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S3 MonitorforHomeHaemodialysisTechnical Overview

(potentiële)belangenverstrengeling Geen/Ziehieronder

Voorbijeenkomstmogelijkrelevanterelatiesmetbedrijven Eucept Homecare

• Sponsoringofonderzoeksgeld• Honorariumofandere(financiële)

vergoeding• Aandeelhouder• Andererelatie,namelijk…

• Geen• Employee

• Geen• Geen

Disclosurebelangenspreker

What is Physidia?

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Physidia founded,Angers(FR),11/2010

CEMark,2013

Medical InnovationAward,2016

InternationalDevelopment &Clinical Evidence,

2017

1st patienttreated,Clinical study,

2013

…acontinuous evolution

Ourvalues

• TherapeuticInnovation• AtrueServiceCulture• Expertise

Clinicalbenefitsofdailyhaemodialysis

Clinicalbenefits:ureareduction

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• Ureareductionbyhaemodialysis cannotreplicatenormalkidneyfunction[1]

• BUT

• Increasingdialysisfrequencyreducesintradialyticchangesandlowerstheaverageconcentration[2]

ComparisonofestimatedGFRvaluesforHDwithnormalkidneyfunction[1]

Clinicalbenefits:cardiacprotection

• Fluid over-load leadstoincreased left ventricular mass(LVM)&is associated withmortality &cardivascularmorbidity [3]

• TheFrequent Hemodialysis Trial(FHT)daily trialdemonstrated a13.1%reduction inLVM

• Thegreatest reduction occuredinthose who already had leftventricular hypertrophy

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Clinicalbenefits:weightandbloodpressurecontrol

• Reductions inintradialytic weight gainandbloodpressurewere also evident inthose ondailydialysis [3]AdjustedMeanChangesinNetVolumeRemoval,BloodPressureandPre-dialysisPhosphorusover12months

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Dailyhaemodialysis – Clinical benefits – Summary

Cardio-vascularsystem

Hypertension[4,5]

Antihypertensivetreatment[4]

Leftventricularhypertrophy[6,7]

Phospho-calcicmetabolism

Phosphorus[8,9]

Phosphatebindersdose[8]

PTH[8]

Nutritionalstatus

Nutrientandmineralintake[11]

Predialysis serumalbumin[12,13]

Qualityoflife

Qualityoflife(SF36)[10]

Recoverytimeafterdialysissession[10]

Generalhealth[10]

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Clinicalbenefitsofconvectivetherapies

Convectivetherapies

On-linehaemodiafiltration:

Variousstudieshavereportedthefollowing:

• Betterhaemodynamic stabilityduringdialysis• Betterphosphateclearance• Bettermiddlemoleculeclearance• Decreasedinflammatorymarkers• IncreasedEPOresponsiveness

ComparedwithconventionalHD

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Improvedclearanceofmiddleandhighmolecularweight

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T.Cornelisstudy[15]– AdaptedschemaRandomizedstudyon13patientsinHDorpost-dilutionHDF(15l)withFx80dialyzer(Fresenius)showingthesignificantimpactofconvectiononeliminationoflargemolecularweightmolecules

Meert study[16]Crossoverstudyon14patientsinHDandHDFmodes(postdilutionat31lofconvection)withtwodialyzertypes(DiaPES HF800– whitebarsandElisio 170H– greybars)showingimprovedeliminationwithconvectivemodes,dependingonmembranechoice.

Cystatin C(13,3kDa) Myoglobin (17,6kDa)

10

30

50

70

90

Urée(60Da) Créatinine(113Da)

β2microglobuline(11,8kDa)

FGF23(32kDa)

Redu

ctionrate%

Reductionrate%

HD HDF

Convectivedialysis(HDF)improvesclearanceofuremictoxinswithincreasedeffectonmiddleorhighmolecularmassmolecules

Simplicity- Security- Sterility

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S3 MonitorforHomeHaemodialysis

Designed fordaily dialysisDesigned forconvectivetherapy

Designed foreasy patientuse

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S3 Innovations• Patenteddisposabledialysatecircuitfor

accurateUFcontrol• Steriledialysisfluid• IRmeasurementofdialysatetemperature• Patentedlinearbloodpumpforeasylining• ConvectivetherapyusingSeCoHD system• Tabletbaseduserinterface• Patientprescriptioncard• Treatmentdataemailedbacktoclinicusing

Wifi• BluetoothconnectedBPcuffwithnohose• Controlofpatientleakagecurrentusing

dedicatedisolationtransformer• Easilyportableduetosmallfootprint,

weightandnorequirementformainswater

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S3 monitor– Patientcard

• Individualizedpatientcardwiththemedicalprescription

• Securedprescription:Thepatientcardholdsallprescriptiondata:Thepatientcanonlychange:– Fluidremoval(withinlimits)– Bloodpump speed(withinlimits)– Dialysatetemperature(withinlimits).

• Truemobility

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Dialysatecircuit• Theflowisgeneratedbyapplyingairpressureandvacuumtopairsoffluid

filledpouches(notbalancechamber)• Thepouchessitinsealedchambers• Thefillingandemptyingcanbeadjustedindependently• Thisallowsforconvectionthroughthedialysermembrane,SeCoHD

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Disposable dialysate circuit

Uf control

Dialysate flowgenerator(150to200ml/min)

Finalheating

S3 monitor– Dialysate module

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• Flowiscontrolledbymeasuringpressuredropacrosscapillarytubes• Pressureisproportionaltoflow

Inletflowrate

Outletflowrate

Dialysatebags

Drain

Steriledialysisfluid• Providedin5litrebags• BicarbonateorLactate• Bicarbonatesuppliedon2compartmentbag• S3monitorensuressealhasbeenbrokenbetweencompartments

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Advantages:• Nocostlyinstallations• Noneedtoconnecttomainswater• Noneedtomonitorqualityofwateror

dialysisfluid• SeCoHD reinfusionfluidissterile• Nodialysateinducedinflammation• RemovesuncertaintyofROwaterquality

allowingconvectivetherapiesathome• Alwaysthesamequality,evenwhen

travelling

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Technical presentation - Tray Dialyzers

• FreechoiceofanyHighFluxdialyseraccordingtopatientclinicalneedsandprecripstionreducingtheriskofanaphylacticreaction.

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Linearbloodpump

• ThelinearbloodpumpisanuniquemodedevelopedbyPhysidia• Simplicityofinstallationofthebloodline• Maximumefficiency• Occlusioncontrolofthebloodlinepumpsegment

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Bloodcircuit

• Anydialysercanbeused• Allpressureportsarehousedinone

module

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Convectivetreatment,SeCoHD• The1st HHDmachinedesignedforconvectivetherapy• SeCoHD:SelfConvectiveHD• Usesthe‘push-pull’technique[17]• Alternatephasesofpushingsteriledialysateintotheblood(backfiltration)• Thenultrafiltrating theexcessfluid• Backfiltrationreducesblindingofthedialyserpores,maintainingclearance

[17]

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Clampclosed,fluidentersblood

Clampisopen,excessfluidleavesblood

S3 monitor– Ultrafiltrationcontrol

• ControlofultrafiltrationwiththepatentedPhysidiamodule– Highprecisioncontrolofdialysateflowrates

• TechnicalinnovationallowsperformingSeCoHDtherapy

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0 2,5s 5s 7,5s 10s

5s 5s

OPEN

ReinfusionSeCoHD ofPhysidiaS3monitor

• Valvetimingandflowcanbeadjustedtoachieveoptimumconvectiveresults

• Convectivevolumesof0to9litrespersession

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Retrospective datawith PhysidiaS3using reinfusion SeCoHD

• 134 patients – 215 sessions (during training period)• Sex: male 74%

0

5

10

15

20

25

30

≤30 30-40 40-50 50-60 60-70 70-80 80-90

%patients

age (years)

Agedistribution

0

5

10

15

20

25

<40 40-50 50-60 60-70 70-80 80-90 90-100 100-110

110-120 >120

poidskg

Weight distribution%

Residual kidney function

- 43%

+ 57%

Datatobepublishedbyend2019

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Treatment dataPhysidiaS3

average min max

Frequency(x/week) 5,9 5 6

Sessionduration(min) 124 120 180

Bloodflowrate(ml/min) 285 250 350

Dialysatflowrate(ml/min) 181 180 200

Convectionvolume 3040 1400 6000

Datatobepublishedbyend201928

Performancesregarding urea removal – Kt/V

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00,51

1,52

2,53

3,54

4,5

0 50 100 150 200 250

SdtK

t/V

Sdt Kt/V(N=215)

0102030405060708090100

<1,8 >1,8 & <2,0 >2,0

%

SdtKt/V

Sdt Kt/Vdistribution(N=215)

Sd Kt/V:2,6+/- 0,5

Sdt Kt/V=168x(1−exp[−eKt/V])/t/[(1−exp[−eKt/V])/(eKt/V)+168/(Nxt)−1],PredictingTreatmentDoseforNovelTherapiesUsingUreaStandardKt/V,J.KLeypoldtetal,SeminarsinDialysis,Vol17,No2(March–April)2004;pp.142–145KDOQI2015,Guideline3,Measurementofdialysis;ureakinetics,p58

Datatobepublishedbyend2019

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Ultrafiltration rate

0

10

20

30

40

50

60

<10 >10 & <13 >13

%

Average ultrafiltrationml/kg/h

UFrate- distribution(N=215)

Average UFrate:8,5ml/kg/h

Datatobepublishedbyend2019

References

1. Consequences of Frequent Hemodialysis: Comparison to Conventional Hemodialysis and Transplantation. John B. Stokes, Trans Am Clin ClimatolAssoc. 2011; 122: 124-136 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116337/

2. Principesetmodalitésd’applicationdel’hémodialyseautraitementdel’insuffisancerénalechronique,B.Canaud,Néphrologie&Thérapeutique;2009;5,218—238

3. DeterminantsofLeftVentricularMassinPatientsonHemodialysis:theFrequentHemodialysis Network(FHN)Trials,ChristopherTChadetal,CircCardiovascImaging.2012March1;5(2):251–261.doi:10.1161/CIRCIMAGING.111.969923.https://www.ncbi.nlm.nih.gov/pubmed/22360996

4. Volumecontrolandbloodpressuremanagementinpatientsundergoingquotidianhemodialysis.G.Nesrallah etal,Am.J.KidneyDis. 2003,Jul;42(1Suppl):13-7.

5. EffectofFrequentorExtendedHemodialysis onCardiovascularParameters:AMeta-analysisP.Susantitaphong etal,JKidneyDis.2012,May;59(5):689–699https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3395217/pdf/nihms361205.pdf

6. In-Center Hemodialysis SixTimesperWeekversusThreeTimesperWeek,G.M.Chertow etal,NEngl JMed2010;363:2287-300https://www.nejm.org/doi/pdf/10.1056/NEJMoa1001593

7. DeterminantsofLeftVentricularMassinPatientsonHemodialysis:theFrequentHemodialysis Network(FHN)Trials,C.T.Chanetal,Circ CardiovascImaging.2012,March1;5(2):251–261https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328963/pdf/nihms366195.pdf

8. Theroleofdailydialysisinthecontrolofhyperphosphatemia,G.Stevenetal,KidneyInternational,2005,Vol.67,Supplement95,pp.S28–S32https://www.kidney-international.org/article/S0085-2538(15)50804-1/pdf

9. Shortdailyhemodialysis isassociatedwithlowerplasmaFGF23levelswhencomparedwithconventionalhemodialysis,J.Zaritsky etal,Nephrol DialTransplant.2014,29:437–441https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3910340/pdf/gft382.pdf

10. Patientsreceivingfrequenthemodialysis havebetterhealth-relatedqualityoflifecomparedtopatientsreceivingconventionalhemodialysis,A.X.Garg etal,KidneyInt.2017,91,746–754https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333984/pdf/nihms844166.pdf

11. Shortdailyhemodialysis rapidlyimprovesnutritionalstatusinhemodialysis patients,R.Galland etal,KidneyInternational,Vol.60(2001),pp.1555–1560https://www.kidney-international.org/article/S0085-2538(15)48026-3/pdf

12. Clinicalandbiochemicalcorrelatesofstarting“daily”hemodialysis,J.D.Woodsetaal,KidneyInternational,Vol.55(1999),pp.2467–2476https://www.kidney-international.org/article/S0085-2538(15)46210-6/pdf

13. Lowfluxdialysatedailyhomehemodialysis:Aresultforthe62firstFrenchandBelgianpatients,A.Benabed etal,Néphrologie &Thérapeutique,13,(2017),18-25http://www.theradial.com/wp-content/uploads/2017/02/011_Benabed-A-Hemodialyse-quotidienne-a-bas-debit-de-dialysat-a-domicile-Nephrol-Ther-2016.pdf

14. Mortalityandcardiovasculareventsinonlinehaemodiafiltration (OL-HDF)comparedwithhigh-fluxdialysis:resultsfromtheTurkishOL-HDFStudy,Erkac Oketal,NDT,Volume28,Issue1,1st January2013,Pages192-202http://ndt.oxfordjournals.org/content/28/1/192.long

15. Engineeringperspectiveontheevolution ofpush/pull-based dialysis treatments,K.Lee,ExpertRev.Med.Devices ,2013;10(5),611–62016. Whithergoest Kt/V?FRANKA.GOTCHetal,KidneyInternational,2000,Vol.58,Suppl.76,pp.S-3–S-18https://www.kidney-

international.org/article/S0085-2538(15)47396-X/pdf17. AcuteHemodynamicResponseandUremicToxinRemovalinConventionalandExtendedHemodialysis andHemodiafiltration:ARandomized

CrossoverStudy,T.Cornelisetal,AmJKidneyDis.2014;64(2):247-25618. Comparisonofremovalcapacityoftwoconsecutivegenerationsofhigh-fluxdialyzersduringdifferenttreatmentmodalities,N,Meert,Nephrol Dial

Transplant,2011;26:2624–2630https://academic.oup.com/ndt/article/26/8/2624/1916177

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