Randomized Trial Evaluating Slow-Release Formulation TAXUS Paclitaxel-Eluting Coronary Stent in the Treatment of In-Stent Restenosis

Study Overview
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Brief Summary
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The objective of this study is to evaluate the safety and effectiveness of the TAXUS Express2 Paclitaxel-Eluting Coronary Stent System as compared to brachytherapy in patients experiencing in-stent restenosis.

Detailed Description
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Percutaneous approaches to in-stent restenosis (ISR) have included balloon angioplasty alone, rotational atherectomy, cutting balloon angioplasty, directional coronary atherectomy, excimer laser angioplasty, placement of a second stent or any combination thereof, and intra-coronary brachytherapy. Of these, only brachytherapy has been shown to reduce recurrent restenosis after PCI for ISR, - and is now considered the standard of care. Logistical considerations in establishing and maintaining a radiation program have limited the widespread availability of this modality. These considerations include the need for involvement of radiation oncologists, physicists, and safety officers; nuclear licensing requirements; need for increased shielding and safety training; equipment and procedural complexities; as well as increased procedural time and costs. Furthermore, recurrent ISR after brachytherapy may still occur. Stent based drug delivery for the treatment of ISR holds promise as a much simpler, safer and potentially more effective alternative to brachytherapy. This is a prospective, randomized (1:1), open-label, multicenter, safety and efficacy trial for the treatment of in-stent restenosis. The primary objective is to demonstrate a superior or non-inferior 9-month target vessel revascularization (TVR) rate for TAXUS-SR stent compared to intra-coronary brachytherapy (beta source).

Official Title
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A Prospective, Randomized Trial Evaluating Slow-Release Formulation TAXUS Paclitaxel-Eluting Coronary Stent in the Treatment of In-Stent Restenosis

Conditions
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Coronary Restenosis

Intervention / Treatment
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* Device: TAXUS Express2
* Procedure: Brachytherapy (beta source)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cumulative target lesion length is </= 46 mm (visual estimate). Reference vessel diameter (RVD) is >/= 2.5 and </= 3.75 mm (visual estimate) Left ventricular ejection fraction (LVEF) is >/= 25% Exclusion Criteria: Any previous or planned treatment with a non-study anti-restenotic drug-coated or drug-eluting coronary stent in the target vessel. (Note:previous or planned treatment with heparin or phosphorylcholine coated stents is acceptable, as long as, the procedure with the non-study stent meets the protocol defined criteria for non-target lesion interventions.) Previous or planned treatment with intra-coronary brachytherapy (gamma or beta source) in the target vessel Previous external radiotherapy to the heart or target vessel area Known genetic radiation sensitivity disorders (i.e. ataxia-telangiectasia, etc.) Side branch of the target lesion includes ostial narrowing >/= 50% diameter stenosis (DS) and is >/= 2.0 mm diameter Target lesion has been previously treated for ISR with the placement of a second stent(s), which covers >/= 50% of the original stent length (a true stent sandwich) Target vessel is pre-treated with an unapproved device, directional or rotational coronary atherectomy, laser, or transluminal extraction catheter immediately prior to delivery of randomized treatment (stent placement or intra-coronary brachytherapy) Recent myocardial infarction (MI) (symptom onset </= 72 hours prior to randomization) CK-MB >2x the local laboratory's upper limit of normal (ULN) (refers to a measured value on the day of the index procedure as drawn per protocol) Anticipated treatment with warfarin during any period in the 6 months post index procedure Anticipated treatment with paclitaxel, oral rapamycin or colchicine during any period in the 9 months post index procedure Planned use of both the study stent and a non-study stent (i.e., commercial stent) in the treatment of the target lesion

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Device: TAXUS Express2<br>* Paclitaxel-Eluting Coronary Stent System<br>|
| Active Comparator: Arm 2<br> | Procedure: Brachytherapy (beta source)<br>* Brachytherapy (beta source)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Target Vessel Revascularization |  | 9 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of composite major adverse cardiac events (MACE) and the individual components of MACE |  | assessed at discharge, 1, 4 and 9 months post index procedure and annually for 5 years | 
| Stent thrombosis rate |  | 5 Years | 
| Target Vessel Failure (TVF, defined as any ischemia-driven revascularization of the target vessel, MI related to the target vessel, or death related to the target vessel). |  | 5 Years | 
| Clinical procedural success and technical success |  | 5 Years | 
| Binary restenosis rate |  | 5 years | 
| Evaluate outcomes and treatment of recurrent restenosis in the TAXUS stent arm |  | 5 Years | 
| Absolute lesion length |  | 9 Months | 
| Reference Vessel Diameter (RVD) |  | 9 Months | 
| Minimum Lumen Diameter (MLD) |  | 9 Months | 
| Percent diameter stenosis (% DS) |  | 9 Months | 
| Acute gain |  | 9 Months | 
| Late loss |  | 9 Months | 
| Loss index |  | 9 Months | 
| Patterns of recurrent restenosis, including edge effect |  | 9 Months | 
| Coronary aneurysm |  | 9 Months | 
| Identification of potential safety issues. |  | 9 Months | 
| Change in neointimal volume from post procedure to follow-up |  | 9 Months | 
| Change in MLD within the stent or area of brachytherapy |  | 9 Months | 
| Minimum lumen area (MLA) within the stent or area of brachytherapy |  | 9 Months | 
| Lumen, plaque and vessel measurements at the treatment edges (outside of the stent or area of brachytherapy) |  | 9 Months |