# Presentation: 175674

## Panel Questions-Clinical Trial Design

**1.****	****Can the data from the investigator-sponsor studies be considered in the evaluation of high risk stenting given the differences in trial conduct for the high-risk investigator-sponsor registries?**

**Notes:**
As demonstrated by the results included in Table 1 of the START Clinical Report (page 5), the incidence of the primary endpoint, target vessel failure, was significantly lower at 8 months for the treatment arm (SR-90) compared to the placebo.  The incidence of target vessel revascularization, target lesion revascularization, and major cardiac adverse events (MACE) were also significantly lower over the 8-month follow-up period for the treatment arm compared to the placebo.  No incidents of stent thrombosis were detected in the treatment arm, and the frequency of total occlusions was comparable between the treatment and placebo arms.

Question 3:  Please discuss whether you believe the probable clinical benefit of the radiation treatment outweighs the probable risks of death, myocardial infarction, late total occlusion, and late stent thrombosis posed by the device in the intended patient population.

## Panel Questions-Clinical Trial Design

**2.****	****How does the large enrollment in the registry CAS arm affect interpretation of results?**

## Panel Questions-Clinical Trial Design

**3.****	****How does premature termination of the pivotal randomized study affect conclusions derived from this study?**

## 4.	Please discuss how data from previous carotid treatment trials (NASCET, ACAS) can be used to analyze the current peri-operative/30-day data set with regard to safety.

**4.****	****Please discuss how data from previous carotid treatment trials (NASCET, ACAS) can be used to analyze the current peri-operative/30-day data set with regard to safety.**
** **

**Notes:**
As demonstrated by the results included in Table 1 of the START Clinical Report (page 5), the incidence of the primary endpoint, target vessel failure, was significantly lower at 8 months for the treatment arm (SR-90) compared to the placebo.  The incidence of target vessel revascularization, target lesion revascularization, and major cardiac adverse events (MACE) were also significantly lower over the 8-month follow-up period for the treatment arm compared to the placebo.  No incidents of stent thrombosis were detected in the treatment arm, and the frequency of total occlusions was comparable between the treatment and placebo arms.

Question 3:  Please discuss whether you believe the probable clinical benefit of the radiation treatment outweighs the probable risks of death, myocardial infarction, late total occlusion, and late stent thrombosis posed by the device in the intended patient population.

## Panel Questions-Safety and Effectiveness

**5.****	****There were multiple ways for higher risk patients to be entered into the SAPPHIRE trial.  Please discuss the impact of these various patient subgroups on ability to generalize safety and effectiveness results.**

## Panel Questions-Safety and Effectiveness

**6.****	****Effectiveness of stroke prophylaxis has historically required 2 to 5 years monitoring, with safety outcomes generally assessable within the lesser period of 1 year.   Please discuss whether chronic data presented for the OTW configuration in the SAPPHIRE trial provide evidence of sustained effectiveness of CAS in preventing stroke in patients at high risk for CEA.**

## Panel Questions-Safety and Effectiveness

**7.****	****Is it appropriate for the sponsor to employ OPCs developed from NASCET and ACAS outcomes to assess outcomes for both symptomatic and asymptomatic patients in the SAPPHIRE Trial?**** ****Or should the ACAS rates from the asymptomatic trial be used for comparison?**

## Panel Questions-Safety and Effectiveness

**8.****	****The ACAS and NASCET studies did not include myocardial infarction (MI) as an endpoint.  The SAPPHIRE trial included MI as a component of MAE.  The distribution of non-Q-wave MI’s are provided under Tab 8 (Addendum) of the Panel Pack.  Please comment on the sponsor’s choice of this composite endpoint.**

## Panel Questions-Safety and Effectiveness

**9.****	****The indications for carotid artery stenting in the registry arm were largely dictated by hazards of surgical exposure.  The ability to deploy a stent should not be affected by these criteria.  Are outcomes achieved in this registry, i.e., 10% stroke and TIA at 30 days and additional 16% at one year acceptable?**

## Panel Questions-Safety and Effectiveness

**10.****	****Please comment on whether the incidence of ipsilateral stroke is acceptable.**

## Panel Questions-Safety and Effectiveness

**12.****	****The various studies employed a total of only four size 5mm stents.  Does the Panel believe that there are adequate safety and effectiveness information for this size?**

## Panel Questions-Safety and Effectiveness

**13.****	****Has the totality of data presented in the carotid stent PMA shown reasonable assurance of safety and effectiveness for the OTW configuration?  If not, what niche indications have been shown to be safe and effective for carotid stenting?**

## Panel Questions-Labeling

**14.****	****Are the indications and contraindications for the OTW configuration clear and supported by the SAPPHIRE study findings?  If not, please identify the indication you believe is supported by the sponsor’s data.  Specifically, is stenting of asymptomatic patients supported?  Should any criteria stipulating when stenting of asymptomatic patients is appropriate be included in the labeling?**

**Notes:**
As demonstrated by the results included in Table 1 of the START Clinical Report (page 5), the incidence of the primary endpoint, target vessel failure, was significantly lower at 8 months for the treatment arm (SR-90) compared to the placebo.  The incidence of target vessel revascularization, target lesion revascularization, and major cardiac adverse events (MACE) were also significantly lower over the 8-month follow-up period for the treatment arm compared to the placebo.  No incidents of stent thrombosis were detected in the treatment arm, and the frequency of total occlusions was comparable between the treatment and placebo arms.

Question 3:  Please discuss whether you believe the probable clinical benefit of the radiation treatment outweighs the probable risks of death, myocardial infarction, late total occlusion, and late stent thrombosis posed by the device in the intended patient population.

## Panel Questions-Labeling

**15.****	****Patients with complex atherosclerotic disease of the aorta or highly tortuous carotid arteries are not optimal candidates for carotid stenting.  Please comment on the adequacy of the OTW configuration labeling with regard to patients with these anatomic characteristics.  If there are candidates that are not optimal that should be added, please also identify them.**

## Panel Questions-Labeling

**16.****	****Should any other warnings and/or precautions be stipulated in the labeling for the OTW configuration in addition to those found in the proposed labeling?**

## Panel Questions-Post-market Study Design

**17.****	****Please comment on whether the sponsor’s post approval study plan is adequate.  If not, what additional information do you believe should be collected post-approval?  Specifically, do you recommend that an independent neurologist make the neurological assessments at each follow-up (currently only proposed for discharge and 30 days)?**

## Panel Questions-Training

**18.****	****Please comment on whether the sponsor’s training plan is adequate.  If not, what additional requirements do you believe should be added to the training program for the OTW configuration? **