Paclitaxel Releasing Balloon in Patients Presenting With In-Stent Restenosis (PEPPER)

Paclitaxel Releasing Balloon in Patients Presenting With In-Stent Restenosis A Prospective, Multi-centre, Non-randomized Clinical Trial With Follow-up Investigations at 1, 6 and 12 Months

The primary objective of this study is to evaluate the safety and efficacy of the paclitaxel releasing balloon in patients with in-stent restenosis in a coronary artery.

Study Overview

• Status: Completed
• Conditions: In-stent Coronary Artery Restenosis
• Intervention / Treatment: Device: Paclitaxel Releasing Balloon

Detailed Description

All patients are treated with the paclitaxel releasing balloon Pantera Lux. The indication is in-stent restenosis in either bare metal stent (BMS) or drug eluting stent (DES).

Clinical follow up visits at 1, 6 and 12 months. Angiographic follow up visit at 6 months.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Freiburg, Germany, 79106
    • Prof. Dr. Christoph Hehrlein

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:

1. Patient >/= 18 years
2. Written patient informed consent available
3. Patients with stable, unstable or documented silent angina pectoris
4. Patient eligible for percutaneous coronary intervention
5. Patient acceptable candidate for coronary artery bypass surgery
6. Patients with a single restenotic lesion in a previously stented area of a coronary artery (irrelevant whether BMS or DES related)
7. Target reference vessel diameter (visual estimation): 2 - 4 mm
8. Target lesion length (visual estimation): 8 - 28 mm
9. Target lesion stenosis (visual estimation): >/= 50% - < 100%

Exclusion Criteria:

1. Left ventricular ejection fraction of < 30%
2. Visible thrombus in the target vessel visualized by angiography

3. Myocardial infarction (STEMI/NSTEMI) within 72 hours of the intended treatment. Determination of CKMB and/or troponin T or I is required.

   Notes:

   Laboratory assessments to be done within 24 hours prior to intervention. Patients with CKMB and/or troponin T or I > 2 fold the upper limit of normal must not be included in the trial.

4. Patients with planned major surgery within 3 months after planned coronary intervention and/or risk of either acetylsalicylic acid of clopidogrel cessation
5. Lesion length longer than length of available treatment balloon
6. Impaired renal function (serum creatinine > 2.0mg/dl or 177 micro mol/l, determined within 72 hours prior to intervention)
7. Additional coronary lesions (restenotic or de novo) in the same vessel which requires treatment
8. Totally occluded coronary artery (Mehran classification IV and TIMI flow 0)
9. Target lesion located in vessel bifurcation
10. Previous and/or planned brachytherapy of target vessel
11. Target lesion located in left main coronary artery
12. Stroke or TIA < 6 months prior to procedure
13. Patient with signs of a cardiogenic shock
14. Patient under ongoing systemic immunosuppressive therapy with paclitaxel or agents of the -limus group (i.e. sirolimus, tacrolimus, everolimus)
15. Surgeries of any kind within 30 days prior to screening
16. Patient with bleeding diathesis in whom anticoagulation or antiplatelet medication is contraindicated
17. Known allergies to anti-platelet-, anticoagulation therapy, contrast media or paclitaxel
18. Pregnant and/or breast-feeding females or females who intend to become pregnant (pregnancy test required for females of child-bearing potential)
19. Patient with a life expectancy of less than one year
20. Patient currently enrolled in other investigational device or drug trial
21. Patient with known incompliance to medical (antiplatelet, anticoagulation) therapy
22. Patient not able or willing to adhere to follow-up visits including follow-up angiography

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Paclitaxel Releasing Balloon; Percutaneous coronary intervention with paclitaxel releasing balloon	Device: Paclitaxel Releasing Balloon; Percutaneous coronary intervention with paclitaxel releasing balloon; Other Names: Pantera Lux

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In-stent Late Lumen Loss	In-stent is defined as from proximal shoulder to distal shoulder of the dilated Pantera Lux balloon. 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). Offline quantitative coronary angiography (QCA) analysis was performed by an independent core laboratory (Ulrich Dietz, MD, Deutsche Klinik für Diagnostik, Wiesbaden, Germany).	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In-segment Late Lumen Loss	In-segment is defined as from proximal shoulder to distal shoulder of the dilated Pantera Lux balloon plus 5 mm proximal and 5 mm distal. 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). Offline quantitative coronary angiography (QCA) analysis was performed by an independent core laboratory (Ulrich Dietz, MD, Deutsche Klinik für Diagnostik, Wiesbaden, Germany).	6 months
Cumulative Major Adverse Cardiac Events Rate (Composite of Cardiac Death, Non-fatal Myocardial Infarction, Clinically Driven Target Lesion Revascularization, Clinically Driven Target Vessel Revascularization)	All safety endpoint and serious adverse events were adjudicated by an independent clinical events committee. Major Adverse Cardiac Events = MACE Myocardial Infarction = MI Target Lesion Revascularization = TLR Target Vessel Revascularization = TVR	6 months
Cumulative MACE Rate (Composite of Cardiac Death, Non-fatal MI, Clinically Driven TLR, Clinically Driven TVR)	All safety endpoint and serious adverse events were adjudicated by an independent clinical events committee.	12 months
In-stent Diameter Stenosis (%DS)	In-stent is defined as from proximal shoulder to distal shoulder of the dilated Pantera Lux balloon. Diameter stenosis is defined as the difference between reference vessel diameter and minimal lumen diameter divided by reference vessel diameter x100%. Offline quantitative coronary angiography (QCA) analysis was performed by an independent core laboratory (Ulrich Dietz, MD, Deutsche Klinik für Diagnostik, Wiesbaden, Germany).	6 months
In-segment Diameter Stenosis (%DS)	In-segment is defined as from proximal shoulder to distal shoulder of the dilated Pantera Lux balloon plus 5 mm proximal and 5 mm distal. Diameter stenosis is defined as the difference between reference vessel diameter and minimal lumen diameter divided by reference vessel diameter x100%. Offline quantitative coronary angiography (QCA) analysis was performed by an independent core laboratory (Ulrich Dietz, MD, Deutsche Klinik für Diagnostik, Wiesbaden, Germany).	6 months
Binary In-stent Restenosis	In-sent is defined as from proximal shoulder to distal shoulder of the dilated Pantera Lux balloon. Binary restenosis was defined as a ≥ 50% diameter stenosis at follow-up as evaluated by offline quantitative coronary angiography (QCA). Diameter stenosis is defined as the difference between reference vessel diameter and minimal lumen diameter divided by reference vessel diameter x100%. Offline quantitative coronary angiography (QCA) analysis was performed by an independent core laboratory (Ulrich Dietz, MD, Deutsche Klinik für Diagnostik, Wiesbaden, Germany).	6 months
Binary In-segment Restenosis	In-segment is defined as from proximal shoulder to distal shoulder of the dilated Pantera Lux balloon plus 5 mm proximal and 5 mm distal. Binary restenosis was defined as a ≥ 50% diameter stenosis at follow-up as evaluated by offline quantitative coronary angiography (QCA). Diameter stenosis is defined as the difference between reference vessel diameter and minimal lumen diameter divided by reference vessel diameter x100%. Offline quantitative coronary angiography (QCA) analysis was performed by an independent core laboratory (Ulrich Dietz, MD, Deutsche Klinik für Diagnostik, Wiesbaden, Germany).	6 months
Technical Success	Technical success is defined as successful vascular access, completion of the endovascular procedure and immediate morphological success with < 30% residual diameter stenosis assessed by quantitative coronary angiography (QCA). Diameter stenosis is defined as the difference between reference vessel diameter and minimal lumen diameter divided by reference vessel diameter x100%. Offline quantitative coronary angiography (QCA) analysis was performed by an independent core laboratory (Ulrich Dietz, MD, Deutsche Klinik für Diagnostik, Wiesbaden, Germany).	directly after intervention (after finalized treatment)
Device Success	Device success defined as exact deployment of the device as documented by two different projections assessed by quantitative coronary angiography (QCA). Offline quantitative coronary angiography (QCA) analysis was performed by an independent core laboratory (Ulrich Dietz, MD, Deutsche Klinik für Diagnostik, Wiesbaden, Germany).	directly after intervention (after finalized treatment)

Collaborators and Investigators

• Sponsor: Biotronik AG
• Investigators: Principal Investigator: Christoph Hehrlein, MD, University Medical Center, Freiburg i.Br., Germany

Publications and helpful links

General Publications

• Hehrlein C, Dietz U, Kubica J, Jorgensen E, Hoffmann E, Naber C, Lesiak M, Schneider H, Wiemer M, Tolg R, Richardt G. Twelve-month results of a paclitaxel releasing balloon in patients presenting with in-stent restenosis First-in-Man (PEPPER) trial. Cardiovasc Revasc Med. 2012 Sep-Oct;13(5):260-4. doi: 10.1016/j.carrev.2012.06.002. Epub 2012 Aug 4.

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (ACTUAL): December 1, 2010
• Study Completion (ACTUAL): May 1, 2011

Study Registration Dates

• First Submitted: August 13, 2009
• First Submitted That Met QC Criteria: August 17, 2009
• First Posted (ESTIMATE): August 18, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): May 6, 2013
• Last Update Submitted That Met QC Criteria: May 2, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: paclitaxel; drug eluting balloon; in-stent restenosis; BMS-ISR; DES-ISR
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Coronary Disease; Coronary Stenosis; Coronary Restenosis; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: C0902