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

A Multicenter, Randomized Study of the Sirolimus-Eluting Bx VELOCITY® BALLOON Expandable Stent vs. Intravascular Brachytherapy in the Treatment of Patients With In-Stent Restenotic Coronary Artery Lesions

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.

Study Overview

• Status: Completed
• Conditions: In-Stent Restenosis
• Intervention / Treatment: Device: Sirolimus-Eluting Bx Velocity® Balloon Expandable Stent; Procedure: Brachytherapy

• Study Type: Interventional
• Enrollment (Actual): 384
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester

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. 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;

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Cypher Bx Velocity	Device: Sirolimus-Eluting Bx Velocity® Balloon Expandable Stent; Sirolimus-Eluting Bx Velocity® Balloon Expandable Stent
Active Comparator: 2; Brachytherapy	Procedure: Brachytherapy; Brachytherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Target vessel failure (TVF) defined as cardiac death, myocardial infarction, or target vessel revascularization at 9 months post-procedure.	9 months post-procedure.

Secondary Outcome Measures

Outcome Measure	Time Frame
Target lesion revascularization (TLR) at 6 and 9 months post-procedure.	6 and 9 months post-procedure
Target vessel revascularization (TVR) at 6 and 9 months post-procedure.	6 and 9 months post-procedure
Angiographic in-lesion and in-stent binary restenosis (³ 50% diameter stenosis) at 6 months post-procedure (by QCA).	6 months post-procedure
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].	6 months post-procedure
Post-procedure and six-month in-stent and in-lesion minimum lumen diameter (MLD) (by QCA).	Post-procedure and at six-month
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	30 days and 6, 9, and 12-months, and 2, 3, 4, and 5 years post-procedure
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.	post-procedure and six months
Cost associated with the index hospitalization, length of stay, and repeat hospitalizations during the 12 mo post-procedure follow-up.	12 mo post-procedure
Rate of late thrombosis	Throughout study

Collaborators and Investigators

• Sponsor: Cordis Corporation
• Investigators: Principal Investigator: David R. Holmes, Jr., MD, Mayo Clinic - Rochester, Minnesota

Publications and helpful links

General Publications

• Holmes DR Jr, Teirstein P, Satler L, Sketch M, O'Malley J, Popma JJ, Kuntz RE, Fitzgerald PJ, Wang H, Caramanica E, Cohen SA; SISR Investigators. Sirolimus-eluting stents vs vascular brachytherapy for in-stent restenosis within bare-metal stents: the SISR randomized trial. JAMA. 2006 Mar 15;295(11):1264-73. doi: 10.1001/jama.295.11.1264. Epub 2006 Mar 12.
• Holmes DR Jr, Teirstein PS, Satler L, Sketch MH Jr, Popma JJ, Mauri L, Wang HP, Schleckser PA, Cohen SA; SISR Investigators. 3-year follow-up of the SISR (Sirolimus-Eluting Stents Versus Vascular Brachytherapy for In-Stent Restenosis) trial. JACC Cardiovasc Interv. 2008 Aug;1(4):439-48. doi: 10.1016/j.jcin.2008.05.010.

Study record dates

Study Major Dates

• Study Start: February 1, 2003
• Primary Completion (Actual): January 1, 2005
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: September 30, 2005
• First Submitted That Met QC Criteria: September 30, 2005
• First Posted (Estimate): October 4, 2005

Study Record Updates

• Last Update Posted (Estimate): November 19, 2009
• Last Update Submitted That Met QC Criteria: November 17, 2009
• Last Verified: November 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: P02-6313