You are invited to join a major new health research study ... · Chronic kidney disease (CKD) is a...

You are invited to join a major new

health research study

This study is testing a treatment which may help

prevent people with kidney disease from needing dialysis

and we need your help

EMPA-KIDNEY - Quick Summary

• Youare invitedto joinan importanthealthresearchstudycalledEMPA-KIDNEY. Its longer name is The Study of Heart and Kidney Protection with Empagliflozin

• Itisentirelyuptoyouifyoutakepartornot

• EMPA-KIDNEY is testing whether taking a medication calledempagliflozinlowerstheriskofworseningkidneydiseaseorheartdiseaseinpatientswithkidneydisease

• Empagliflozin was originally developed to treat people withdiabetes.Inalargeclinicaltrial,empagliflozinreducedthenumberofdeathsfromheartdiseaseinpeoplewhoalreadyhadbothheartdiseaseandtype2diabetes

• Thesameclinicaltrialsuggestedthatthismedicationcouldreducethedevelopmentorworseningofkidneydiseaseinthesepatients

• Because of the way empagliflozin works on the kidney there isgoodreasontobelieveitcouldbenefitpeoplewhethertheyhavediabetes or not. Scientists based at Oxford University want tofindoutwhethertakinganempagliflozinpillonceadaypreventsworseningofkidneydiseaseordeathfromheartdiseaseinpeoplewithkidneydisease

• If you agree to take part, youwill be joining about 5,000 othervolunteers

• Half of the people will get an empagliflozin pill to take once adayand theotherhalfwill get adummy inactivepill (knownasplacebo).Whichtreatmentyoureceive isdecidedbychanceandyouwillnotknowwhichtreatmentyouaregiven

• Joiningthestudyinvolvesattending3clinicappointmentsinthefirst6monthsandthenanappointmentonceevery6months.Ateachappointmentatrainedresearcher(usuallyaresearchnurse)willasksomequestionsaboutyourhealthandgiveyouasupplyofstudypills

• Because kidney disease is identified and tracked by blood andurine tests, at each appointment youwill be asked toprovide abloodandoccasionallyaurinesample(evenifyoustoptakingyourstudypills)

• Youareaskedtostayinthestudyforabout3-4years–itneedstobethislongtomakesurethisstudyisadefinitivetestofthispillonkidneydiseasewhichoftentakesseveralyearstoprogress

• Wewould like to also usemedical and civil registration records(e.g.thosemaintainedbyNHSDigitalandtheUKRenalRegistry)tofollowyourprogress

• If you join the study, your GP will be informed and your usualmedicalcarewillnotbeaffectedbytakingpart

• TheUniversityofOxfordarerunningthestudy.StudypillsandagranttorunthestudyhavebeenprovidedbyBoehringerIngelheimInternationalGmbH(thedrugcompanywhomakeempagliflozin)

• If you’d like to findoutmore, please read the rest of this leafletcarefully

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Kidney disease is common and linked with heart diseaseChronickidneydisease(CKD)isacommoncondition,affectingabout10%-15%ofthepopulation.Itisdiagnosedandmonitoredbymeansofbloodandurinetests.

CKD is caused by many different things, including increasing age.Diabetes, high blood pressure, inflammation in the kidney andinheriteddiseasesarethemostcommonintheUK.

It isknownthatpeoplewithkidneydiseasearebothat riskof theirkidneyproblemworseninganddevelopingheartproblems.

New treatments for kidney disease and heart disease are neededTwenty years ago, a group ofmedicationswhich block a biologicalsystem, called the renin-angiotensin system (RAS), were shown toprotectthekidneyandtheheart.Becauseoftheseclinicaltrials,thesemedicationsarenowwidelyused(andyoumaybetakingone:theirnamesendin‘–pril’or‘–sartan’).Thesesimpletreatmentshavemeantsomepeoplehavenotneededtostartdialysisandhavesavedlives.

However, despite taking RAS blockers, many people with kidneyproblemscontinuetodevelopworseningoftheirkidneydiseaseand/or heart problems. Scientists are searching for new treatments toreducetheremainingriskofkidneyandheartproblemsinpeoplewithkidneydisease.

There is now a new medication called empagliflozin which wasoriginallydevelopedtotreathighbloodsugarinpeoplewithdiabetes,buthas recentlybeen shown tohavebeneficial effectsonboth theheartandkidney.

What is the treatment being tested?Empagliflozincausesbloodsugar(equivalentto10teaspoonsaday)topassintotheurine.Itlikelyalsoincreasestheamountofsalt(sodium)

passingintotheurine.Thisresultsin amodest fall in bodyweightandbloodpressure.

Importantly, a large clinical trialhas shown that empagliflozinreduces the number of deathsfromheartdiseaseinpeoplewhoalready have both heart disease

andtype2diabetes.Becauseoftheseresults,empagliflozinisusedinselectedpatientswithdiabetesaroundtheworld.

The same study suggested empagliflozin might reduce kidneyproblems.Fromthewaywethinkthepillswork,thereisgoodreasontobelievethisnewmedicationcouldbenefitpeoplewhohavekidneydisease,whethertheyhavediabetesornot.

What is the key question the study will answer?EMPA-KIDNEY is a research study coordinated by the University ofOxford.

Thescientists inOxfordwanttofindoutwhethertakingasinglepillof empagliflozineverydaypreventsworseningof kidneydiseaseordeathsfromheartdiseaseinpeoplewhohavekidneydisease.

Why me?Yourdoctorhasreviewedexistingbloodandurinetestresultswhichshow some evidence that you have had protein in your urine or

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reducedkidneyfunctioninthepast.Youareprobablyalreadyawareofthis,butyoumaynotbe,anditisalsopossiblethattheproteininyoururineorreducedkidneyfunctionisnolongerpresent.Youhave thereforebeen invitedto a study appointment to testyour blood and urine again,andtodiscusstakingpartinthestudy.

The scientists need a rangeof people to join the study,including those with only earlysigns of kidney disease risk aswellaspeoplewhohavealreadyseenakidneydoctor.

Youdonothavetohavediabetestotakepart,infactthestudyneedslotsofpeoplewithandwithoutdiabetestojoin.

Do I need to take part?No,youdonothavetotakepartinthisstudy.Itisentirelyyourdecision.Itisimportanttobeawarethatifyoujointhisstudy,itwillnotaffectanydecisionsaboutothermedical treatmentyoumightneedorbereceivingfromyourowndoctors.

Ifyoudodecidetocometothefirststudyappointmentyouwillbegivenanopportunitytoaskquestionsaboutthestudy.Oncewehaverechecked your blood and urine tests, we will also check with thehospitaldoctor leadingthetrial inyourhospital that theythinkyouareappropriatetojointhestudy.WewillalsotellyourGPthatyouwishtotakepart.

Byjoiningthisstudy,youwillbecomepartofoureffortstosavethelivesofpeoplewithkidneyproblemsandhopefullyreducetheneedforkidneydialysisinyearstocome.

Travel expensesThestudycanpayyouback forall reasonablecosts for travelling toyourstudyappointments(e.g.carparkingandpetrolorothertransportcosts).Pleasemakesureyouaskattheclinic.

Otherwise taking part in the study is voluntary and you will notreceivepaymentforyourparticipation(i.e.youaredonatingyourtime,informationaboutyourhealth,andsamplesofyourbloodandurine).

Who decides what treatment I get?Halfthepeopletakingpartinthisstudywillgettheempagliflozinpillandhalfwillgetthedummyinactivepill (knownasplacebo).Whichtreatment yougetwill bedecidedby the computerby chance (liketossingacoin).Thisiscalledrandomization.

You,andyourdoctors,willnotknowwhichtreatmentyouaregivenandthestudystaffwillnotknoweither.Thisensuresthestudygivesresultswhicharereliableandtrustworthy.

Are there any alternative treatments?During the studyyoushouldcontinue to takeanyother treatmentsyou may have been givento treat your kidneys.Indeed, your local doctorswillbeaskedtoensuretheycontinuetotreatyourothermedicalproblemsaccordingto guidance produced byexpertsatalocal,nationalorinternationallevel.

Note that if you are alreadytakingempagliflozin(oranymedicationwiththenameendingin“–gliflozin”),youwillnotbeabletojointhisstudy.

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‘Kidney disease is often a slowly progressive condition, so the study

needs to be 3-4 years long to definitively answer the study question and have a

worldwide impact’

What will I have to do?ForEMPA-KIDNEYtobeabletogivereliableresults,itisimportantthatpeoplestayinthestudyandtaketheirstudypilleverydayforabout3-4years,whereverpossible.

Thestudyneedstobethislongsoitisadefinitivetestoftheeffectsofthepillsonkidneydiseasewhichcantakeyearstoprogress.Theresultsofthestudycouldhaveamajorimpactonhowkidneypatientsaroundtheworldaretreated.

By joining the study,weare askingyou to attend the study clinic 3timesinthefirst6months,andthenattendevery6monthsafterthat.

Ateachstudyappointment,atrainedresearcher(usuallyanurse)willaskyouaboutyourhealthandgiveyouanewsupplyofstudypills.Youwillthenhaveabloodsampletakentomonitoryourkidneysandothereffectsofthestudypills.

At a small number of visits,wewill also ask you to provide a urinesample.

Withyourpermission,wewouldalsoliketostoreleftoverbloodandurineforfuturescientificresearch,includingtestsonyourgenes.Thispartofthestudyisoptional,soyoucanstillparticipateinthestudyifyoudonotwantyourleftoverbloodandurinestoredlong-term.

What happens at the first appointment? At your first studyappointment (called yourScreening Visit), with youragreement, a trained studynursewillcheckyourpreviousblood and urine test resultsandthenexplainthestudytoyou. You will have plenty oftimetoaskquestions.

YouwillthenbeaskedtosignaConsentFormifyouagreetotakepart.

Thestudynursewillthenasksomemoredetailsaboutyourmedicalhistory and current medication. They will also take a fresh bloodsample(about1teaspoonful)andcollectaurinesampletobesenttothelocallaboratoryfortesting.

If you are willing and able to take part in EMPA-KIDNEY, the studyresearchnursewillgiveyouasupplyofpillstotakefor2-3monthstoseeiftakingextrapillseverydayisacceptabletoyou.

TheresearchteamwillwritetoandinformyourGPtoletthemknowthatyouareplanningtojointhestudy.

Thisfirstappointmentisthelongestappointmentandcouldtakeuptoanhourtocomplete.

What happens at the second appointment?2-3monthslater,youwillhaveyoursecondappointment(calledyourRandomizationVisit).Atthisappointmentwewillcheckhowyougotontakingthestudypills.Youwillalsobeaskedifyouremainwillingtocommittothestudyforaround3-4years.

Ifyouarehappytojoin,astudynursewillperformashortinterview,collectanotherbloodsample(about6teaspoonsthistime),askyoutoprovideaurinesample,andgiveyouyournextsetofstudypills.

Thisappointmentshouldonlytake30-45minutestocomplete.

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What happens at the other appointments? Yournextappointment(calledaFollow-upVisit)willbe2monthslater.Afterthatappointment,thestudyresearchnursewillseeyou4monthslaterandthenevery6months.

AteachFollow-upVisit, thestudynursewillaskyouaboutanynewmedical problems since your last appointment, give you the nextsupplyofstudypillsandtakeabloodsample(between3-6teaspoonseachtime)andpossiblyaurinesample.

EachFollow-upVisit isdesignedto ideallytake lessthan30minutes(although the time needed to collect blood samples and dispensestudypillscanvaryfromhospitaltohospital).

FollowingyourlaststudyFollow-upVisit,youwillstopthestudypills.About4weeks later,youwillbeaskedtoprovideonefurtherbloodtest(about1teaspoonful)andaurinesample.

What if I don’t want to carry on with the study? Wehopeyouwillbeabletocontinuetotakethestudypillsforthefullcourseofthestudy.

For the study to produce reliable results, it is necessary both forparticipantstoremembertotaketheirstudypillsasbesttheycan,andforthestudyteamtocollectcompleteinformationaboutthehealthofasmanyparticipantsaspossible.

Yourparticipationisvoluntary.Itremainsyourrighttodecideyouno

‘It is important people in the study take their

pills and come to appointments for as

long as possible’

longerwishto,orarenolongerableto,participateinanyaspectofthestudyatanytime.Alldataaswellasbloodandurinesamplesalreadycollectedfromyouuntilthetimeofdiscontinuationwillbekeptandusedasdescribedbelow.

Ifyouwithdraw,yourusualrightsasanNHSpatientwillnotbeaffectedinanyway.

If youare asked to stopyour studypillsby adoctor, or you choosetostopthemyourself,itwouldbeveryhelpfulifyouwouldallowthestudyteamtostayintouch.Tomakesurethestudyproducesreliableresultswewouldalsoneed,whereverpossible,tocontinuetocollectbloodsamplesatthestudyclinicforthefulltrialduration(3-4years).

Youmaydecidethatyounolongerwishtocometothestudyclinic.Whatwouldhappeninthiscaseisdescribedinmoredetailbelowinthesectionentitled“Whataremydataprotectionrights?”

Blood and urine samplesThebloodsamplesyouprovidewillbeusedtomeasurethingssuchaskidney,liver,heartfunction,andlevelsofbloodsugarandsaltsinyourbody.Thestudyteamwanttomeasurethesethingstoassesstheeffectsofthestudypills.

The urine samples will bemeasuredforproteinmarkersofkidneydiseaseanddamage.

Some of these tests are notroutinely performed by allhospitals,sosomeofthebloodandurinewillbetransportedtoOxford.ThisiswhystudybloodandurinesampleswillneedtobetakenatthestudyappointmentsratherthanatyourGP’ssurgery.

Thestudyresearchnursewillalsoaskyouifyouwouldallowleftover


bloodandurinesamples,togetherwithyourhealthdatacollectedinthisstudy,tobestoredlong-termtohelpinvestigateothereffectsofempagliflozinandotherfutureresearch(seebelow).

Leftoverbloodandurinesamplesarethosewhichhavealreadybeencollected for the purposes of the study, and would be discardedotherwise.Thereisnoadditionalhealthrisktoyou.Youhavethechoicewhetherornotyouwouldliketoparticipateinthisoptionalpartofthestudy.Ifyoudecidethatyoudonotwanttogivepermission,youcanstilltakepartinthemainpartofthestudy.

How much blood will be taken?Theamountofbloodwillvaryatdifferenttimesduringthestudybutwillusuallybebetween3and6teaspoonsofbloodeachtime.

Stored samples and future researchDoctorsalreadyknowaboutsomeofthecausesofkidneydiseaseandheartdisease.Scientistsalsothinkthatotherfactorsmightplayapart,butthereislimitedunderstandingofhowtheywork.

Inparticular,wehave limitedknowledgeabout theeffectofgenes/DNA on the risks of kidney disease, heart disease, strokes, diabetesanda rangeofotherhealthproblemsthatmightbe linkedto thesediseases. These include diseases that your doctormight refer to asmetabolic,cardiovascular,infectiousormalignantdiseases.

Ifwehaveyourpermissiontokeepyoursamples,thenintheyearstocomewemightbeabletomakenew scientific discoveries usingboth the information collectedin the study and by defrostingand analysing your samples(including testing someor all ofyourgenes/DNA).

Withyourconsent,theblood/urinesampleswillbestoredinafreezeroverseenbytheUniversityofOxfordforuptothirty(30)yearsafterthestudyiscompleted,andwillthenbedestroyed.

Allyourbloodandurinesampleswillbestoredwithauniquenumber,whichmeans you cannot be directly identified from them (i.e. theyare“de-identified”fromyournameandotherwrittenpersonaldetailsaboutyou).Pleasenotethatmuch likefingerprints, it is theoreticallypossibletoidentify someone if your samplesaregeneticallyanalyzedor if yoursamplesareputtogetherwithotherdataaboutyou.Butthechancesofsuccessful re-identificationbysomeonewithoutpermissiontodosoareverylowbecauseweimplementadequateorganizationalandsecuritymeasurestoprotectyourdata.

For this future research to happenwemay need to share your“de-identified”sampleswithlaboratoriesoutsideOxfordwhichcanperformspecializedtests.SamplesmayalsobesenttoBoehringerIngelheim1toprocess, togetherwith informationcollected in the study, for theresearchpurposesdescribedabove.

Resultsfromthisresearchmayalsobesharedwithhealthregulators.

Please note that neither you nor your doctors will be given anyinformationfromtheanalysisofbloodandurinesamples, includingany details of your genes/DNA. In particular, having these samplesstored and tested will not affect your ability to get medical or lifeinsurance.

What are the benefits of taking part in this study? Youmaybehelpingyourself,but it isexpectedthatthe informationfromthisstudymayhelpdoctorsandscientiststoimprovetreatment

1Whenwe say Boehringer Ingelheim, in this case wemean it to also include BoehringerIngelheim Group of Companies, who may work with other public or commercial privatepartnerships.


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ParticipantInformationLeaflet(UK)V1.324-SEP-2018Participant Information Leaflet (UK) V1.3 24-SEP-2018

forpeoplewhohavekidneydisease.Ifempagliflozinisshowntohavebenefits,resultsfromthisstudymayhelptopreventdeathsfromheartdiseaseandtheneedfordialysisortransplantationaroundtheworld.

Pleasenotethatyouaredonatingyourtime,informationandblood/urinesamples,forwhichwearegrateful,butyouoryourrelativeswillnotbeable to receiveanyfinancialbenefits fromanydiscoveriesorproducts developed using the results from this study or any futureresearchusingyourhealthinformationanddata.

Are there any risks?Mosttreatmentshavesideeffects,whichsomepeoplemayexperience,andothersmaynot.

EMPA-KIDNEYistestingempagliflozin,whichhasalreadybeentestedinover8,000people.Amongthesepeople,ithasbeengenerallywell-tolerated.Itnowhasalicencefromhealthregulatorsforuseinsometypesofpeoplewhoalreadyhavetype2diabetes.

Nevertheless you may experience some symptoms when takingempagliflozinwhichcomefromthewaythedrugworksinthebody.For example, empagliflozin causes increase salt andwater loss intotheurineandsomepeoplereportnoticinganeedtopassurinemoreoften.Somehavereportedsymptomssuggestiveofdehydration,suchas increased levels of thirst or feeling faint. Itmay be necessary tochangesomeofyourotherpillstocompensate.Suchsymptoms(andothercommonsymptoms)mayalsohappenifyouareontheinactivepill(placebo),astheyarecommoninpeoplebeingtreatedforakidneyproblem or diabetes, and people who are older (e.g. over 75 yearsofage).Suchgroupsofpeoplemaygenerallyexperiencemoresideeffectsthanothergroupsofpeople,buttheymayalsohavemoretogainfromanybeneficialeffectsoftreatments.

Largetrialsinpeoplewithtype2diabeteshavesuggestedempagliflozinmay reduce the risk of sudden and substantial decreases in kidneyfunction (knownasacutekidney injury).Nevertheless, somepeople

takingempagliflozinhaveexperiencedacutekidney injury.Youmaywant to get advice from your doctor as to when or whether youshouldtemporarilydiscontinuestudytreatmentifyouareunwellandcannotdrinkasmuchasusual,andparticularly ifyouarebecomingdehydratedfromvomitingordiarrhea.Asalways,youshouldcontactyourdoctorwhenyoufeelunwell.

Empagliflozin also works by increasing sugar in the urine. This canoccasionallycausepainonpassingurineand/orincreasethechanceofaurineorgenitaltract infection, likethrush.Confirmedinfectionsareusuallyeasilytreatedwithacourseofantibioticsorantifungalpills.If such treatment iseverneeded,yourGPor local study teamcouldhelp diagnose and treat you. In very rare circumstances a bacterialinfectioncouldspreadtotheareaaroundtheanusandgenitals.Suchinfections can be sufficiently serious to require surgical removal ofthedamagedtissueandcanbelife-threatening.Pleasecontactyourdoctorimmediatelyifyoudevelopanysymptomsofpain,tenderness,rednessorswellingofthisarea.

Low blood sugar may also occur in people with diabetes who arealreadytakinginsulinorcertaindiabetespills(likegliclazide).Commonlow blood sugar symptoms include: sweating, shakiness, hunger,restlessness, slurredspeech,andconfusion.A sugarydrinknormallyreversestheproblem.


For people with diabetes, there is a risk of a condition calledketoacidosis.Ifyouhavehadketoacidosisinthelast5yearsyoucannotjointhetrial.Ketonesbuildupifthereistoolittleinsulininthebody,asituationwhichalsoleadstopersistentlyhighlevelsofbloodsugar.Whentakingempagliflozin,ketoacidosiscandevelopwithoutbloodsugar levels being particularly high. The symptoms of ketoacidosisare non-specific, including feeling or being sick, tummy ache andshortnessofbreath.Othersmaynoticethesmellofpeardropsornailvarnishonyourbreath.Ketoacidosisistreatedwithincreasedinsulinandfluidintake.Ketoacidosiscansometimesbelife-threatening(ifnotappropriately treated)andmayneedhospital treatmentwithadripand insulinmay be needed.There is extra information available onketones in a separate information leaflet for thoseparticipantswithdiabetes.

Aswithallmedicines,somepeoplecandevelopanallergicreaction,includingitchyskinoraskinrash.Veryrarely,somepeoplemayrequireimmediate treatment in a hospital or emergency room for swellingaroundthemouthandthroatcausingdifficultyinbreathing.

Yourdoctormayalsonoticethatyourkidneyfunctionslightlydecreasesonstartingempagliflozin.Thismaybetransientandmaynotbeabadthingasitmaybeasignoftheprotectiveeffectofempagliflozin(orperhapsjustnaturalchangesinyourkidneyfunction).Theymayalsonoticea slight increase in theconcentrationsof cholesterol and redbloodcellsinyourblood.

Throughout the study, the research teamwill carefullymonitor youandyourbloodtestsforpossiblesideeffects.Somesideeffectsmaynecessitatestudypillstobestoppedtemporarilyorpermanently.

The study research nurse will keep you up to date with any new

importantinformationwelearnaboutthepills.

Ifyoudoexperienceunexpectedsymptomsandwanttoaskquestions,youcancontactyourlocalstudyresearchnurse,oranEMPA-KIDNEYstudydoctorbasedinOxford,onFreefone08081644060(available24hoursaday,7daysaweek).

What are the other possible disadvantages of taking part?Although empagliflozin does not appear to cross the placenta, it ispossibleempagliflozincouldaffectanunbornchild.Womenwhoarepregnant,plantogetpregnantorarebreast-feedingcannotjointhestudy.Womenwhocouldbecomepregnantmustagreetousehighlyeffectivecontraceptionthroughoutthetrialandforaweekaftertheendofthestudy(typesofcontraceptionwhichareconsideredhighlyeffectivearelistedinthefootnotebelow2).

Ifyoubecomepregnantduringthetrial(orwishtodoso),youshouldstop taking your study pills and tell the local study nurse or studydoctorpromptlysoappropriateactioncanbetaken.Ifyouhaveprivatemedicalinsuranceorrequiretravelinsurance,yourpolicymaybeaffectedbyjoiningthestudy,sopleasecheckwithyourinsuranceprovider.

What will happen at the end of the main part of the study?The results will be published in health or scientific journals, onwebsites (includingwww.ClinicalTrials.gov) andwill be discussed atmajorconferences.Otherswilllearnfromtheresults,whichwehopewill show thatmore lives can be saved by using empagliflozin. Noindividualparticipantwillbeidentifiedinanyreportorpublication.

2 Highly effective methods of contraception include implants, injections, combined oralcontraceptive pills (started at least 3months before joining the trial), intrauterine devices(often known as a coil), vasectomised partner, or true and complete abstinence (i.e. notcalendarortemperaturemethods).


WewilltryourbesttoinformparticipantsandtheirGPsofthestudyresults, andany relatedpublicity.Wewill use studynewsletters andvideosonthestudy’swebsitetoinformpeopleaboutwhatthestudyshows.

Yourcontributiontothestudycouldbeevenmorevaluableifwehaveyourpermissiontogetinformationaboutyourhealthafteryourverylaststudyappointment.Thiswaywecanlearnaboutanylonger-termhealtheffectsofthestudypills.Thismightincludeaquestionnaireorphonecallonceayear.Also,thestudyscientistscancontinuetogetinformationaboutyourhealth,suchasdetailsfromyourdoctors,NHSDigital(orothercentralNHSregistry)andtheUKRenalRegistry.

Who is running the study?EMPA-KIDNEYwillbecoordinatedbyscientistsfromOxfordUniversity’sClinicalTrialServiceUnit(CTSU).

CTSU isoneof theworld’s leading centres for this typeof research.SpecificallythestudyisledbyDrsRichardHaynes,WilliamHerringtonand David Preiss. They will be supported by many kidney doctors,diabetesdoctorsandotherspecialitydoctorsandnursesaroundtheUK,aswellasotherpartsoftheworld,tomakethisstudypossible.

The EMPA-KIDNEY team has permission from a national ethicscommittee to do the study in the UK (Oxford C Research EthicsCommittee,Ref.No.18/SC/0155).Thiscommitteehascheckedthatthehealthquestionbeingaskedisimportantenoughtowarrantastudy,andthatthestudyisbeingcarriedoutinanindependent,honestandprofessionalmanner.

Anindependentcommitteeofexpertsalsowatchesoverthestudyandkeepsaneyeontheprogressofthestudyandsafetyoftheparticipants.Thiscommitteecouldstopthestudyearlyiftherewasimportantnewinformationfromthis,orother,studieswhichaffectedwhetherEMPA-KIDNEYshouldcontinue.

StudiessuchasEMPA-KIDNEYtakeaverylargeamountofcollaborativeeffort frommany hundreds of research staff around the world and

can be costly to run. The studyis sponsored by BoehringerIngelheim, which is alsoproviding the study pills and agranttotheUniversityofOxford.Those running the study at theUniversityofOxfordalso receivesupport from the UK MedicalResearch Council and BritishHeartFoundationtoruntrials.

How will information be collected about me?Duringyourparticipationinthestudy,youwillprovidepersonaldataabout yourself, such as information on yourmedical condition andmedicalhistory,tothestudynursesatyourstudyvisits(andrelevantbloodandurinetestresultsheldatyourhospital).ThesedatawillbeenteredintoacomputersystemmanagedbytheUniversityofOxfordandstoredsecurely.

TheUniversityofOxford is aworld-leader indeveloping systems toensure that information is stored safely for studies such as EMPA-KIDNEY.Onlystaffwithappropriatetrainingandpermissioncanaccessthiscomputersystem.

Inaddition,thecoordinatingcentreinOxfordwillaskforinformationabout your health from your doctors, registries (e.g. the UK RenalRegistry), andNHSDigital (or other centralNHSbodies).The EMPA-KIDNEYteamwouldsendyourname,dateofbirth,NHSnumber(orCHInumberinScotland)andpostcodetoNHSDigital(orothercentralNHSbody)whocan linkthis informationto individualparticipants in thestudy.ForparticipantslivinginEnglandandWales,NHSDigitalprovidesinformationaboutanycanceronbehalfofPublicHealthEngland.NHSDigital and other central NHS bodies together provide informationaboutadmissions tohospital (calledHospitalEpisodeStatistics)and


developmentof cancer. Inaddition, theyprovide informationaboutpeoplewho have died.This informationmaymean the study teamdoes not make contact and cause any distress to relatives, as thisinformation includesdateandcauseofdeathsuppliedonbehalfoftheOfficeforNationalStatistics.SimilarinformationwillberequestedfromtherelevantbodiesforparticipantslivinginScotland.

What will happen to information about me?Thereareanincreasingnumberofdataprotectionregulationsthatarerequiredtobefollowed.Theselawsrequireustodiscloseyourrightsandhowwewilluseyourdata.

Thetwopartiesinvolvedinthistrial(theUniversityofOxford,whosefulllegalnameis“TheChancellor,MastersandScholarsoftheUniversityof Oxford”, and Boehringer Ingelheim International GmbH will beresponsiblefordecidinghowanypersonaldatacollectedduringthisstudyareprocessedandwillensuredataprotectionlawsarefollowed(i.e. theywill be the“data controllers”). Bothparties areboundbyadutyofconfidentiality.

WheretheUniversityofOxfordisusingyourinformationforresearchpurposes, it will only process personal data as necessary for theperformanceofsuchresearchbeingcarriedoutinthepublicinterest.This is known under data protection law as our “legal basis” forprocessingpersonaldata.

In this study personal data that directly identifies you such as yourname,address,ordateofbirth(so-calledpersonalidentifiers)canbeaccessedby the EMPA-KIDNEYdoctors andnurseswhoare runningthe study at your local hospital. Health regulators (such as the UKMedicineandHealthcareRegulatoryAgencyandU.S.FoodandDrugAdministration) and auditors from Boehringer Ingelheim could alsoaccessthesedataiftheyweretoevervisityourlocalhospitaltocheckthatthestudyisbeingcarriedoutproperly.Thesepeoplearealsoallboundbyadutyofconfidentiality.

Duringthestudy,amemberoftheOxfordUniversityorotherEMPA-KIDNEY staff may ask your permission to be present during yourclinicappointment.Thishelpsusensurestudyproceduresarebeingfollowed.

In theUK,yourname,dateofbirth,NHSnumber (orCHInumber inScotland)andpostcodewillalsobestoredsecurelybytheUniversityofOxfordtolinkyouwithdataheldbyNHSDigital(orothercentralNHSbodiesortheUKrenalregistry)–seesectionabove.OxfordUniversitywill not send these personal identifiers to anyone else (includingBoehringerIngelheim).

Tohelpkeepyourinformationconfidential,informationrecordedaboutyouinthisstudyaswellasanysamplescollectedare“de-identified”.De-identified means that your health information and blood/urinesamplesare labelledwithuniquenumbers linked insideacomputerandnotbyyourname.

As already explained above, it is really very hard for anyone to re-identify you after de-identification as we use special measures toprotectdata,butitremainstheoreticallypossible.

The“de-identified”datainthisstudyaretobeusedforthefollowingpurposes:analysisofthestudyresults,tohelplearnmoreabouthowempagliflozin and other “gliflozins” work in the body, to do futureresearch,towritescientificarticlesonkidneydiseasesandassociatedhealthproblems,andtohelpdesignandconductfuturestudies.

Oxfordwill provide Boehringer Ingelheimwith a copy of the studydatabase containing de-identified data only. It may be necessaryfor copies of the de-identified database to be shared with healthregulators and ethics committees, and itmay be sharedwith otherbonafideresearchers.

3IncludingBoehringerIngelheimGroupofCompanies

ParticipantInformationLeaflet(UK)V1.324-SEP-2018Participant Information Leaflet (UK) V1.3 24-SEP-2018 Page 21Page 20

Oxford and Boehringer Ingelheim3 may process and combine datafromthisstudywithdatafromothersources(alwaysusingappropriatesafeguards)andmaycarryouttheseactivitiesaloneorincollaborationwithpublicorcommercialprivatepartnerships(i.e.thirdparties)intheareasofresearchdescribedabove.

Someoftheabovementionedpartieswhoreceivedatawillbelocatedoutside theUK. Ifany foreigncountry towhichde-identifieddata istransferred does not have equivalent data protection standards tothoserequired in theUK,appropriatesafeguardswillbeadoptedtoprotectandmaintaintheconfidentialityofyourdataandblood/urinesamples (including using standard data protection clauses adoptedby the European Commission, where relevant). If you require anyinformation about these safeguards, you may contact us (see dataprotectionofficeremailaddressbelow).

TheUniversityofOxfordwillsafelykeepthestudydataandBoehringerIngelheimwillsafelykeepthecopyofthede-identifieddatabaseforatleast25yearsaftertheendofthestudy,andperhapslongerifrequiredbythelaworotherresearchneeds.

What are my data protection rights?Ifyoustoptakingthestudypillsanddonotwishtohavefurtherbloodsamples to be collected at your study clinic (see section“What if Idon’twanttocarryonwiththestudy”),itwouldbeveryhelpfulifwecouldkeep in touchbyphone.However,youcanalsodecline tobecontactedagain.Inthiscase,wewouldliketocontinuetofollowhow

youaregettingonbycontactingyourlocaldoctororthroughnationalregistriesorotherpublicallyavailablesourcesofdata.

Ifyoudecideyoudonotwantanynewinformationaboutyoutobecollectedandusedforthestudy(knownas“withdrawalofconsent”),wewillaskyoutosignaformandwillnotcollectanyfurtherinformationfrom you. All information collected, including analysis results frombloodandurinesamplesthathavebeenalreadycollected,willstillbekeptandusedforthestudy.

Ifyouhavepreviouslygivenconsentforustouseleftoverbloodandurine samples and related informationwhichhadbeen collected inthestudy,youmayalsoseparatelywithdrawyourpermissionforthisoptionalpartofthestudyatanypointintime,withoutaffectingyourparticipationinthemainpartofthestudy.Anysamplesthatyounolongerwishforustostoreorusewillbedestroyed.

YouhavetherighttoknowwhatpersonaldatatheUniversityofOxfordandBoehringerIngelheimholdaboutyouandtohaveacopyofthatdata.Yourlocalstudynursecouldprovidethis,however,toensurethestudy’s scientific integrity, youmaynotbeable to reviewsuchdatauntilafterthestudyhasbeencompleted.

Youalsohave the right to correctwrongoroutdatedpersonaldataand request the deletion of your data. However, the study site andBoehringer Ingelheim (as the study’s sponsor) may be obliged bylaw to keep your data to ensure consistency and reproducibility oftheresultsandwecannotdeletedatathathasalreadybeenusedinanalyses(notethatanalysesarerunregularlythroughoutthestudy).

Youalsohavetherighttorestrictorobjecttowhatwedowithyourdata,ortorequestthatyourdatabetransferredelsewhere.However,sometimesthedatacontrollersmaynottobeableto(orhavegroundsnot to) follow a request from you, for example, if we consider thatdeletingyourdatawouldseriouslyharmtheresearch.Ifyouwouldliketoexerciseanyoftheserights,pleasecontactus.Thedataprotection


officerfortheUniversityofOxfordcanbecontactedbyemailat:[email protected].

Ifyouarenothappywiththewaywehavehandledyourdata,youhavethe right to lodgeacomplaintwith the InformationCommissioner’sOffice(telephone03031231113orwww.ico.org.uk).

What if there is a problem during or after the study?YouhavealltheusualrightsofanNHSpatientifyoujointhestudyornot.

The University of Oxford has arrangements in place to provide forharmarisingfromparticipation inthestudy. Intheunlikelyeventofyour being harmed by taking part, insurance cover is provided bythe study sponsor Boehringer Ingelheim International GmbH. AnycompensationwouldbepaidinaccordancewiththeguidelinesoftheAssociationofBritishPharmaceuticalIndustry.

IfyouhaveaconcernaboutanyaspectofthestudyyoucanspeakwiththeEMPA-KIDNEYteambycallinga24-hourFreefonenumber:08081644060. Ifyou remainunhappyabout thestudy inotherwaysandwishtocomplainformally,youcandothisthroughtheNHSComplaintsProcedure.Youcangetdetailsfromyourlocalhospital.

Thank youThankyouforreadingthisleaflet.

Ouraimistomakeyourparticipationaninterestingandworthwhileexperience,whilehelpingusandotherstoimprovethetreatmentofpeoplewhohave,orwhoareatriskof,kidneydisease.

EMPA-KIDNEY Appointment Schedule

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ParticipantInformationLeaflet(UK)V1.324-SEP-2018Participant Information Leaflet (UK) V1.3 24-SEP-2018 IRASNo.:236211Page 24

If you have any questions you can contact the EMPA-KIDNEY team:

By phone:24-hourFreephonenumber:08081644060

By post:EMPA-KIDNEYClinicalTrialServiceUnit(CTSU)RichardDollBuildingUniversityofOxfordRooseveltDriveOXFORD,OX37LF

By email:[email protected]

Or visit our website:www.empakidney.org

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