MIST I & III StudiesMIST I & III Studies

Andrew J. DowsonDirector Headache Services

King’s College Hospital

London, UK

For the MIST investigators

Within the past 12 months, I or my spouse/partner Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or have had a financial interest/arrangement or affiliation with the organization listed below.affiliation with the organization listed below.

Affiliation/Financial RelationshipAffiliation/Financial Relationship CompanyCompany

Grant/Research Support NMT MedicalGrant/Research Support NMT Medical

Disclosure Statement of Disclosure Statement of Financial InterestFinancial Interest

MIST I InvestigatorsMIST I InvestigatorsCardiologists

J De-Giovanni

D Hildick-Smith

WS Hillis

A Khan

I Malik

L Morrison

M Mullen

P Wilmshurst

Neurologists

A Dowson*

G Elrington

SL Lipscombe

K Muir

S Nightingale

R Peatfield

T Rees

C Wells

DSAEMB

H Sievert**

E Eeckhout**

L Doyal

R Kern

F Baudet

R Taylor

L Missault***

*Study chief Investigator** Chairman of DSAEMB*** Medical monitor

Eligible Migraine PatientsEligible Migraine Patients

Contrast Transthoracic Echocardiogram (cTTE)Contrast Transthoracic Echocardiogram (cTTE)

3 Month Healing Phase3 Month Healing Phase

PFO Closure with STARFlex®PFO Closure with STARFlex® Sham ProcedureSham Procedure

MIST I Trial Design

3 Month Analysis Phase3 Month Analysis Phase

aspirin &clopidogrelaspirin &

clopidogrel

TEE and Randomization Under GATEE and Randomization Under GA

MIST - OutliersMIST - OutliersHistogram of Total Number of Migraine Headache Days per Month

for Each Patient in Analysis Period per Protocol Population

Total Number of Migraine Headache Days per Month

Nu

mb

er o

f P

atie

nts

MIST Study Exploratory AnalysesMIST Study Exploratory Analyses

05

101520253035404550

% R

ed

uct

ion Implant

Shampp<0.027*<0.027*

Total Migraine Headache DaysTotal Migraine Headache Days

*=2 outliers removed

Closure Rate 94%Closure Rate 94%

As reported per protocol by As reported per protocol by implanting cardiologistimplanting cardiologist

MIST IIIMIST III

Interim AnalysisInterim Analysis

Active ArmActive Arm

Additional 18 month f/uAdditional 18 month f/u

MIST III Trial DesignMIST III Trial Design

Followed for 6 months Followed for 6 months

Sham ArmSham Arm

Offered PFO Closure with STARFlex® when unblindedOffered PFO Closure with

STARFlex® when unblinded

Additional 18 month f/uAdditional 18 month f/u

MIST III DemographicsMIST III Demographics

Implant Sham

# enrolled# enrolled 5454 3535

Age (mean)Age (mean) 46.246.2 46.146.1

Sex (% female)Sex (% female) 89%89% 89%89%

Race (% Caucasian)Race (% Caucasian) 98%98% 100%100%

Atrial septal aneurysmAtrial septal aneurysm 31%31% Not knownNot known

MIST III – Headache DaysMIST III – Headache Days

0

1

2

3

4

5

6

7

Baseline 6m 9m 12m 15m 18m

Mean

Median

Time (months)

Hea

dac

he

Day

s

N 52 52 36 36 40 33

MIST III – 50% Responder RateMIST III – 50% Responder Rate

3m 6m 9m 12m 15m 18m

N 52 52 36 36 40 33

MIDAS Total Score MIDAS Total Score

0

10

20

30

40

50

60

Baseline 3m 6m 12m 15m 18m

Mean Median

Time (months)

MID

AS

To

tal

Sco

re

N 48 46 47 30 27 21

Severe 21+Moderate 11-20

Mild or infrequent 6-10Minimal or infrequent 0-5

HIT- 6 Total ScoreHIT- 6 Total Score

45

47

49

51

53

55

57

59

61

63

65

67

69

Baseline Day 90 Day 180 9m 12m 15m 18m

Mean Median

Time (months)

HIT

- 6

To

tal

Sco

re

N 48 46 47 45 29 27 21

≥ 60 – Severe56-59 Substantial

50-55 Some impact< 50 – Little or no impact

MIST III Interim FindingsMIST III Interim Findings

• MIST headache-day reductions hold MIST headache-day reductions hold and improve over time.and improve over time.

• Disability measures improve over time.Disability measures improve over time.

• Encouraging results need to be Encouraging results need to be replicated in current randomized replicated in current randomized controlled trials.controlled trials.