In-stent Coronary Artery Restenosis
Conditions
Keywords
paclitaxel, in-stent restenosis, BMS-ISR, DES-ISR, drug eluting balloon
Brief summary
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.
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.
Interventions
DEVICEPaclitaxel Releasing Balloon
Percutaneous coronary intervention with paclitaxel releasing balloon
Sponsors
Biotronik AG
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| In-stent Late Lumen Loss | 6 months | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Major Adverse Cardiac Events Rate (Composite of Cardiac Death, Non-fatal Myocardial Infarction, Clinically Driven Target Lesion Revascularization, Clinically Driven Target Vessel Revascularization) | 6 months | 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 |
| Cumulative MACE Rate (Composite of Cardiac Death, Non-fatal MI, Clinically Driven TLR, Clinically Driven TVR) | 12 months | All safety endpoint and serious adverse events were adjudicated by an independent clinical events committee. |
| In-stent Diameter Stenosis (%DS) | 6 months | 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). |
| In-segment Diameter Stenosis (%DS) | 6 months | 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). |
| In-segment Late Lumen Loss | 6 months | 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). |
| Binary In-segment Restenosis | 6 months | 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). |
| Technical Success | directly after intervention (after finalized treatment) | 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). |
| Device Success | directly after intervention (after finalized treatment) | 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). |
| Binary In-stent Restenosis | 6 months | 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). |
Countries
Germany
Participant flow
Recruitment details
From 14 August 2009 to 26 April 2010 a total of 81 patients at 9 heart centres in Europe were enrolled. Last follow-up was completed 09 May 2011.
Pre-assignment details
No group assignment.
Participants by arm
| Arm | Count |
|---|---|
| Paclitaxel Releasing Balloon Patients meeting all inclusion and none of the exclsuion criteria were enrolled and treated with the study device, the Pantera Lux paclitaxel releasing balloon, as per protocol. | 81 |
| Total | 81 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Paclitaxel Releasing Balloon |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 51 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants |
| Age Continuous | 66 years STANDARD_DEVIATION 9.4 |
| Region of Enrollment Denmark | 5 participants |
| Region of Enrollment Germany | 67 participants |
| Region of Enrollment Poland | 9 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 76 |
| serious Total, serious adverse events | 11 / 76 |
Outcome results
Primary
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).
Time frame: 6 months
Population: 2 patients died, 2 patients withdrew consent, 6 patients refused repeat angiography at 6 months follow up, 8 patients could not be analysed by QCA
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paclitaxel Releasing Balloon | In-stent Late Lumen Loss | 0.07 mm | Standard Deviation 0.31 |
Secondary
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).
Time frame: 6 months
Population: 2 patients died, 2 patients withdrew consent, 6 patients refused repeat angiography at 6 months follow up, 8 patients could not be analysed by QCA
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paclitaxel Releasing Balloon | Binary In-segment Restenosis | 1 participants |
Secondary
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).
Time frame: 6 months
Population: 2 patients died, 2 patients withdrew consent, 6 patients refused repeat angiography at 6 months follow up, 8 patients could not be analysed by QCA
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paclitaxel Releasing Balloon | Binary In-stent Restenosis | 2 participants |
Secondary
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.
Time frame: 12 months
Population: 2 patients died, 2 patients withdrew consent, 1 patient lost to follow up
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paclitaxel Releasing Balloon | Cumulative MACE Rate (Composite of Cardiac Death, Non-fatal MI, Clinically Driven TLR, Clinically Driven TVR) | 9 participants |
Secondary
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
Time frame: 6 months
Population: 2 patients died, 2 patients withdrew consent
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paclitaxel Releasing Balloon | Cumulative Major Adverse Cardiac Events Rate (Composite of Cardiac Death, Non-fatal Myocardial Infarction, Clinically Driven Target Lesion Revascularization, Clinically Driven Target Vessel Revascularization) | 5 participants |
Secondary
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).
Time frame: directly after intervention (after finalized treatment)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paclitaxel Releasing Balloon | Device Success | 80 participants |
Secondary
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).
Time frame: 6 months
Population: 2 patients died, 2 patients withdrew consent, 6 patients refused repeat angiography at 6 months follow up, 8 patients could not be analysed by QCA
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paclitaxel Releasing Balloon | In-segment Diameter Stenosis (%DS) | 29.9 percentage of re-narrowing | Standard Deviation 10.6 |
Secondary
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).
Time frame: 6 months
Population: 2 patients died, 2 patients withdrew consent, 6 patients refused repeat angiography at 6 months follow up, 8 patients could not be analysed by QCA
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paclitaxel Releasing Balloon | In-segment Late Lumen Loss | 0.02 mm | Standard Deviation 0.32 |
Secondary
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).
Time frame: 6 months
Population: 2 patients died, 2 patients withdrew consent, 6 patients refused repeat angiography at 6 months follow up, 8 patients could not be analysed by QCA
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paclitaxel Releasing Balloon | In-stent Diameter Stenosis (%DS) | 25.9 percentage of re-narrowing | Standard Deviation 11.7 |
Secondary
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).
Time frame: directly after intervention (after finalized treatment)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paclitaxel Releasing Balloon | Technical Success | 81 participants |