# Presentation: 511804

## FDA Summary

**GuardWire System**
**PercuSurge, Inc.**
**K003992**

## FDA Summary

**FDA Review Team**
**Device Description **
**Nonclinical Evaluation**
**Clinical Evaluation**
**Panel Questions**

## FDA Review Team

**ODE****	****-****	****Suzanne Kaiser**
**	****	****	****	****Paul Chandeysson**
**OSB****	****-****	****Gary Kamer**
**OC****	****-****	****Liliane Brown**

## Device Description

**GuardWire Plus Catheter**
**Export Aspiration Catheter **
**MicroSeal Adapter**
**EZ Flator**
**System Accessories**

## Device Description (cont.)

**GuardWire vs. GuardWire Plus**
**GuardWire Plus Subject of 510(k)**

## Nonclinical Evaluation

***In Vitro *****Testing **
**Biocompatibility Testing**
***In Vivo***** (Animal) Testing**

## Device Malfunctions

**Incidence**
**Affect on MACE**
**Panel Questions**

## Clinical Investigations

**	****Saphenous Vein Graft Angioplasty Free of Emboli Randomized Study (SAFER)****  **

## Clinical Evaluation

**Paul Chandeysson, MD**
**Medical Officer, DCRD**

## Clinical Data

**Prospective, multicentered Randomized Clinical Trial (RCT)**
**Patients needing treatment of a single Saphenous Vein Graft (SVG)**
**Randomized to treatment with GuardWire or without GuardWire (1:1)**

## Primary Response Variable

**Major Adverse Cardiac Events (MACE) at 30 days after the treatment**
**MACE includes death, Q-wave or non-Q-wave myocardial infarction, emergent bypass surgery, or repeat target vessel revascularization.**

## Patient Enrollment

**Roll-in Phase for training operating teams**
**800 patients were to be randomized **
**Interim analyses by the data safety monitoring board after the enrollment of   350 and 550 patients with stopping rules based on 30 day MACE rates**

## Inclusion Criterion Change

- 	After 142 patients had been randomized and treated, the inclusion criterion defining the type of lesions to be treated was changed from: “a maximum of two lesions within a single saphenous vein graft” to:
- 	“one or more lesions within a single saphenous vein graft, located in the proximal segment (5 mm distal to the anastomotic site), mid-body segment and distal segment ( 20 mm proximal to the distal anastomotic site.)**	****	****	****	****	**

## Two Similar RCTs

- 	The change in the inclusion criterion resulted in two similar RCTs with different lesion characteristics and numbers of patients
- _Number of Patients_
-                 GuardWire    Control        Total
- RCT-1          72              70             142
- RCT-2        273             278             551**	****	****	****	**

## Patient Characteristics

- 	A comparison of 18 demographic and clinical characteristics of the patients showed there was no significant difference between the test and control group in either RCT and no significant difference between the two RCTs.

## Lesion Characteristics

- 	A comparison of 15 characteristics of the lesions showed no significant difference between the test and control groups in either of the two RCTs.  The only significant difference between the lesions in RCT-1 and RCT-2 was the percent of calcified lesions.
- _Percent Calcified Lesions_
-              GuardWire    Control
- RCT-1       1.3%           4.0%
- RCT-2      25.4%        23.9%

## Different Treatment Effects

- 	**The treatment effect as measured by the MACE rates was apparently different in the two RCTs.**
_**MACE Rates at 30 Days**_
**	****	****GuardWire****	****	****Control**
**	****RCT-1   9/ 72=12.5%     7/ 70=10.0%**
**	****RCT-2   27/273=9.9%    55/278=19.8%**
**	**
**	****The treatment effect seen in RCT-2 was not apparent in RCT-1.  The primary difference was in the MACE rates of the control groups.**

## Possible Causes of the Different MACE Rates

**Small size of RCT-1**
**Calcification of lesions**
**Other lesion characteristics**

## Panel Questions

## Panel Question 1

**1.****	****Please discuss whether there are any substantial differences in the lesions treated in RCT-1 and RCT-2 that could affect the poolability of the data.**

## Panel Question 2

**	**
**2.****	****Please comment on this difference in control results.  Are there any other methods that should be used to assess interventional risk in a diseased SVG? **

## Panel Question 3

**3.****	****Considering both the planned a priori and realized post hoc interim looks at these data, do you have any recommendations regarding the following questions:**
**Please discuss the Type I error values that should be associated with each planned or realized look.  These values must assure an overall study Type I error of 0.05.  Their values may not only impact the results of hypotheses tests but may also change the widths of the reported confidence intervals.  These changes could influence the evaluation process and the labeling.**
**Please discuss whether the 142 patients enrolled prior to the change in the inclusion criteria should be included in the primary analysis.  If not, which patient cohort should be the primary analysis cohort?**

## Panel Question 4

**	**
**4.****	****Please discuss the clinical importance of the device failure and malfunction events in the evaluation of the safety and effectiveness of the GuardWire System.**

## Panel Question 5

**	**
**5.  ****Based on the data submitted by the applicant please discuss whether the benefits of the distal protection device in this patient population outweigh the risks associated with the use of this device.**

## Panel Question 6

**6a.Based on the data from RCT-1 and RCT-2 as ****	****discussed in question 2, do you recommend that the Percusurge device be labeled for use in all SVG lesions? Please comment on the INDICATIONS FOR USE section (page 2) as to whether it identifies the appropriate patient population for treatment with the device.**
**6b.Please comment on the CONTRAINDICATIONS as  to whether there are conditions under which the device should not be used because the risk of use clearly outweighs any possible benefit.****	**

## Panel Question 6 (cont.)

**6c.Please comment on the WARNINGS and PRECAUTIONS sections as to whether it identifies all potential hazards regarding device use.  **
**6d.Please discuss whether any improvements could be made to the labeling to help minimize the occurrence of device failures and malfunctions as discussed under question 4.**

## Panel Question 6 (cont.)

**6e.Please comment on the remainder of the device labeling as to whether it adequately describes how the device should be used to maximize benefits and minimize adverse events.**
**6f.Do you have any other recommendations regarding the labeling of the device?**

## Panel Question 7

**7a.Please discuss any improvements that could be made to the training program to help minimize the occurrence of device failures and malfunctions as discussed under question 4.**
**7b.Please identify any other important elements that should be contained in a physicians training program for this device.****   **