# Presentation: 663525

## Cardica Proximal Anastomosis System510k  0304034Wolf Sapirstein MPH, FACSClinical ReviewFDA/CDRH/ODE

- FDA Clinical Presentation

## FDA Recommended StudyDesign for CABG AnastomosisDevices

- Observational  Study
- 510K clearance
- Effectiveness:
- LCB for 95% CI, 80% angiographic patency at 6-months
- One year clinical evaluation with Stress-ECG.
- Safety:
- Procedure adverse events. Adverse events to 1 year
- MACE (Mortality; TVR; Myocardial infarction)
- Control:
- Sutured anastomosis
- Historical
- FitzGibbon

- FDA Clinical Presentation

**Notes:**
1-2cmlife 
10 year criteria but device being used on that vesel type

## PAS-Port Study 1

- Enrolled 		55 patients
- Failed Use		8 patients
- Implanted		47 patients; 54 devices
- Not Evaluated		2 withdrew; 1 discontinued
- Angiograms		39 in 44 patients; 42 grafts		  			82.9% cases implanted
- Patent grafts		36 of 42 grafts
- 				85.7%, LCB 73.7%
- Not followed		2 Deaths; 3 discontinued
- Stress-ECG 		36 of 42 patients/1 positive
- 				78.2% living

- FDA Clinical Presentation

**Notes:**
Degradation of 20%

## PAS-Port Study 1Effectiveness

- Observed Patency (6-Month Angio.)
- 36 of 42 implants in 39 patients
- 		85.7%, LCB 73.7%
- Imputed Patency
- 43 of 50 implants in 47 implanted patients
- 			86.0%, LCB 75.3%
- Intention to treat (Imputed)
- CABG procedures patent in 50 of 60 grafts  	83.3%, LCB 71.4%
- Device grafts patent in 43 of 60 grafts
- 		71.1%, LCB 59.0%

- FDA Clinical Presentation

**Notes:**
Failed as treated 
Attempts at mining for large rsample sizes and ItT

## PAS-Port Study 1Safety

- MACE (12/24 months 42 patients)
- Deaths				2 (4.7%)
- Myocardial Infarction		1 (2.3%)
- Graft occlusion			6 (14%)
- K-M estimate of rate at 24 Months:
- 		20.2% (UCB 30.1%) of 47 patients per protocol
- 		17.5% (UCB 26.2%) of 55 intent to treat patients
- Non-Device Adverse events
- Myocardial Ischemia 3; Infarction 1; Revasc 4
- Hospital event rates similar to historical data bases

- FDA Clinical Presentation

**Notes:**
Non-devie AE ?

## PAS-Port StudyCohort 2

- Enrolled			54 patients
- 	(133 Consented and 118 enrolled in parent study)
- PAS-Port Intended  	63 devices
- Failed Implant 		2   patients
- Implanted			52 patients, 59 devices
- Hospital Death 		2   patients
- Discontinued		4   patients
- Six-month Angio.		38 of 46 patients
- 45 of 47 grafts patent
- One-year Follow-up:	46 patients
- One-year Stress-ECG:	42 patients
- Negative Stress test 	38 patients

- FDA Clinical Presentation

**Notes:**
Retrospective 

## PAS-Port Study  Cohort 2Effectiveness

- Observed Patency (6-month angio)
- 45 of 47 grafts patent in 38 patients
- 95.7%, LCB 87.2%
- Imputed Patency (All device grafts)
- 55 of 59  grafts
- 93.0%, LCB 85%
- Imputed Patency (Intent to treat)
- 57 of 63  CABG procedures (all intended)
- 90.5%, LCB 80%

- FDA Clinical Presentation

**Notes:**
Some problem in following assessment grafts vs patients

## PAS-Port Study Cohort 2Safety 

- MACE
- Death				4 (7.6%)
- Myocardial Infarction		0
- Graft Occlusion/stenosis	5 (9.6%)
- K-M estimated rates at 1 year:
- Per Protocol (50 patients) 12.7% (UCB 20.7%)
- Intent to Treat (54 patients) 15.5% (UCB 23.6%)
-  Adverse Events
- Myocardial Ischemia		6 (11.5%)
- Revascularization		9 (17.3%)
- Graft stenosis		          11 (21.1%)

- FDA Clinical Presentation

**Notes:**
? Of data analysis

## PAS-PortCombined Study 1 and Cohort 2  

- Enrollment		109   patients
- Failed Implants		12	patients
- Implants		97	patients
- Hospital deaths		2	patients
- Lost follow-up		7	patients
- 6-month Angio		77    	patients (90 grafts)
- Angio patent		81 	grafts (89 grafts)
- Imputed  Patency		17	patients
- MSCT/MRI patent 			10	patients
- Stress-ECG negative 			5  	patients
- CCS			2 	patients
- 12/24 Month Stress-ECG		78 	patients
-  Ischemic			5	patients

- FDA Clinical Presentation

## PAS-PortCombined Study 1 and Cohort 2 Effectiveness 

- Observed Patency for 99 patients
- 81 of 89 grafts in 77 patients
- 91%, LCB 84%
- Imputed Patency Device for 107 patients
- 98 of 109 grafts
- 89.9%, LCB  83.8%
- Imputed Patency Intent to Treat (grafts)
- 107 patent CABG grafts in 123 grafts
- 87%, LCB

- FDA Clinical Presentation

**Notes:**
CL are for 90% CI not 95%

## PAS-Port Patency Imputation 

- Study 1:
- Implants (47 patients)
- Angio: 	39 patients evaluated
- 		36 (85.7%) of 42 grafts patent
- 		72% of all 50 implants
- MRI     	5 patients
- Stress ECG	2 patients
- Died	1 patient
- Suture Conversions (8 patients)
- Stress ECG 	7 patients
- CCS	1 patient

- FDA Clinical Presentation

**Notes:**
Basis is for imputation

## PAS-PortImputed Patency 

- Cohort 2
- Implants  (50 patients)
- Angio 		38 patients (73.7 % all implants)
- 				45 grafts of 47 implants (95.7%)
- MSCT		5 patients
- Stress-ECG	3 patients
- CCS		2 patients
- Suture Conversions (2 patients)
- CCS		2 patients

- FDA Clinical Presentation

##  Study Design Limitations 

- Modification to study protocols after study initiation
- Cohort 2 sample stratified  from a study enrolled under a different protocol for a different CABG device
- Problems with Pooling of Study 1 and Cohort 2:
- Inclusion criteria different
- Cohort 2 retrospective enrollment
- Cohort 2 employed 2 experimental devices
- Baseline variability
- Instrument modification

- FDA Clinical Presentation

**Notes:**
Address failure reported European and Japanese  (31 cases) !0 failures in Syudy 1

##  Safety and Effectiveness Concerns

- Angiography
- Study 1: 39 of 47 patients implanted (82.9%)
- Cohort 2: 38 of 52 patients implanted (73%)
- Imputation of Patency (Combined groups)
- 20 of 97 implanted patients (20%)
- 26 of 109 intent to treat (23.8%)
- Imputation Criteria (Combine groups)
- MRI/MSCT		10
- Stress ECG		11
- CCS			5

- FDA Clinical Presentation

##   Safety and Effectiveness Concerns (cont’d)

- Stress ECG
- 36 of 45 survivors  1 Ischemia
- 39 of 48 survivors  4 Ischemia
- Thrombo-Embolism
- Two events
- Stenosis/Occlusion
- 11 Stenoses
- 9 Ischemia
- 1 Myocardial infarction
- MACE
- PAS-Port  CABG supplied <= 22% Left Ventricle

- FDA Clinical Presentation

**Notes:**

Problem in determining the relation of ischemia listed as adverse events and results of Stress ECG Ischemia treated as nob-device
T-e concevably device source
st

## PAS-Port Anastomosis System Study Conclusions

- Study 1 did not meet the pre-specified effectiveness hypothesis.
- The poolability of Study 1 and Cohort 2 is problematic.
- Angiographic follow-up of patients is incomplete.  The Sponsor relied on imputations with non-invasive technologies to assess patency.
- The attribution of several adverse events as “non-device related” is questionable.

- FDA Clinical Presentation