Clinical Performance of the Pantera Lux Balloon Versus the Orsiro Stent in Patients With In-stent Restenosis. (BIOLUX-RCT)

• ClinicalTrials.gov Identifier: NCT01651390
• Recruitment Status: Completed
• First Posted: July 27, 2012
• Last Update Posted: September 26, 2016
• Sponsor: Biotronik AG
• Information provided by (Responsible Party): Biotronik AG

Tracking Information

• First Submitted Date: July 24, 2012
• First Posted Date: July 27, 2012
• Last Update Posted Date: September 26, 2016
• Study Start Date: June 2012
• Actual Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 28, 2013)

Late lumen loss (in-stent) [ Time Frame: After 6 months. ]

In-stent late lumen loss is defined as the difference between minimal luminal diameter after procedure and at 6 months, as evaluated by offline quantitative coronary angiography (QCA). In-stent: Pantera Lux balloon: In-stent is defined as from (proximal) shoulder to (distal) shoulder of the dilated balloon. Orsiro stent: In-stent is defined as from (proximal) edge to (distal) edge of the implanted Orsiro stent.

Original Primary Outcome Measures (submitted: July 26, 2012)

Late lumen loss (in-stent) [ Time Frame: After 6 months. ]

Late lumen loss is defined as the difference between in-stent respective in-segment minimal luminal diameter after procedure and at 6 months, as evaluated by offline quantitative coronary angiography (QCA). In-stent: Pantera Lux balloon: In-stent is defined as from (proximal) shoulder to (distal) shoulder of the dilated balloon. Orsiro stent: In-stent is defined as from (proximal) edge to (distal) edge of the implanted Orsiro stent.

Current Secondary Outcome Measures (submitted: June 28, 2013)

• Percent diameter stenosis in-stent and in-segment [ Time Frame: After 6 months. ]
  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 QCA. In-segment: Pantera Lux balloon: In-segment is defined as in-stent plus 5 mm distal and 5 mm proximal. Orsiro stent: In-segment is defined as in-stent plus 5 mm distal and 5 mm proximal.
• Binary restenosis in-stent and in-segment [ Time Frame: After 6 months. ]
  Binary restenosis is defined as ≥50% lumen diameter stenosis as evaluated by offline QCA.
• Mean lumen diameter in-stent and in-segment [ Time Frame: After 6 months. ]
  Mean minimum lumen diameter derived from two orthogonal views as evaluated by offline QCA.
• Type of reoccurrence according to Mehran classification [ Time Frame: After 6, 12 and 18 months. ]
  Type of reoccurrence according to Mehran classification (Mehran et al. Circulation 199; 100: 1872-1878) evaluated by offline QCA.
• Target lesion failure (TLF) [ Time Frame: After 6 and 18 months. ]
  TLF is defined as a composite of cardiac death, any target vessel myocardial infarction (MI), coronary artery bypass graft (CABG) and clinically driven target lesion revascularization (TLR).
• Target vessel failure (TVF) [ Time Frame: After 6, 12 and 18 months. ]
  TVF is defined as a composite of cardiac death, any target vessel myocardial infarction, coronary artery bypass graft and clinically driven target vessel revascularization (TVR).
• Stent thrombosis [ Time Frame: After 6, 12 and 18 months. ]
  According to Academic Research Consortium (ARC) definition (Cutlip et al. Circulation 2007; 115: 2344-2351).
• Procedure success [ Time Frame: During hospital stay or 7 days after procedure, whichever came first. ]
  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) ]
  Successful delivery of the balloon or stent to the target lesion site in the coronary artery; and appropriate balloon inflation and deflation or stent deployment; and successful removal of the balloon or the delivery system.

Original Secondary Outcome Measures (submitted: July 26, 2012)

• Percent diameter stenosis in-stent and in-segment [ Time Frame: After 6 months. ]
  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. ]
  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. ]
• Type of reoccurrence according to Mehran classification [ Time Frame: After 6, 12 and 18 months. ]
  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. ]
  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. ]
  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. ]
  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. ]
  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) ]
  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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Clinical Performance of the Pantera Lux Balloon Versus the Orsiro Stent in Patients With In-stent Restenosis.
• Official Title: BIOLUX RCT - Clinical Performance of the Pantera LUX Paclitaxel Releasing Balloon Versus the Drug Eluting Orsiro Hybrid Stent System in Patients With In-stent Restenosis - a Randomized Controlled Trial
• Brief Summary: To determine in a randomized controlled trial (RCT) whether percutaneous coronary intervention - in patients with in-stent restenosis in either bare metal stents or drug eluting stents - with the Pantera Lux balloon is angiographically non-inferior to percutaneous intervention with the Orsiro stent 6 months post-procedure.

Detailed Description

This clinical investigation is an international, multi-center, randomized controlled trial with angiographic follow up at 6 months. Clinical follow ups will take place at 6, 12 and 18 months.

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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Coronary Artery Disease
• Coronary Restenosis

Intervention

• Device: Percutaneous coronary intervention
  Up to 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.
  Other Names:

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

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

Study Arms

• 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

Publications *

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 2, 2015): 231
• Original Estimated Enrollment (submitted: July 26, 2012): 210
• Actual Study Completion Date: July 2016
• Actual Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 an in-stent restenotic lesion* in either a bare metal stent or drug eluting stents (Mehran class I, II, III, IV - Mehran et al. Circulation 199; 100: 1872-1878). *Target lesion
7. Subjects with a maximum of 2 target lesions. In case of 2 target lesions, both lesions must be either in bare metal stents or drug eluting stents, and must treated during the same session with the same type of device as per randomization outcome, e.g. drug eluting stent.
8. Target reference vessel diameter (visual estimation): ≥ 2.0 and ≤ 4.0 mm
9. Target lesion length (visual estimation): ≥ 6.0 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 the same vessel(s) as the target lesion(s) within 30 days pre- and/or post BIOLUX RCT index procedure.
2. Evidence of acute ST-segment-elevation myocardial infarction within 48 hours prior to index procedure according to the universal definition of myocardial infarction
3. Subjects with acute cardiac decompensation or acute cardiogenic shock
4. Subject with a life expectancy of less than 18 month
5. In the investigators opinion subject who will not be able to comply with the follow up requirements
6. 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)
7. Thrombus in the target vessel
8. Target lesion located in left main coronary artery
9. Documented left ventricular ejection fraction (LVEF) ≤ 30%
10. 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
11. 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)
12. Subject currently enrolled in other investigational device or drug trial in which primary endpoint has not been reached
13. Pregnant and/or breast-feeding females or females who intend to become pregnant during the time of the study
14. Previously enrolled in this trial

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany, Latvia

Administrative Information

• NCT Number: NCT01651390
• Other Study ID Numbers: C1105
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Biotronik AG
• Study Sponsor: Biotronik AG
• Collaborators: Not Provided

Investigators

• Principal Investigator: Christoph K Naber, MD; Contilia Heart- and Vascular Center, Elisabeth Krankenhaus, Klara-Kopp-Weg 1, 45138 Essen, Germany

• PRS Account: Biotronik AG
• Verification Date: September 2016