Symbiot III: A Prospective Randomized Trial Evaluating the Symbiot Covered Stent System in Saphenous Vein Grafts

The objective of the Symbiot III Clinical Trial was to evaluate the safety and effectiveness of the Symbiot Covered Stent System in the treatment of symptomatic ischemic saphenous vein bypass graft disease.

Symbiot III was a prospective, multi-center, randomized, controlled trial to evaluate the safety and efficacy of the Symbiot stent compared to bare metal stents in the treatment of symptomatic ischemic saphenous vein graft disease. Randomization was stratified by the intended use of intravenous glycoprotein IIb/IIIa inhibitors and by the intended use of approved distal protection to ensure approximate balance between study treatments within each of the strata. The primary outcome variable for the study was target lesion percent diameter stenosis at 8 months post-implant.

• Device: Covered Stent System
  Self-expanding, polytetrafluoroethylene(PTFE)-covered, stent system
  Other Name: Symbiot Covered Stent System
• Device: Bare metal stent
  Any commercially available bare metal stent for coronary indication

• Experimental: 1
  Symbiot Covered Stent System
  Intervention: Device: Covered Stent System
• Active Comparator: 2
  Commercially available bare metal stent
  Intervention: Device: Bare metal stent

General Inclusion Criteria:

1. Patient >=18 years old
2. Patients is eligible for percutaneous coronary intervention and stenting
3. Patient is an acceptable candidate for repeat CABG
4. CPK must be within ULN on the day of the procedure

5. Patient must meet one of the following requirements:

   • treatment of one or two de novo or restenotic lesions in a single SVG
   • treatment of both a native coronary artery and the target graft in a single procedure, provided that the native artery is treated prior to randomization of the target lesion(s) and did not result in MACE or TIMI flow <3
6. Patients (or their legal representative) understands the nature of the procedure and study requirements and provides written informed consent before any study specific tests or procedures are performed
7. Patient is willing to comply with specified follow-up evaluations at the specified times and locations
8. Patient has angina pectoris (CCS 1, 2, 3, or 4) or coronary ischemia documented by a positive functional ischemia study
9. Patient has no child bearing potential or has a negative pregnancy test within 7 days prior to treatment

Angiographic Inclusion Criteria:

1. Target lesion(s) are located within a single SVG
2. Reference vessel >=3.5 mm and <=5.5mm in diameter at the stent deployment site
3. Cumulative target lesion length is <=41mm
4. Target lesion(s) randomized to treatment with the study device must be completely covered by 1 or 2 stents (maximum allowable aggregate stent length in target vessel of 51 mm)
5. Target lesion stenosis >=50% and <100%

General Exclusion Criteria:

1. Patient is currently enrolled in another IRB-approved trial that has not reached the primary endpoint visit or is still in the active treatment phase
2. Patient has been previously enrolled in any Symbiot Trial
3. Patient has documented left ventricular ejection fraction of <30% within 30 days of enrollment
4. Patient has had a myocardial infarction within 48 hours prior to trial procedure and/or CK-MB >2X the ULN

5. Patient has had, or will have, a planned additional interventional procedure to any coronary vessel (coronary artery or saphenous vein graft) that does not meet the following criteria:

   If the staged procedure is chosen for non-study percutaneous intervention to any non-target vessel:

   • 30 days or more prior to the index procedure is allowed
   • Between 24 hours and 30 days prior to the index procedure is allowed provided that no major adverse cardiac events resulted from the staged non-study procedure
   • Within 24 hours prior to the index procedure not allowed
   • Within 30 days after the index procedure is not allowed
   • 30 days or more after the index procedure is allowed
6. The lesion to be treated is within 10 mm of any anastomosis
7. Patient has life expectancy of less than 1 year due to other medical conditions
8. The lesion(s) to be treated requires debulking prior to stent placement
9. Patient has a pre-existing condition for which aspirin is contraindicated
10. Patient has a pre-existing condition for which clopidogrel and ticlopidine are contraindicated
11. Patient has a known hypersensitivity to nickel

Angiographic Exclusion Criteria:

1. Target vessel is a left main artery-equivalent graft
2. Target vessel is an internal mammary artery graft
3. Target lesion(s) have any intraluminal thrombus present with TIMI flow <3
4. Target vessel has excessive tortuousity unsuitable for delivery and deployment of Symbiot
5. Target lesion(s) is/are within a previous stented segment
6. Target or non-target vessel requires pre-treatment with an adjunctive non-balloon device (e.g., DCA, TEC, Rotablator or laser) prior to stent placement during the stent placement procedure
7. Treatment with non-approved distal protection systems
8. Target lesion(s) involve either the ostium or distal anastomosis
9. Target lesion(s) are at or immediately distal to a >45 degree bend in the vessel
10. Target vessel is a degenerated SVG (diffuse segments of disease >41 mm in length with stenosis, ectasia and probable thrombus)
11. Untreated lesions are present proximal or distal to the target site which may compromise inflow or outflow of the treatment site after stent deployment