Clinical Performance of the Pantera Lux DCB Versus the Orsiro DES in Patients With "-Limus" DES-ISR. (BIOLUX-RCT)

• Percent diameter stenosis in-stent and in-segment [ Time Frame: After 6 months. ] [ Designated as safety issue: No ]
  Percent diameter stenosis is defined as the difference between reference vessel diameter and minimal lumen diameter divided by reference vessel diameter x100%. Angiographic parameters as evaluated by offline quantitative coronary angiography (QCA).
• Binary restenosis in-stent and in-segment [ Time Frame: After 6 months. ] [ Designated as safety issue: No ]
  Binary restenosis is defined as ≥50% lumen diameter stenosis as evaluated by offline quantitative coronary angiography (QCA).
• Mean lumen diameter in-stent and in-segment [ Time Frame: After 6 months. ] [ Designated as safety issue: No ]
• Type of reoccurrence according to Mehran classification [ Time Frame: After 6, 12 and 18 months. ] [ Designated as safety issue: No ]
  Type of reoccurrence according to Mehran classification (Mehran et al. Angiographic Patterns of In-Stent Restenosis, Classification and Implications for Long Term Outcome. Circulation 199; 100: 1872-1878) evaluated by offline quantitative coronary angiography (QCA).
• Target lesion failure (TLF) [ Time Frame: After 6 and 18 months. ] [ Designated as safety issue: Yes ]
  TLF is defined as a composite of cardiac death, any target vessel myocardial infarction, coronary artery bypass graft and clinically driven target lesion revascularization.
• Target vessel failure (TVF) [ Time Frame: After 6, 12 and 18 months. ] [ Designated as safety issue: Yes ]
  TVF is defined as a composite of cardiac death, any target vessel myocardial infarction, coronary artery bypass graft and clinically driven target vessel revascularization.
• Stent thrombosis [ Time Frame: After 6, 12 and 18 months. ] [ Designated as safety issue: Yes ]
  According to ARC definition (Cutlip et al., Clinical end points in coronary stent trials: a case for standardized definitions, Circulation 2007; 115: 2344-2351).
• Procedure success [ Time Frame: During hospital stay or 7 days after procedure, whichever came first. ] [ Designated as safety issue: Yes ]
  Procedure success defined as achievement of a final diameter stenosis of <30% by QCA, using any percutaneous method, without the occurrence of death, MI, or repeat revascularization of the target lesion during the hospital stay or 7 days after procedure, whichever came first.
• Device success [ Time Frame: 1 day (During procedure) ] [ Designated as safety issue: Yes ]

  Device success is defined as

  • successful delivery of the balloon/stent to the target lesion site in the coronary artery and
  • appropriate balloon inflation and deflation or stent deployment and
  • successful removal of the device
  • safe removal of the device in case of deployment failure

To determine in a randomized controlled trial whether percutaneous coronary intervention for "-limus" drug eluting stent in-stent restenosis with the Pantera Lux balloon catheter is angiographically non-inferior to percutaneous coronary intervention with the Orsiro stent after 6 months.

A prospective, multicenter, international, non-inferiority randomized controlled clinical trial. Up to 210 subjects will be block randomized 2:1 to receive the Pantera Lux balloon or the Orsiro stent and will be stratified according to diabetic status at screening.

Subjects treated with the Pantera Lux balloon will have a dual antiplatelet therapy for 3 months whereas subjects treated with the Orsiro stent will have a dual antiplatelet therapy for 6 months.

All patients will undergo an angiography after 6 months. Patients are clinically followed up after 3, 6, 12 and 18 months.

• Coronary Artery Disease
• Coronary Restenosis

• Device: Percutaneous coronary intervention

  140 patients meeting the inclusion criteria and none of the exclusion criteria are randomly selected and stratified according to diabetic status at screening are treated with the Pantera Lux drug coated balloon.

  Dual antiplatelet therapy (DAPT) for 3 months.

  Other Names:

  • Pantera Lux drug coated balloon
  • Paclitaxel
  • BTHC (Butyryltri-n-hexyl Citrate)
• Device: Percutaneous coronary intervention

  70 patients meeting the inclusion criteria and none of the exclusion criteria are randomly selected and stratified according to diabetic status at screening are treated with the Orsiro drug eluting stent.

  Dual antiplatelet therapy (DAPT) for 6 months.

  Other Names:

  • Orsiro drug eluting stent
  • Orsiro hybrid drug eluting stent system
  • Sirolimus eluting stent

• Experimental: Drug coated balloon
  Percutaneous coronary intervention with the Pantera Lux drug coated balloon.
  Intervention: Device: Percutaneous coronary intervention
• Active Comparator: Drug eluting stent
  Percutaneous coronary intervention with the Orsiro drug eluting stent.
  Intervention: Device: Percutaneous coronary intervention

• Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, Steg PG, Morel MA, Mauri L, Vranckx P, McFadden E, Lansky A, Hamon M, Krucoff MW, Serruys PW; Academic Research Consortium. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation. 2007 May 1;115(17):2344-51.
• Mehran R, Dangas G, Abizaid AS, Mintz GS, Lansky AJ, Satler LF, Pichard AD, Kent KM, Stone GW, Leon MB. Angiographic patterns of in-stent restenosis: classification and implications for long-term outcome. Circulation. 1999 Nov 2;100(18):1872-8.

Inclusion Criteria:

1. Subject has provided a written informed consent
2. Subject ≥ 18 years
3. Clinical evidence of ischemic heart disease and/or a positive functional study, stable or unstable angina pectoris or documented silent ischemia
4. Subject eligible for percutaneous coronary intervention
5. Subject acceptable candidate for coronary artery bypass surgery
6. Subject with a single in-stent restenotic lesion in a "-limus" drug eluting stent (sirolimus, everolimus, zotarolimus, biolimus): First reoccurrence of a single lesion after implantation of a "-limus" drug eluting stent to treat a de novo lesion
7. Subject must have no more than two lesions requiring treatment during BIOLUX RCT index procedure. These lesions must be in different vessel distributions. For example, if one target lesion is in the LAD, then the second target lesion must be present in either the LCX or RCA. The second lesion may not be in a branch vessel or distal to the target vessel location
8. Target reference vessel diameter (visual estimation): ≥ 2.0 and ≤ 4.0 mm
9. Target lesion length (visual estimation): ≥ 8.0 and ≤ 28.0 mm
10. Target lesion stenosis (visual estimation): > 50 % and < 100 %
11. Target lesion in a native coronary artery

Exclusion Criteria:

1. Planned (staged) interventional treatment in any vessel must be completed latest 30 days before BIOLUX RCT index procedure(s)
2. Subjects with a present dual antiplatelet therapy (DAPT) lasting longer than 90 days post BIOLUX RCT index procedure(s). This includes subjects taking phenprocoumon, warfarin or similar drugs.
3. Additional coronary lesions (restenotic or de novo) in the same vessel(s) or in a different coronary vessel which requires treatment within the next 18 months
4. Evidence of acute ST-segment-elevation myocardial infarction within 72 hours prior to index procedure according to the universal definition of myocardial infarction
5. Subjects with acute cardiac decompensation or acute cardiogenic shock
6. Subject with a life expectancy of less than 18 months
7. In the investigators opinion subject who will not be able to comply with the follow up requirements
8. Impaired renal function (excluded are subjects in need of dialysis or subjects with a creatinine level ≥ 221 µmol per liter (2.5 mg per deciliter) within 72 hours of the intended treatment)
9. Totally occluded coronary artery (Mehran classification IV and TIMI flow 0)
10. Thrombus in the target vessel
11. Target lesion involves a side branch > 2.0 mm in diameter
12. Target lesion located in left main coronary artery
13. Documented left ventricular ejection fraction (LVEF) ≤ 30%
14. Known allergies to: acetylsalicylic acid, clopidogrel, prasugrel, ticagrelor, heparin, contrast medium, sirolimus or similar drugs (i.e., ABT 578, biolimus, tacrolimus); CoCr, PLLA, silicon carbide
15. Subject is receiving oral or intravenous immunosuppressive therapy (e.g., inhaled steroids are not excluded) or has known life-limiting immunosuppressive or autoimmune disease (e.g., human immunodeficiency virus, systemic lupus erythematosus, but not including diabetes mellitus)
16. Subject currently enrolled in other investigational device or drug trial in which primary endpoint has not been reached
17. Pregnant and/or breast-feeding females or females who intend to become pregnant during the time of the study