Sirolimus-Eluting Stent vs. Intravascular Brachytherapy in In-Stent Restenotic Coronary Artery Lesions(SISR)

• Angiographic in-lesion and in-stent binary restenosis (³ 50% diameter stenosis) at 6 months post-procedure (by QCA). [ Time Frame: 6 months post-procedure ] [ Designated as safety issue: Yes ]
• Post-procedure and six-month in-stent and in-lesion percent diameter stenosis (%DS) and late loss at 6 months post-procedure (by QCA) - [analysis at 6 months chosen so that results from the GAMMA Trial can be used]. [ Time Frame: 6 months post-procedure ] [ Designated as safety issue: Yes ]
• Post-procedure and six-month in-stent and in-lesion minimum lumen diameter (MLD) (by QCA). [ Time Frame: Post-procedure and at six-month ] [ Designated as safety issue: Yes ]
• Target lesion revascularization (TLR) at 6 and 9 months post-procedure. [ Time Frame: 6 and 9 months post-procedure ] [ Designated as safety issue: Yes ]
• Target vessel revascularization (TVR) at 6 and 9 months post-procedure. [ Time Frame: 6 and 9 months post-procedure ] [ Designated as safety issue: Yes ]
• Composite of Major Adverse Cardiac Events (MACE) defined as death, myocardial infarction (Q wave and non-Q wave), emergent bypass surgery, or repeat target lesion revascularization at 30 days and 6, 9, and 12-months, and 2, 3, 4, and 5 years post-proce [ Time Frame: 30 days and 6, 9, and 12-months, and 2, 3, 4, and 5 years post-procedure ] [ Designated as safety issue: Yes ]
• Stent lumen and stent obstruction volume by intravascular ultrasound (IVUS) at post-procedure and six months in a subset of patients conducted at 5-7 investigational centers. [ Time Frame: post-procedure and six months ] [ Designated as safety issue: Yes ]
• Cost associated with the index hospitalization, length of stay, and repeat hospitalizations during the 12 mo post-procedure follow-up. [ Time Frame: 12 mo post-procedure ] [ Designated as safety issue: No ]
• Rate of late thrombosis [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

• The following secondary endpoints will be assessed:
• · Angiographic in-lesion and in-stent binary restenosis (³ 50% diameter stenosis) at 6 months post-procedure (by QCA).
• · Post-procedure and six-month in-stent and in-lesion percent diameter stenosis (%DS) and late loss at 6 months post-procedure (by QCA) – [analysis at 6 months chosen so that results from the GAMMA Trial can be used].
• · Post-procedure and six-month in-stent and in-lesion minimum lumen diameter (MLD) (by QCA).
• · Target lesion revascularization (TLR) at 6 and 9 months post-procedure.
• · Target vessel revascularization (TVR) at 6 and 9 months post-procedure.
• · Composite of Major Adverse Cardiac Events (MACE) defined as death, myocardial infarction (Q wave and non-Q wave), emergent bypass surgery, or repeat target lesion revascularization at 30 days and 6, 9, and 12-months, and 2, 3, 4, and 5 years post-proce
• · Rate of late thrombosis.
• · Stent lumen and stent obstruction volume by intravascular ultrasound (IVUS) at post-procedure and six months in a subset of patients conducted at 5-7 investigational centers.

The main objective of this study is to demonstrate the superiority or non-inferiority of the sirolimus-eluting Bx VELOCITY® stent compared to intravascular brachytherapy in patients with in-stent restenotic native coronary artery lesions.

• Device: Sirolimus-Eluting Bx Velocity® Balloon Expandable Stent
  Sirolimus-Eluting Bx Velocity® Balloon Expandable Stent
• Procedure: Brachytherapy
  Brachytherapy

• Experimental: 1
  Cypher Bx Velocity
  Intervention: Device: Sirolimus-Eluting Bx Velocity® Balloon Expandable Stent
• Active Comparator: 2
  Brachytherapy
  Intervention: Procedure: Brachytherapy

Inclusion Criteria:

• 1. The patient has an in-stent restenosis of > 50% (by subjective angiographic determination of the minimal luminal diameter compared to the distal reference diameter) within a native coronary artery which has previously undergone stent placement ( 4 weeks). Lesions must meet ISR Classification I-III.

  2. The patient has a history, signs of, or laboratory studies that suggest coronary ischemia attributable to the target stenosis. The diagnosis of angina pectoris is defined by Canadian Cardiovascular Society Classification (CCS I, II, III, or IV) OR unstable angina pectoris (Braunwald Classification B&C, I-II) OR patients with documented silent ischemia;

  3. The study target lesion must be located in an in-stent restenotic native coronary artery measuring > 2.75mm and 3.5mm in diameter and > 15mm and 40mm in length to allow treatment with a maximum of three 18mm stents. The target lesion must have undergone coronary interventional treatment > 4 weeks previously. Patients with one or more prior percutaneous coronary interventions at the target lesion are acceptable candidates.

  4. The vessel 1cm distal to the target lesion is > 2.5mm in diameter;

  5. Ejection Fraction must be > 40%;

  6. The study target lesion cannot be located in a vessel containing a second lesion requiring treatment at the time of the procedure.

  7. Male or non-pregnant female patients > 18 years of age inclusive. NOTE: Females of child-bearing potential must have a negative pregnancy test (urine or serum) prior to enrollment and must use birth control for 6 months.

Exclusion Criteria:

1. The study target lesion has definite or possible thrombus present by angiographic criteria.
2. The patient has experienced a Q-wave or non-Q-wave myocardial infarction with documented total CK > 2 times normal within the preceding 24 hours and the CK and CK-MB enzymes remain above normal at the time of treatment.
3. Impaired renal function (Serum creatinine > 2.0mg/dl);
4. The patient has unstable angina classified as Braunwald III B or C, or is having peri infarction angina.
5. The left ventricular ejection fraction is < 40%.
6. The target vessel has previously sustained a perforation.
7. Totally occluded vessel (TIMI 0 level);
8. Prior stent within 5mm of target lesion;
9. There is a total occlusion of the restenosed-stent (ISR Classification IV) prior to the interventional procedure.
10. Has an ostial target lesion;
11. Significant (> 50%) in-stent restenoses proximal or distal to the target lesion that might require revascularization or impede runoff;