Laird JA, Schneider PA, Jaff MR, et al. Long-term clinical effectiveness of a drug-coated balloon for the treatment of femoropopliteal lesions. Circ Cardiovasc Interv. 2019;12:e007702.

24. Laird JR, Schneider PA, Tepe G, et al. Durability of treatment effect using a drug-coated balloon for femoropopliteal lesions: 24-month results of IN.PACT SFA. J Am Coll Cardiol. 2015;66:2329-2338.

25. Micari A, Brodmann M, Keirse K, et al. Drug-coated balloon treatment of femoropopliteal lesions for patients with intermittent claudication and ischemic rest pain: 2-year results from the IN.PACT global study. JACC Cardiovasc Interv. 2018;11:945-953.

26. Rosenfield K, Jaff MR, White CJ, et al. Trial of a paclitaxel-coated balloon for femoropopliteal artery disease. N Engl J Med. 2015;373:145-153.

27. Schneider PA, Laird JR, Tepe G, et al. Treatment effect of drug-coated balloons is durable to 3 years in the femoropopliteal arteries: long-term results of the IN.PACT SFA randomized trial. Circ Cardiovasc Interv. 2018;11:e005891.

28. Schroe H, Holden AH, Goueffic Y, et al. Stellarex drug-coated balloon for treatment of femoropopliteal arterial disease — the ILLUMENATE global study: 12-month results from a prospective, multicenter, single-arm study. Catheter Cardiovasc Interv. 2018;91:497-504.

29. Schroeder H, Werner M, Meyer DR, et al. Low-dose paclitaxel-coated versus uncoated percutaneous transluminal balloon angioplasty for femoropopliteal peripheral artery disease: one-year results of the ILLUMENATE European randomized clinical trial (randomized trial of a novel paclitaxel-coated percutaneous angioplasty balloon). Circulation. 2017;135:2227-2236.

30. Tepe G, Laird J, Schneider P, et al. Drug-coated balloon versus standard percutaneous transluminal angioplasty for the treatment of superficial femoral and popliteal peripheral artery disease: 12-month results from the IN.PACT SFA randomized trial. Circulation. 2015;131:495-502.

31. Tepe G, Schnorr B, Albrecht T, et al. Angioplasty of femoral-popliteal arteries with drug-coated balloons: 5-year follow-up of the THUNDER trial. JACC Cardiovasc Interv. 2015;8:102-108.

32. Zeller T, Brodmann M, Micari A, et al. Drug-coated balloon treatment of femoropopliteal lesions for patients with intermittent claudication and ischemic rest pain. Circ Cardiovasc Interv. 2019;12:e007730.

33. Byrne RA, Joner M, Alfonso F, Kastrati A. Drug-coated balloon therapy in coronary and peripheral artery disease. Nat Rev Cardiol. 2014;11:13-23.

34. Fanelli F, Cannavale A, Boatta E, et al. Lower limb multilevel treatment with drug-eluting balloons: 6-month results from the DEBELLUM randomized trial. J Endovasc Ther. 2012;19:571-580.

35. Zeller T, Baumgartner I, Scheinert D, et al. IN.PACT Amphirion paclitaxel-eluting balloon versus standard percutaneous transluminal angioplasty for infrapopliteal revascularization of critical limb ischemia: rationale and protocol for an ongoing randomized controlled trial. Trials. 2014;15:63.

36. Spreen MI, Gremmels H, Teraa M, et al. Diabetes is associated with decreased limb survival in patients with critical limb ischemia: pooled data from two randomized controlled trials. Diabetes Care. 2016;39:2058-2064.

Affiliations and Disclosures