Efficacy Study of Paclitaxel-eluting Balloon, -Stent vs. Plain Angioplasty for Drug-eluting Stent Restenosis (ISAR-DESIRE-3)

• In-segment minimal luminal diameter [ Time Frame: 6-8 months ] [ Designated as safety issue: No ]
• In-segment binary angiographic restenosis [ Time Frame: 6-8 months ] [ Designated as safety issue: No ]
• Combined incidence of death or myocardial infarction [ Time Frame: 1 and 2 years ] [ Designated as safety issue: Yes ]
• Incidence of thrombosis [ Time Frame: 1 and 2 years ] [ Designated as safety issue: Yes ]

The purpose of this randomized study is to determine which treatment option, either paclitaxel-eluting balloon, paclitaxel-eluting stent or plain balloon angioplasty is the most effective in the treatment of restenosis after implantation of "Limus"-eluting stents, (LES).

The use of drug-eluting stents (DES) has led to a drastic reduction of restenosis rates compared to bare metal stents (BMS), but 5% to 10% of patients receiving DES are still in need of revascularization of the treated vessel. Two important families of drugs are used for stent coating: paclitaxel belonging to the taxane family, and the "limus"-family such as sirolimus, everolimus, zotarolimus, biolimus A9 and pimecrolimus.

Data regarding the optimal treatment of in-DES-restenosis is very limited. Implanting a new DES for in-DES-restenosis has been reported to be associated with re-restenosis rates as high as 43%. Several recent well published studies have shown a substantial reduction of restenosis using paclitaxel-eluting balloons (PEB) for de-novo lesions and BMS-restenotic lesions.

The objective of this randomized trial is to assess the hypothesis, that PEB are non-inferior to paclitaxel-eluting-stents (PES) for restenosis in "limus"-eluting-stents (LES), and both, PEB and PES, are superior to plain angioplasty in patients with restenosis after initial LES implantation.

• Heart Disease
• Ischemia
• Restenosis

• Device: Taxus stent
  Implantation of paclitaxel-eluting stent
• Device: SeQuent Please
  Dilation with SeQuent Please (paclitaxel-eluting balloon)
• Device: Conventional Balloon Catheter
  Ryuijin, Trek

• Experimental: Paclitaxel-eluting stent
  Paclitaxel-eluting stent (Taxus)
  Intervention: Device: Taxus stent
• Active Comparator: Plain Balloon
  plain balloon angioplasty
  Intervention: Device: Conventional Balloon Catheter
• Experimental: Paclitaxel-eluting balloon
  SeQuent Please
  Intervention: Device: SeQuent Please

• Unverdorben M, Vallbracht C, Cremers B, Heuer H, Hengstenberg C, Maikowski C, Werner GS, Antoni D, Kleber FX, Bocksch W, Leschke M, Ackermann H, Boxberger M, Speck U, Degenhardt R, Scheller B. Paclitaxel-coated balloon catheter versus paclitaxel-coated stent for the treatment of coronary in-stent restenosis. Circulation. 2009 Jun 16;119(23):2986-94. Epub 2009 Jun 1.
• Byrne RA, Neumann FJ, Mehilli J, Pinieck S, Wolff B, Tiroch K, Schulz S, Fusaro M, Ott I, Ibrahim T, Hausleiter J, Valina C, Pache J, Laugwitz KL, Massberg S, Kastrati A; ISAR-DESIRE 3 investigators. Paclitaxel-eluting balloons, paclitaxel-eluting stents, and balloon angioplasty in patients with restenosis after implantation of a drug-eluting stent (ISAR-DESIRE 3): a randomised, open-label trial. Lancet. 2013 Feb 9;381(9865):461-7. doi: 10.1016/S0140-6736(12)61964-3. Epub 2012 Dec 1.

Inclusion Criteria:

1. Patients with ischemic symptoms or evidence of myocardial ischemia in the presence of ≥ 50% restenosis after prior implantation of LES in native coronary vessels.
2. Written, informed consent by the patient or her/his legally-authorized representative for participation in the study.
3. In women with childbearing potential a negative pregnancy test is mandatory.

Exclusion Criteria:

1. Age < 18 years.
2. Cardiogenic shock.
3. Acute ST-elevation myocardial infarction within 48 hours from symptom onset.
4. Target lesion located in the left main trunk or bypass graft.
5. Target lesion located in small vessel (vessel size < 2.0 mm).
6. Malignancies or other comorbid conditions (for example severe liver, renal and pancreatic disease) with life expectancy less than 12 months or that may result in protocol non-compliance.
7. Severe renal insufficiency (glomerular filtration rate ≤ 30 ml/min).
8. Contraindications to antiplatelet therapy, paclitaxel, stainless steel, cobalt, chrome.
9. Pregnancy (present, suspected or planned) or positive pregnancy test.
10. Previous enrollment in this trial.
11. Patient's inability to fully comply with the study protocol.