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Page 1: A Pilot study evaluating whether treatment of scabies with ... · ivermectin tablets have been distributed for both onchocerciasis and lymphatic filariasis. Several Several studies

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APilotstudyevaluatingwhethertreatmentofscabieswithivermectinalso

treatsheadliceIvermectin

IVM-LICE

ISRCTNNCT(clinicaltrials.gov)

V1.016thMay2017

SPONSOR:LondonSchoolofHygiene&TropicalMedicineFUNDERS:WellcomeTrustSTUDYCOORDINATIONCENTRE:LSHTM

LSHTMethicsreference:Pending

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Protocolauthorisedby:

Name: MichaelMarks Role: ChiefInvestigatorSignature: Date: Name: RowenaAsugeni Role: Co-Investigator,AAHSignature: Date: Name: Role: SponsorRepresentativeSignature: Date: MainContacts

TrialManagementGroupChiefInvestigator:MichaelMarksClinicalResearchDepartmentLondonSchoolofHygiene&[email protected]:RowenaAsugeniAtoifiAdventistHospitalAtoifiSolomonIslandsrowenaasugeni@gmail.com

TrialCoordinationCentreForgeneralqueries,supplyoftrialdocumentation,andcollectionofdata,pleasecontact:MichaelMarksClinicalResearchDepartmentLondonSchoolofHygiene&TropicalMedicineMichael.marks@lshtm.ac.ukClinicalQueriesClinicalqueriesshouldbedirectedtoMichaelMarkswhowilldirectthequerytotheappropriateperson.Sponsor

LondonSchoolofHygiene&TropicalMedicine is themainresearchsponsor forthisstudy. For furtherinformationregardingthesponsorshipconditions,pleasecontacttheResearchGovernanceandIntegrityOffice:

LondonSchoolofHygiene&TropicalMedicineKeppelStreetLondonWC1E7HTTel:+442079272626Email:

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FunderThisstudyisfundedaspartofaWellcomeTrustResearchFellowshipheldbyMichaelMarks.This protocol describes the IVM-LICE study andprovides information about procedures for enteringparticipants.The protocol should not be used as a guide for the treatment of other participants; every care was taken in itsdrafting,butcorrectionsoramendmentsmaybenecessary.Thesewillbecirculatedtoinvestigatorsinthestudy,butcentresenteringparticipantsforthefirsttimeareadvisedtocontactthetrialscentretoconfirmtheyhavethemostrecentversion.

Problemsrelatingtothistrialshouldbereferred,inthefirstinstance,tothestudycoordinationcentre.

This trial will adhere to the principles outlined in the International Conference on Harmonisation Good ClinicalPractice(ICHGCP)guidelines,protocolandallapplicablelocalregulations.

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TableofContents1. INTRODUCTION 7 1.1 BACKGROUND 7

2.STUDYOBJECTIVES 8

3.STUDYDESIGN 9 3.1 STUDYOUTCOMEMEASURES 11 3.2 RISKSANDBENEFITS 11

4. SELECTIONANDWITHDRAWALOFPARTICIPANTS 12 4.1 PRE-TREATMENTEVALUATIONS 12 4.2 INCLUSIONCRITERIA 12 4.3 EXCLUSIONCRITERIA. 12 4.4 WITHDRAWALCRITERIA 12

5. TRIALMEDICATION 13

6. SAFETYREPORTINGFORDRUGTRIALS 16 6.1 DEFINITIONS 16 6.2 CAUSALITY 16 6.3 REPORTINGPROCEDURES 17

7. ASSESSMENTANDFOLLOW-UP 19 7.1 LOSSTOFOLLOW-UP 19 7.2TRIALCLOSURE 19

8. STATISTICSANDDATAANALYSIS 20

9.MONITORING 21 9.1 RISKASSESSMENT 21 9.2 MONITORINGATSTUDYCOORDINATIONCENTRE 21 9.3 MONITORINGATLOCALSITE 21

10. REGULATORYISSUES 22 10.1 ETHICSAPPROVAL 22 10.2 CONSENTANDCONFIDENTIALITY 22 10.4 INDEMNITY 22 10.5 SPONSOR 22 10.6 FUNDING 22 10.7 AUDITSANDINSPECTIONS 22

11. TRIALMANAGEMENT 23

12. PUBLICATIONPOLICY 24

13. REFERENCES 25

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GLOSSARYOFABBREVIATIONSAAH AtoifiAdventistHospitalAE AdverseEventSAE SeriousAdverseEventSUSAR SeriousUnexpectedEventKEYWORDSScabiesIvermectinImpetigoHeadlice

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STUDYSUMMARY

TITLE A Pilot study evaluatingwhether treatment of scabieswithivermectinalsotreatsheadliceIvermectin

DESIGN Prospectivebeforeandafterpilotstudy

AIMS Assesstheimpactofascabiestreatmentprogrammeontheprevalenceofheadlice

inthesamecommunity.

OUTCOMEMEASURES PrimaryOutcome

a)Changeinprevalenceofheadlicebetweenbaselineandfollow-up

POPULATION Treatmentisprovidedtoalleligibleresidentsforscabies.Atotalpopulationof

approximately150individualswillbetreated

ELIGIBILITY AllresidentsoftheAtoifiHospitalCampusareeligibletoparticipateinthestudy

TREATMENT Treatmentofscabies:

Standardtreatmentinlinewithguidelines:

EitheranoraldoseofIvermectin(200μg/kg)orpermethrincreamand

malathionshampooforthosewithacontraindicationtoIvermectin(WT<15kg,

pregnantorbreastfeedingwomen)givenin2doses7-14daysapart.

DURATION 3months

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1. INTRODUCTION1.1 BACKGROUND Scabiesandheadlicearebothcommonworldwideectoparaisticinfectionsandscabiesinparticularisa

significantpublichealthproblemsinthePacific[1].Ivermectinisaneffectivetreatmentforboth

conditions.Communitymasstreatmentisnowtherecognisedbestapproachtotreatingscabiesand

householdtreatmentisalsocommonlyusedforheadlicetreatment[2,3].Asivermectinisusedtotreat

bothconditionsitwouldbeanticipatedthatprogrammaticscabiestreatmentinacommunitywouldalso

treatheadlice.Theaimofthissmallscalepilotstudyistoevaluatethishypothesis.

1.2 RATIONALEFORCURRENTSTUDY

Ivermectinisknowntohaveabroadrangeofparasiticactivitiesandiseffectiveattreatingmany

ectoparasiticinfections.Itisnowconsideredtheoptimumdrugforcommunitytreatmentofscabies.The

drugisalsoknowntobeeffectivefortreatingheadlicebutnostudieshaveformallyassessedwhether

communitytreatmentforscabiesalsoreducesheadliceprevalence.Thisstudywillhelpusmorefully

understandanyadditionalbenefitonheadlicewhencommunitiesaretreatedforscabies

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2.STUDYOBJECTIVES

StudyAims:

Assesstheimpactofascabiestreatmentprogrammeontheprevalenceofheadliceinthesame

community.

PrimaryObjective:

Theprimaryobjectiveistoseewhethercommunitytreatmentforscabiesalsoreducestheprevalenceof

headlice.

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3.STUDYDESIGN

This is a pilot open-label study measuring the impact of scabies treatment on head lice prevalence in the

same individuals. In line with recommendations the treatment is provided at the community level.

StudySite

ThisstudywillbeconductedonthecampusofAtoifiAdventistHospital.Allstaffandtheirfamiliesliving

onthecampuswillbeinvitedtoparticipate.BasedoninputfromcollaboratorsatAtoificampusitis

recognisedthatheadliceisacommonproblemparticularlyamongstchildrenlivingonthehospital

campus.Treatment will be provided at the level of the community in line with recommendations and best

evidence for scabies. Allindividualsonthecampuswillbeofferedtreatmentandwillbeinvitedto

participateinthestudy.

Treatment will be provided at the level of the community in line with recommendations and best evidence

for scabies. Allindividualswillbeinvitedtoparticipateinthestudyandwillbeofferedtreatment.

CommunityAwareness

Priortothestudycommencingwewillengagecommunityleadersonatthehospitalcampus.Aresearch

trainingworkshopwillbeheldatAAHandwhichwillbeattendedbyAAHandotherstudystaffaswellas

keycommunityleaders.Thismeetingwillprovideanopportunityforexplanationofthestudyaimsand

methodologiesandforstudystafftoanswerquestionsaboutthestudydesignandimplementation.

EligibilityCriteria:

AllresidentsoftheAtoifiHospitalcampuswillbeinvitedtoparticipateinthestudy.

InclusionCriteria:

Allresidentsoftheselectedcommunitieswillbeinvitedtoparticipateinthestudy.

ExclusionCriteria:

Individualswithacontra-indicationtotreatment.

Individualsnotconsentingtoparticipate.

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Duration

Thedurationofthestudyis3months.Forallparticipants,therewillbea15dayon-studyperiod

whichwillincludetwovisitsbythestudyteam

• Day1forbaselinemedicalassessmentanddeliverytreatment

• Day8-15fordeliveryofseconddoseoftreatment

Treatment

Noinvestigationalmedicationsorindicationsarebeingassessed.Allindividualswillreceivestandard

treatmentforscabies.

Treatmentofscabies:

• Day1forbaselinemedicalassessmentanddeliveryofivermectin(orpermethrin&malathion

whencontra-indicated)

• Day8fordeliveryofseconddoseofivermectin

AnoraldoseofIvermectin(200μg/kg).

Inindividualswithacontra-indication(pregnancy,breast-feeding,weight<15kg)permethrincreamand

malathionshampoowillbeofferedinstead.

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3.1 STUDYOUTCOMEMEASURES PrimaryOutcome

a)Changeinprevalenceofheadlicebetweenbaselineandfollow-up

SampleSize

Therequiredsamplesizewascalculatedtobe150individualsbasedonthefollowingassumptions.

• Pre-treatmentprevalenceofheadiceofabout25%

• Post-treatmentprevalenceofheadliceofabout10%

• Enrolment80%

Dataandallappropriatedocumentationwillbestoredforaminimumof5yearsafterthecompletion

ofthestudy,includingthefollow-upperiod.

3.2 RISKSANDBENEFITS

Thesafetyprofileofivermectinisverywellknown.Safetyhasbeenwellstudiedthroughitsusage

therapeuticallyandinlargescaleMDAprograms.Inthepast21years,morethan1billiondosesof

ivermectintabletshavebeendistributedforbothonchocerciasisandlymphaticfilariasis.Several

studiesofpregnantwomenaccidentallygivenivermectinshowednoevidenceofteratogenicity[4–6].

Participantswillbenefitfromreceivingtreatmentforscabiesandheadliceaspartofthestudy.Theseare

bothmajorpublichealthproblemsintheSolomonIslandsandparticipantswillthereforegainbenefit

fromreceivingthebestavailabletreatmentfortheseconditionswhich,itisbelieved,willresultin

improvementsintheirhealthandwellbeing.

BenefitstoCommunities

Communitieswillbenefitfromreceivingtreatmentforscabiesaspartofthesestudies.Thisisamajor

publichealthproblemsintheSolomonIslandsandparticipantswillthereforegainbenefitfromreceiving

thebestavailabletreatmentforthisconditionwhich,itisbelieved,willresultinimprovementsintheir

healthandwellbeing.

BlindingThisisanopen-labelstudy

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4. SELECTIONANDWITHDRAWALOFPARTICIPANTS4.1 PRE-TREATMENTEVALUATIONSTreatmentofthewholecommunitywithIvermectinandPermethrinisthebestavailabletreatment

forthepurposeofscabiescontrol.Individualtreatmentresultsinre-infestationandtreatment

failure.Inlinewithrecommendationthereforetreatmentsisofferedtoallindividualsregardlessof

thepresence/absenceofclinicalfeaturesofeitherdisease.

4.2 INCLUSIONCRITERIAAllconsentingindividualsintheparticipatingcommunitieswillbeeligibletoparticipate

4.3 EXCLUSIONCRITERIA.Individualsnotconsentingtoparticipateinthestudy.

Individualswhoareunwellonthedaythatstudymedicationsareadministered.

4.4 WITHDRAWALCRITERIAStudyparticipationisvoluntaryandstudyparticipantscanwithdrawatanytime.Thenumberofwithdrawalswillberecordedandonlydatacollectedpriortowithdrawalwillbeincludedintheanalysis.Onlydatacollectedpriortowithdrawalwillbeincludedintheanalysis.

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5. TRIALMEDICATION5.1 Nameanddescriptionofinvestigationalmedicinalproduct(s)Noinvestigationaltreatmentsarebeingtried.Ivermectin(andpermethrin)isarecognisedtreatmentforscabiesandisontheSolomonIslandsEssentialDrugListforthisindication.Ivermectin

Ivermectinisananthelminthic.Ivermectinismetabolizedintheliver,andivermectinand/orits

metabolitesareexcretedalmostexclusivelyinthefecesoveranestimated12days,withlessthan1%

oftheadministereddoseexcretedintheurine.Afteroraladministration,theapparentplasmahalf-

lifeofivermectinisapproximately16hours.Ivermectinisindicatedforthetreatmentof

onchocerciasisorriverblindnesscausedbyOnchocercavolvulusandforstrongyloidiasiscausedby

Strongyloidesstercoralis.Therecommendeddosagefortreatmentofscabiesistwooraldoses

designedtoprovideapproximately200μgofivermectinperkgofbodyweight.Thesamedoseis

recommendedintheSolomonIslands.Ivermectinisavailablein3mgtablets.

Topical5%permethrincream(Lyclear®)

Topical5%permethrin(Lyclear®)creamforscabiesissuppliedina30gtube.Thecreamisapplied

alloverthebodyincludingfromnecktotoeandwashedoffafteraminimumof8hrs.Forchildren

aged2monthsorlesspermethrinshouldbewashedoffafter4hours.

5.2 Legalstatusofdrug

PermethrinislicencedintheUKforthetreatmentofscabies.Itislistedasontheessentialmedicines

listfortheSolomonIslandsandrecommendedasapotentialtreatmentforscabies.

IvermectinisnotlicencedforthetreatmentofscabiesintheUKalthoughNICEhasprovidedguidance

onitsuse(https://www.nice.org.uk/advice/esuom29/resources/ivermectin-for-difficulttotreat-

scabies-17546902981).IvermectiniswidelyusedincontrolprogrammesforbothOnchocerciasis

andLymphaticFilariasis.IvermectinislistedasontheessentialmedicineslistfortheSolomon

Islandsandrecommendedasapotentialtreatmentforscabies.

5.4 DrugStorageandSupplyMedicationswillarrivebyplaneandwillreachtheislandsbyboatattheprovincialpharmacy/

medicalstore.Theorderrequestwillbecheckedwiththesuppliesdelivered.Thedeliverynotice

number,deliverydateandthemedicationsbatchnumberwillberecordedinalogbook.Medications

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willbetakenoutofthepharmacyinbulkbythestudyteamsfordispensinginthecommunity.Study

teamswillmaintainalogofallmedicinesdispensedthatcanbecross-checkedagainstparticipants

studyrecords.

5.5 PreparationandlabellingofIMPFor participants receiving ivermectin, the dose will be determined according to body weight and

treatment will be administered under direct supervision of the study team. Drug administration will be

recorded in a standardized record form.

Participants assigned to permethrin (due to contra-indication to ivermectin) will receive a tube of cream

and will be asked apply the cream from neck to toes before they leave the clinic and under supervision of

a study nurse, and leave it on for a minimum of 8 hours, maximum 24 hours if possible. For children aged

2 months or less, cream will applied for a maximum of 4 hours.

5.6 Dosageschedules/modificationsInlinewithstandardtreatmentthedosingofIvermectinwillusethefollowingweightbands

PermethrinwillbeusedinsteadofIvermecitninthefollowingcircumstances

• Pregnancy• Breastfeeding• Child<6monthsage• Child<15kg

Wherepermethrinisindicatedthefollowingstandarddosingprotocolwillbeused:

• Full tube for adults. • Half tube for children. • Apply to whole body and leave on for 1 day before washing off

5.7 Knowndrugreactionsandinteractionwithothertherapies

WEIGHT IVERMECTIN TABLETS (3mg Tabs)

<15KG PERMETHRIN CREAM

15KG 1 25 – 37.5 KG 2 37.5 – 50 KG 3

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Thesafetyprofileofivermectiniswell

establishedfromlargemasstreatment

campaignswhere>100milliondoseshavebeenadministered.Themostcommonlyreportedside

effectsareforIvermectinareheadache,dizziness,itch.Adverseeventsarenormallymildandself-

limitingwithnospecifictherapyrequired.Permethrindoesnotcommonlycauseanysystemic

adversecommons.

5.8 ConcomitantmedicationIndividualsreceivingWarfarinmaynotreceivetreatmentwithIvermectinduetopotential

interactions.NoindividualsoutsideofthecapitaloftheSolomonIslands(Honiara)arereceiving

WarfarinduetoalackofINRmonitoringfacilitiesandthereforeitisnotanticipatedthatany

individualsinthestudywillbereceivingacontra-indicatedconcomitantmedication.Permethrinwill

beofferedifapatienttakingwarfarinwasidentified.

5.9 TrialrestrictionsTherearenotrialrestrictions.

Asnotedabovepregnantandbreastfeedingwomenandchildren<15kgwillbeofferedpermethrin

ratherthanivermectinbutwillstillbeallowedtoparticipateinthestudy.

5.10 AssessmentofcomplianceDrugswillbedeliveredasasingleobservedtreatmentandthereforecompliancewillbeassessedat

thetimeofdrugdistribution.

50-75 KG 4 >75 KG 5

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6. SAFETYREPORTINGFORDRUGTRIALS6.1 DEFINITIONSTerm DefinitionAdverse Event(AE)

Anyuntowardmedicaloccurrenceinaparticipanttowhomamedicinalproducthasbeenadministered, includingoccurrenceswhicharenotnecessarilycausedbyorrelatedtothatproduct.An AE can therefore be any unfavourable and unintended sign (including anabnormal laboratory finding), symptom, or disease temporally associatedwiththeuseofaninvestigationalmedicinalproduct(IMP),whetherornotconsideredrelatedtotheIMP.

Adverse Reaction(AR)

Any untoward and unintended response in a participant to an investigationalmedicinalproductwhichisrelatedtoanydoseadministeredtothatparticipant.The phrase “response to an investigational medicinal product” means that acausalrelationshipbetweenatrialmedicationandanAEisatleastareasonablepossibility,i.e.therelationshipcannotberuledout.All cases judgedbyeither the reportingmedicallyqualifiedprofessionalor theSponsor as having a reasonable suspected causal relationship to the trialmedicationqualifyasadversereactions.

Serious AdverseEvent(SAE)

Aseriousadverseeventisanyuntowardmedicaloccurrencethat:• Resultsindeath• Islife-threatening• Requiresinpatienthospitalisationorprolongationofexistinghospitalisation• Resultsinpersistentorsignificantdisability/incapacity• ConsistsofacongenitalanomalyorbirthdefectOther ‘important medical events’ may also be considered serious if theyjeopardisetheparticipantorrequireaninterventiontopreventoneoftheaboveconsequences.

Serious AdverseReaction(SAR)

An adverse event that is both serious and, in the opinion of the reportinginvestigator, believedwith reasonable probability to be due to one of the trialtreatments,basedontheinformationprovided.

SuspectedUnexpectedSerious AdverseReaction(SUSAR)

A serious adverse reaction, the nature and severity of which is not consistentwiththeinformationaboutthemedicinalproductinquestionsetout:• In the caseof aproductwith amarketingauthorisation, in the summaryofproductcharacteristics(SmPC)forthatproduct

• Inthecaseofanyotherinvestigationalmedicinalproduct,intheinvestigatorbrochure(IB)relatingtothetrialinquestion.

6.2 CAUSALITYMostadverseeventsandadversedrugreactionsthatoccurinthisstudy,whethertheyareseriousornot,will be expected treatment-related side effects due to thedrugsused in this study. The assignment ofcausality should be made by the investigator responsible for the care of the participant using thedefinitionsinthetablebelow.Ifanydoubtaboutthecausalityexiststhelocalinvestigatorshouldinformthestudycoordinationcentrewhowill notify theChief Investigators. Thepharmaceutical companies and/orother cliniciansmaybeaskedtoadviseinsomecases.

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Inthecaseofdiscrepantviewsoncausalitybetweentheinvestigatorandothers,allpartieswilldiscussthecase.Intheeventthatnoagreementismade,bothpointsofviewaretobereported.Relationship DescriptionUnrelated ThereisnoevidenceofanycausalrelationshipUnlikely Thereislittleevidencetosuggestthereisacausalrelationship(e.g.theeventdid

notoccurwithinareasonabletimeafteradministrationofthetrialmedication).Thereisanotherreasonableexplanationfortheevent(e.g.theparticipant’sclinicalcondition,otherconcomitanttreatment).

Possible Thereissomeevidencetosuggestacausalrelationship(e.g.becausetheeventoccurswithinareasonabletimeafteradministrationofthetrialmedication).However,theinfluenceofotherfactorsmayhavecontributedtotheevent(e.g.theparticipant’sclinicalcondition,otherconcomitanttreatments).

Probable Thereisevidencetosuggestacausalrelationshipandtheinfluenceofotherfactorsisunlikely.

Definitely Thereisclearevidencetosuggestacausalrelationshipandotherpossiblecontributingfactorscanberuledout.

Notassessable Thereisinsufficientorincompleteevidencetomakeaclinicaljudgementofthecausalrelationship.

6.3 REPORTINGPROCEDURESDependingonthenatureoftheeventthereportingproceduresbelowshouldbefollowed.Anyquestionsconcerning adverse event reporting should be directed to the study coordination centre in the firstinstance.6.3.1NonseriousAdverseReactions(ARs)/AdverseEvents(AEs)GiventheestablishedsafetyprofileofthedrugsbeingusedinthisstudyandthefactthattheyarebeingusedforestablishedindicationswewillonlycollectdataonSAEsandSUSARs.6.3.2SeriousAdverseReactions(SARs)/SeriousAdverseEvents(SAEs)Serious Adverse Events (SAEs) and Serious Adverse Reactions (SARs) should be reported to the studycoordinationcentrewithin24hoursofthelocalsitebeingmadeawareoftheevent.AnSAEformshouldbecompletedandsubmittedtothestudycoordinationcentrewithasmuchdetailofthe event that is available at that time. If awaiting further details, a follow up SAE report should besubmittedpromptlyuponreceiptofanyoutstandinginformation. TheCI(forasingle-centretrial)orPI(for a multi-centre trial) must record the event with an assessment of seriousness, causality andexpectedness.Anyeventsrelatingtoapre-existingconditionoranyplannedhospitalisationsforelectivetreatmentofapre-existingconditiondonotneedreportingasSAEs.6.3.3SUSARsAllSAEsassignedbythePIordelegateasbothsuspectedtoberelatedtoIMP-treatmentandunexpectedwillbeclassifiedasSUSARsandwillbesubjecttoexpeditedreportingtotheRegulatoryAuthority,intheUK: Medicines and Healthcare Products Regulatory Agency (MHRA). The Sponsor (or delegate) willinform the MHRA, and the ethics committee of UK-relevant SUSARs within the required expeditedreportingtimescales(asperLSHTMStandardOperatingProcedureforrecording,managingandreportingofadverseeventsforIMPstudies).Forblindedtrials,allSUSARsmustbereportedassumingtheactivecompoundisinvolved.Inthecaseofasuspected,unexpected,seriousadversereactions(SUSAR),thestaffatthesiteshould:

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1. Contactthestudycoordinationcentreimmediatelybyphoneoremailtoinformthemoftheevent.2. Submit a completed SAE form (signed and dated) within 24 hours, together with relevant

treatmentformsandanonymisedcopiesofallrelevantinvestigations.3. Submitanyadditionalinformationpromptlyuponrequest.

ContactdetailsforreportingSAEsandSUSARsTelephone:+6777738438/+447984643424

Email:[email protected]

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7. ASSESSMENTANDFOLLOW-UPDataCollection

Atbaselineallindividualswillundergoastandardizedexaminationtocollectdataonthepresenceof

scabies,impetigoandheadlice.Followingexaminationindividualswillbeweighedanddirectlyobserved

treatmentwillbedispensedinlinewithstandardtreatmentguidelines(seebelow).Individualswillbere-

examinedat48hourstoassessimmediatekillingofhead-lice,againat2weeksand3months.

Nosamplesarecollectedaspartofthisstudy

7.1 LOSSTOFOLLOW-UPThisisnotanindividuallyrandomisedclinicaltrialbutallowancehasbeenmadeforlosstofollow-upin

thesamplesizecalculation.

7.2TRIALCOMPLETION

Thetrialisplannedtorunovera3monthperiod.Thetrialwillbecompleteattheendofthis3month

period.

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8. STATISTICSANDDATAANALYSISSampleSize

Therequiredsamplesizewascalculatedtobe150individualsbasedonthefollowingassumptions.

• Pre-treatmentprevalenceofheadiceofabout25%

• Post-treatmentprevalenceofheadliceofabout10%

• Enrolment80%

PrimaryOutcomea)Changeinprevalenceofheadlicebetweenbaselineandfollow-up

Dataandallappropriatedocumentationwillbestoredforaminimumof10yearsafterthe

completionofthestudy,includingthefollow-upperiod.

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9.MONITORING9.1 RISKASSESSMENTThisisconsideredalowriskstudy.

Allthedrugsbeingusedarebeingprescribedforroutineindicationsandhavewellestablishedsafety

profiles.Assuchonlypassivemonitoringforadverseeventswillbeundertakenduringthestudy.

9.2 MONITORINGATSTUDYCOORDINATIONCENTREDatawillbeentereddirectlyintoanelectronicdatabaseatthetimeofthestudy.Consentformswill

bereviewedtoensurecompletioninlinewithGCPstandards.

9.3 MONITORINGATLOCALSITESitevisitswilltakeplaceatD1(treatmentscabies),D8(secondtreatmentforscabies)andmonth3

(assessmentofoutcome).Arandomselectionofconsentformsanddatacollectionformswillbe

reviewedatthebaselinevisitsandadverseeventanddatacollectionformsateachsubsequentvisit.

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10. REGULATORYISSUES10.1 ETHICSAPPROVALThe Study Coordination Centre has applied for ethics approval from the LSHTM Research EthicsCommittee,aswellastheSolomonIslandsNationalEthicsBoardandtheAtoifiAdventistHospitalEthicsCommittee.Substantialprotocolamendmentswillnotbe implementeduntil a favourableopinionhasbeengrantedfromboththeethicscommittee.Correspondencefrombothethicscommitteeswillbemaintainedinthetrialmasterfile.Asthedurationofthestudyis3monthstheannualprogressreportwillaccompanythenotificationoftheendofthestudy.10.2 CONSENTANDCONFIDENTIALITYPriortoperforminganystudyspecificprocedure,writteninformedconsentwillbeobtainedforeachsubject.Informationsheetsexplainingthestudywillbedistributedtocommunitynurseswhowillbetrainedinexplainingthestudy.Forsubjectsbelowthelegalage,aparentorlegalguardianmustprovideconsent.Writtenconsentwillbeobtainedinlocaldialectonalloccasions.10.3 ConfidentialityAlldatawillbefully-anonymised.AcopyofthedatabasewillbeheldbothatAtoifiHospitalandLSHTM.Thestudydatabasewillnotcontainanypatientidentifiableinformation.FormswillberetainedatAtoifiAdventistHospital.10.4 INDEMNITYLondonSchoolofHygiene&TropicalMedicineholdsPublicLiability("negligentharm")andClinicalTrial("non-negligentharm")insurancepolicieswhichapplytothistrial.10.5 SPONSORLondon School of Hygiene& TropicalMedicinewill act as themain sponsor for this study. Delegatedresponsibilitieswillbeassignedlocally.10.6 FUNDINGThisstudyisfundedaspartofaWellcomeTrustResearchFellowshipheldbyMichaelMarks.Nopaymentswillbemadetopatientsparticipatinginthisstudy.10.7 AUDITSANDINSPECTIONSThestudymaybesubjectauditbytheLondonSchoolofHygiene&TropicalMedicineundertheirremitassponsor,theStudyCoordinationCentreandotherregulatorybodiestoensureadherencetoGCP.

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11. TRIALMANAGEMENTATrialManagementGroup(TMG)willbeappointedandwillberesponsibleforoverseeingtheprogressofthetrial.Theday-to-daymanagementofthetrialwillbeco-ordinatedbyMichaelMarksandJasonDiau.All treatments in the study are being given for standard indications and the drugs have known safetyprofilesincludinginthesettingofco-administration.ADSMBwillthereforenotbeappointed.AlldatawillbeheldjointlybyLSHTMandAAH.DatawillbestoredonanencryptedpasswordprotectedserveratbothLSHTMandAAH.

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12. PUBLICATIONPOLICYAllpublicationsandpresentationsrelatingtothestudywillbeauthorisedbytheTrialManagementGroup.ThefirstpublicationofthetrialresultswillbeinthenameoftheTrialManagementGroup,ifthisdoesnotconflictwiththe journal’spolicy. If therearenamedauthors, thesewill includeat least thetrial’sChiefInvestigator,StatisticianandTrialCoordinator.MembersoftheTMGandtheDataMonitoringCommitteewillbelistedandcontributorswillbecitedbynameifpublishedinajournalwherethisdoesnotconflictwiththejournal’spolicy.AuthorshipofparallelstudiesinitiatedoutsideoftheTrialManagementGroupwillbeaccordingtotheindividualsinvolvedintheprojectbutmustacknowledgethecontributionoftheTrialManagementGroupandtheStudyCoordinationCentre.

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13. REFERENCES1 MarksM,VahiV,SokanaO,etal.MappingtheEpidemiologyofYawsintheSolomonIslands:ACluster

RandomizedSurvey.AmJTropMedHyg2015;92:129–33.doi:10.4269/ajtmh.14-0438

2 InternationalAssociationforthePreventionofBlindness.TrachomaMappinginthePacific.2013.

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4 EmersonPM,BurtonMJ,SolomonAW,etal.TheSAFEstrategyfortrachomacontrol:usingoperationalresearchforpolicy,andimplementation.BullWorldHealthOrgan2006;84:613–9.

5 SadiqST,GlasgowKW,DrakelyCJ,etal.EffectsofazithromycinonmalariometricindicesinTheGambia.TheLancet1995;346:881–2.doi:10.1016/S0140-6736(95)92712-3

6 KeenanJD,AyeleB,GebreT,etal.ChildhoodMortalityinaCohortTreatedWithMassAzithromycinforTrachoma.ClinInfectDis2011;52:883–8.doi:10.1093/cid/cir069

7 ColesCL,MabulaK,SeidmanJC,etal.Massdistributionofazithromycinfortrachomacontrolisassociatedwithincreasedriskofazithromycin-resistantStreptococcuspneumoniaecarriageinyoungchildren6monthsaftertreatment.ClinInfectDisOffPublInfectDisSocAm2013;56:1519–26.doi:10.1093/cid/cit137

8 RomaniL,SteerAC,WhitfeldMJ,etal.Prevalenceofscabiesandimpetigoworldwide:asystematicreview.LancetInfectDis2015;15:960–7.doi:10.1016/S1473-3099(15)00132-2

9 HeukelbachJ,FeldmeierH.Scabies.TheLancet2006;367:1767–74.doi:10.1016/S0140-6736(06)68772-2

10 RomaniL,WhitfeldMJ,KoroivuetaJ,etal.MassDrugAdministrationforScabiesControlinaPopulationwithEndemicDisease.NEnglJMed2015;373:2305–13.doi:10.1056/NEJMoa1500987

11 MarksM,VahiV,SokanaO,etal.ImpactofCommunityMassTreatmentwithAzithromycinforTrachomaEliminationonthePrevalenceofYaws.PLoSNeglTropDis2015;9:e0003988.doi:10.1371/journal.pntd.0003988

12 MitjàO,HouineiW,MosesP,etal.MassTreatmentwithSingle-DoseAzithromycinforYaws.NEnglJMed2015;372:703–10.doi:10.1056/NEJMoa1408586

13 TaplinD,PorcelainSL,MeinkingTL,etal.Communitycontrolofscabies:amodelbasedonuseofpermethrincream.Lancet1991;337:1016–8.

14 ChippauxJP,Gardon-WendelN,GardonJ,etal.Absenceofanyadverseeffectofinadvertentivermectintreatmentduringpregnancy.TransRSocTropMedHyg1993;87:318.

15 GyapongJO,ChinbuahMA,GyapongM.Inadvertentexposureofpregnantwomentoivermectinandalbendazoleduringmassdrugadministrationforlymphaticfilariasis.TropMedIntHealthTMIH2003;8:1093–101.

16 PacquéM,MuñozB,PoetschkeG,etal.Pregnancyoutcomeafterinadvertentivermectintreatmentduringcommunity-baseddistribution.LancetLondEngl1990;336:1486–9.

17 CoulibalyYI,DickoI,KeitaM,etal.AclusterrandomizedstudyofthesafetyofintegratedtreatmentoftrachomaandlymphaticfilariasisinchildrenandadultsinSikasso,Mali.PLoSNeglTropDis2013;7:e2221.doi:10.1371/journal.pntd.0002221

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