Swain 23 Oct. 021

Embol-X

Clinical Reviewers

Wolf Sapirstein M.D.

Julie Swain M.D.

(Cardiothoracic Surgery)

Swain 23 Oct. 022

Study Design

• Randomized, multicenter

• Control 644 patients, Filter 645 patients

• Control arm = patients without filter

• Interim data analysis at 50% of patients

Swain 23 Oct. 023

Investigational Plan

• “If the hypothesis tests performed at the interim are statistically significant, indicating emboli capture and equivalent safety, the study will be terminated”

• The study was continued to completion to attempt to show safety superiority (which was not shown)

Swain 23 Oct. 024

Inclusion/Exclusion Criteria

• Elective operations• Isolated CAB or valve• Age >60• Total 24 exclusion criteria

– Neurological deficit – Hx major stroke (as defined by a clinical history of

fixed, focal neurological deficit attributable to stroke) – Redo operations– Renal failure on dialysis

Swain 23 Oct. 025

Neurological Evaluation(Gross Neurologic Testing)

• History, Physical Exam

• NIH Stroke Score

• No neuropsychological testing

Swain 23 Oct. 026

Endpoints

• Efficacy: >75% of filters trap at least one particle

• Composite Primary Safety: 12 items (Not worse than control group with an equivalency delta of 5%)

• Secondary Safety: Aortic Injury (not part of composite safety endpoint)

Swain 23 Oct. 027

Patient Demographics

• No statistical differences in baseline characteristics between treatment and control group

• Treatment group:– 73% male– 91% Caucasian– Average age 71 years

Swain 23 Oct. 028

Types of operations

CABG

AVR

MVR/R

8%6%

84%

Swain 23 Oct. 029

Composite Safety Endpoint(12 clinical events)

• DeathNeurological• Stroke• TIA• Non-metabolic comaRenal• Creatinine >2.0 or increased 50% (non-dialysis)• DialysisGastrointestinal• Bleeding requiring transfusion• Pancreatitis• Cholecystitis• Mesenteric ischemiaCardiac• Q-wave MI• Non Q-wave MILimb threatening periph. embolism

Diminished pulseAltered pallorPain

Swain 23 Oct. 0210

Number of Particles Trapped

0

10

20

30

40

50

60

% filters

0 1-5 6-10 11-20 >20

Maximum number trapped = 25 (38 in roll-in)Total number of particles embolized unknown

Mean 5.6 particles/filter

Swain 23 Oct. 0211

Selected Events

0123456789

10

Death Stroke ARF(dialysis)

Q wave MI AorticInjury

Filter

Control

%patients

*

* P < .001

Swain 23 Oct. 0212

Manipulation-Related Aortic Injury

0

4

8

12

FilterRollIn Filter

Control

% patients

*

* p<0.001 vs control

7/78 42/456

9/454

Swain 23 Oct. 0213

Manipulation-Related Aortic Injury

• Occurred in 9.2% of filter patients (42/456 patients)

• 3 filter patients required aortic repair

• Study protocol follow-up: 30 day or hospital discharge, whichever occurred first (median follow-up 7.0 days)

• Post hoc designed telephone follow-up of 43/49 aortic injury patients (roll in + randomized), 18/49 had > 1 year follow-up

• No apparent training effect

• Not associated with increase in Adverse Events

Swain 23 Oct. 0214

Post-Hoc Data Analysis

• These analyses were not planned prospectively in the investigational plan

• Statistical treatment of post hoc analyses is not straight-forwardNominal p-values do not account for

multiplicityNo way to know how much adjustment should

be applied when judging "significance"

Swain 23 Oct. 0215

Selected Adverse Events(Higgins score >5)

0

2

4

6

8

Death Stroke ARF (dialysis) Q wave MI

Filter

Control

%patients

p = N.S. for all points

4

5

8

6

4

6

5

3

Swain 23 Oct. 0216

Summary

Embol-X Control p value

Trapped at least

one particle

97%

Composite safety

endpoint

17.1% 18.9% n.s.

Individual safety events n.s.

Aortic injuries 9.2% 2.0% <.001

Swain 23 Oct. 0217

Conclusions

The filter traps particles

A correlation with clinical improvement was not shown

Additional concerns were raised by the occurrence of aortic injuries