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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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2 InternationalAssociationforthePreventionofBlindness.TrachomaMappinginthePacific.2013.
3 TheWorldHealthOrganisation.Eradicationofyaws-theMorgesStrategy.WklyEpidemiolRec2012;87:189–94.
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