Conditions: Scabies Head Lice
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 118
Healthy volunteers: yes

Brief summary:
This is a pilot study evaluating if treatment for scabies also treats headlice in the same community

Detailed description:
Background:

Scabies and head lice are both ubiquitous ectoparasitic infections that have been identified as common public health problems in the Pacific Island Country Territories. Mass drug administration using ivermectin is increasingly recognised as an effective strategy for scabies treatment and control, however, its possible impact on prevalence of head lice has not been evaluated. Given that oral ivermectin is an effective treatment option for pediculosis capitis, we hypothesise that community treatment with ivermectin for scabies would also provide benefit by reducing prevalence of head lice infestation in the community. We aim to test this hypothesis with a small-scale pilot study in the Solomon Islands.

Methodology:

The study would be carried out at the Atoifi Adventist Hospital campus, on the North-Eastern coast of the island of Malaita. The campus houses an estimated 180 individuals and all residents would be invited to participate in the study and be offered treatment.

At baseline all individuals would undergo a standardized examination to collect data on the presence of scabies, impetigo and head lice. Following examination individuals would be weighed and given directly observed standard treatment for scabies.

Treatment for scabies consists of one oral dose of ivermectin (200 micrograms per kilogram) at day 1 and at day 8.

Individuals with contra-indications (pregnancy, breast feeding, weight under 15kg) would be offered the alternative of 5% permethrin cream and malathion shampoo.

Individuals would be re-examined at 48hours (to assess immediate killing of head lice) and again at 2 weeks. Final follow-up will be at 3 months to establish: 1) whether changes in head lice prevalence have been sustained 2) what the impact of treatment on scabies and impetigo with ivermectin is in this specific community.

Arms:
arm 1: This study consists of a single treatment arm. Patients will receive Ivermectin or where contraindicated (Pregnancy, Breastfeeding, Weight \<15kg) Permethrin Cream and Malathion shampoo

Interventions: intervention 1: Ivermectin intervention 2: Permethrin 5% intervention 3: Malathion Shampoo 0.5%
Intervention descriptions: intervention 1: A single weight based dose of ivermectin intervention 2: Permethrin cream is used in conjunction with Malathion shampoo when ivermectin is contra-indicated intervention 3: Permethrin cream is used in conjunction with Malathion shampoo when ivermectin is contra-indicated

Protocol document:
Prot_SAP_000.pdf: 
IVM-LICE 
Page 1 of 26 
 Version 1.0 16/05/17 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A Pilot study evaluating whether treatment of scabies with ivermectin also 
treats headlice Ivermectin 
 
IVM-LICE 
 
 
ISRCTN 
NCT (clinicaltrials.gov) 
 
 
 
V1.0 
16th May 2017 
 
 
 
 
 
 
SPONSOR: London School of Hygiene & Tropical Medicine  
FUNDERS: Wellcome Trust 
STUDY COORDINATION CENTRE: LSHTM 
 
LSHTM ethics reference: Pending 
 
 
 
 
 
 
 
 
 
 
 
 


IVM-LICE 
Page 2 of 26 
 Version 1.0 16/05/17 
 
 
 
 
Protocol authorised by: 
 
Name:  
Michael Marks 
Role: Chief Investigator 
Signature: 
 
Date:   
 
 
  
Name: 
Rowena Asugeni 
Role: Co-Investigator, AAH 
Signature: 
 
Date:   
 
 
  
Name: 
 
Role: Sponsor Representative 
Signature: 
 
Date:   
 
 
  
Main Contacts 
 
Trial Management Group 
 
Chief Investigator:  
Michael Marks 
Clinical Research Department 
London School of Hygiene & Tropical Medicine 
Michael.marks@lshtm.ac.uk 
 
Co-investigators:  
Rowena Asugeni 
Atoifi Adventist Hospital 
Atoifi 
Solomon Islands 
rowenaasugeni@gmail.com 
 
 
Trial Coordination Centre 
For general queries, supply of trial documentation, and collection of data, please contact: 
 
Michael Marks 
Clinical Research Department 
London School of Hygiene & Tropical Medicine 
Michael.marks@lshtm.ac.uk 
 
 
 
Clinical Queries 
Clinical queries should be directed to Michael Marks who will direct the query to the appropriate person. 
 
Sponsor 
 
 
London School of Hygiene & Tropical Medicine is the main research sponsor for this study.  For further 
information regarding the sponsorship conditions, please contact the Research Governance and Integrity 
Office: 
 
 
 
London School of Hygiene & Tropical Medicine 
Keppel Street 
London WC1E 7HT 
Tel: +44 207 927 2626 
Email:  
 


IVM-LICE 
Page 3 of 26 
 Version 1.0 16/05/17 
Funder 
This study is funded as part of a Wellcome Trust Research Fellowship held by Michael Marks. 
 
This protocol describes the IVM-LICE study and provides information about procedures for entering participants. 
The protocol should not be used as a guide for the treatment of other participants; every care was taken in its 
drafting, but corrections or amendments may be necessary. These will be circulated to investigators in the study, but 
centres entering participants for the first time are advised to contact the trials centre to confirm they have the most 
recent version.  
 
Problems relating to this trial should be referred, in the first instance, to the study coordination centre.  
 
This trial will adhere to the principles outlined in the International Conference on Harmonisation Good Clinical 
Practice (ICH GCP) guidelines, protocol and all applicable local regulations.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


IVM-LICE 
Page 4 of 26 
 Version 1.0 16/05/17 
 
Table of Contents 
 
1. INTRODUCTION 
7 
1.1 
BACKGROUND 
7 
2.  STUDY OBJECTIVES 
8 
3.  STUDY DESIGN 
9 
3.1 
STUDY OUTCOME MEASURES 
11 
3.2 
RISKS AND BENEFITS 
11 
4. SELECTION AND WITHDRAWAL OF PARTICIPANTS 
12 
4.1 
PRE-TREATMENT EVALUATIONS 
12 
4.2 
INCLUSION CRITERIA 
12 
4.3 
EXCLUSION CRITERIA. 
12 
4.4 
WITHDRAWAL CRITERIA 
12 
5. TRIAL MEDICATION 
13 
6. SAFETY REPORTING FOR DRUG TRIALS 
16 
6.1 
DEFINITIONS 
16 
6.2 
CAUSALITY 
16 
6.3 
REPORTING PROCEDURES 
17 
7. ASSESSMENT AND FOLLOW-UP 
19 
7.1 
LOSS TO FOLLOW-UP 
19 
7.2TRIAL CLOSURE 
19 
8. STATISTICS AND DATA ANALYSIS 
20 
9. MONITORING 
21 
9.1 
RISK ASSESSMENT 
21 
9.2 
MONITORING AT STUDY COORDINATION CENTRE 
21 
9.3 
MONITORING AT LOCAL SITE 
21 
10. REGULATORY ISSUES 
22 
10.1 
ETHICS APPROVAL 
22 
10.2 
CONSENT AND CONFIDENTIALITY 
22 
10.4 
INDEMNITY 
22 
10.5 
SPONSOR 
22 
10.6 
FUNDING 
22 
10.7 
AUDITS AND INSPECTIONS 
22 
11. TRIAL MANAGEMENT 
23 
12. PUBLICATION POLICY 
24 
13. REFERENCES 
25 
 


IVM-LICE 
Page 5 of 26 
 Version 1.0 16/05/17 
 
 
GLOSSARY OF ABBREVIATIONS 
AAH 
Atoifi Adventist Hospital 
AE 
Adverse Event 
SAE 
Serious Adverse Event 
SUSAR 
Serious Unexpected Event 
 
KEYWORDS 
Scabies 
Ivermectin 
Impetigo 
Headlice 


IVM-LICE 
Page 6 of 26 
 Version 1.0 16/05/17 
 
STUDY SUMMARY 
 
TITLE A Pilot study evaluating whether treatment of scabies with 
ivermectin also treats headlice Ivermectin 
 
DESIGN Prospective before and after pilot study  
AIMS Assess the impact of a scabies treatment programme on the prevalence of headlice 
in the same community.  
 
OUTCOME MEASURES Primary Outcome 
a) Change in prevalence of headlice between baseline and follow-up 
 
POPULATION Treatment is provided to all eligible residents for scabies. A total population of 
approximately 150 individuals will be treated 
  
ELIGIBILITY All residents of the Atoifi Hospital Campus are eligible to participate in the study 
TREATMENT Treatment of scabies: 
Standard treatment in line with guidelines: 
Either an oral dose of Ivermectin (200μg/kg) or permethrin cream and 
malathion shampoo for those with a contraindication to Ivermectin (WT<15kg, 
pregnant or breastfeeding women) given in 2 doses 7-14 days apart.  
 
DURATION 3 months 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


IVM-LICE 
Page 7 of 26 
 Version 1.0 16/05/17 
1. 
INTRODUCTION  
 
1.1 
BACKGROUND 
 
 
Scabies and headlice are both common worldwide ectoparaistic infections  and scabies in particular is a 
significant public health problems in the Pacific[1].  Ivermectin is an effective treatment for both 
conditions. Community mass treatment is now the recognised best approach to treating scabies and 
household treatment is also commonly used for headlice treatment[2,3]. As ivermectin is used to treat 
both conditions it would be anticipated that programmatic scabies treatment in a community would also 
treat head lice. The aim of this small scale pilot study is to evaluate this hypothesis.  
 
 
1.2 
RATIONALE FOR CURRENT STUDY 
 
Ivermectin is known to have a broad range of parasitic activities and is effective at treating many 
ectoparasitic infections. It is now considered the optimum drug for community treatment of scabies. The 
drug is also known to be effective for treating headlice but no studies have formally assessed whether 
community treatment for scabies also reduces headlice prevalence. This study will help us more fully 
understand any additional benefit on headlice when communities are treated for scabies 
 
 
 
 
 
 
 


IVM-LICE 
Page 8 of 26 
 Version 1.0 16/05/17 
 
2.  STUDY OBJECTIVES 
 
Study Aims: 
Assess the impact of a scabies treatment programme on the prevalence of head lice in the same 
community.  
 
 
Primary Objective: 
The primary objective is to see whether community treatment for scabies also reduces the prevalence of 
head lice. 


IVM-LICE 
Page 9 of 26 
 Version 1.0 16/05/17 
 
3.  STUDY DESIGN 
 
 
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.  
 
Study Site 
This study will be conducted on the campus of Atoifi Adventist Hospital. All staff and their families living 
on the campus will be invited to participate. Based on input from collaborators at Atoifi campus it is 
recognised that headlice is a common problem particularly amongst children living on the hospital 
campus. Treatment will be provided at the level of the community in line with recommendations and best 
evidence for scabies. All individuals on the campus will be offered treatment and will be invited to 
participate in the study. 
  
Treatment will be provided at the level of the community in line with recommendations and best evidence 
for scabies. All individuals will be invited to participate in the study and will be offered treatment. 
 
Community Awareness 
Prior to the study commencing we will engage community leaders on at the hospital campus.  A research 
training workshop will be held at AAH and which will be attended by AAH and other study staff as well as 
key community leaders. This meeting will provide an opportunity for explanation of the study aims and 
methodologies and for study staff to answer questions about the study design and implementation. 
 
Eligibility Criteria: 
All residents of the Atoifi Hospital campus will be invited to participate in the study. 
 
Inclusion Criteria: 
All residents of the selected communities will be invited to participate in the study. 
 
Exclusion Criteria: 
Individuals with a contra-indication to treatment. 
Individuals not consenting to participate. 
 
 
 
 
 
 


IVM-LICE 
Page 10 of 26 
 Version 1.0 16/05/17 
 
Duration 
The duration of the study is 3 months. For all participants, there will be a 15 day on-study period 
which will include two visits by the study team  
• 
Day 1 for baseline medical assessment and delivery treatment  
• 
Day 8-15 for delivery of second dose of treatment 
 
Treatment 
 
No investigational medications or indications are being assessed. All individuals will receive standard 
treatment for scabies.  
 
Treatment of scabies: 
• 
Day 1 for baseline medical assessment and delivery of ivermectin (or permethrin  & malathion 
when contra-indicated) 
• 
Day 8 for delivery of second dose of ivermectin 
An oral dose of Ivermectin (200μg/kg). 
 
In individuals with a contra-indication (pregnancy, breast-feeding, weight <15kg) permethrin cream and 
malathion shampoo will be offered instead. 
 


IVM-LICE 
Page 11 of 26 
 Version 1.0 16/05/17 
 
3.1 
STUDY OUTCOME MEASURES 
 
 
Primary Outcome 
a) Change in prevalence of headlice between baseline and follow-up 
 
Sample Size 
The required sample size was calculated to be 150 individuals based on the following assumptions. 
• Pre-treatment prevalence of headice of about 25% 
• Post-treatment prevalence of headlice of about 10% 
• Enrolment 80%  
 
Data and all appropriate documentation will be stored for a minimum of 5 years after the completion 
of the study, including the follow-up period.   
 
 
3.2 
RISKS AND BENEFITS 
 
The safety profile of ivermectin is very well known. Safety has been well studied through its usage 
therapeutically and in large scale MDA programs. In the past 21 years, more than 1 billion doses of 
ivermectin tablets have been distributed for both onchocerciasis and lymphatic filariasis. Several 
studies of  pregnant women accidentally given ivermectin showed no evidence of teratogenicity[4–6].  
Participants will benefit from receiving treatment for scabies and headlice as part of the study. These are 
both major public health problems in the Solomon Islands and participants will therefore gain benefit 
from receiving the best available treatment for these conditions which, it is believed, will result in 
improvements in their health and well being. 
 
Benefits to Communities 
Communities will benefit from receiving treatment for scabies as part of these studies. This is a major 
public health problems in the Solomon Islands and participants will therefore gain benefit from receiving 
the best available treatment for this condition which, it is believed, will result in improvements in their 
health and well being. 
 
Blinding 
This is an open-label study 


IVM-LICE 
Page 12 of 26 
 Version 1.0 16/05/17 
 
4. 
SELECTION AND WITHDRAWAL OF PARTICIPANTS  
 
4.1 
PRE-TREATMENT EVALUATIONS  
Treatment of the whole community with Ivermectin and Permethrin is the best available treatment 
for the purpose of scabies control.  Individual treatment results in re-infestation and treatment 
failure. In line with recommendation therefore treatments is offered to all individuals regardless of 
the presence/absence of clinical features of either disease. 
 
 
4.2 
INCLUSION CRITERIA 
All consenting individuals in the participating communities will be eligible to participate 
 
4.3 
EXCLUSION CRITERIA. 
Individuals not consenting to participate in the study. 
Individuals who are unwell on the day that study medications are administered. 
 
 
4.4 
WITHDRAWAL CRITERIA 
Study participation is voluntary and study participants can withdraw at any time. The number of 
withdrawals will be recorded and only data collected prior to withdrawal will be included in the 
analysis.  Only data collected prior to withdrawal will be included in the analysis.   
 
 


IVM-LICE 
Page 13 of 26 
 Version 1.0 16/05/17 
 
 
5. 
TRIAL MEDICATION  
 
5.1 
Name and description of investigational medicinal product(s) 
 
No investigational treatments are being tried. Ivermectin  (and permethrin) is a recognised treatment for 
scabies and is on the Solomon Islands Essential Drug List for this indication. 
 
Ivermectin  
Ivermectin is an anthelminthic. Ivermectin is metabolized in the liver, and ivermectin and/or its 
metabolites are excreted almost exclusively in the feces over an estimated 12 days, with less than 1% 
of the administered dose excreted in the urine. After oral administration, the apparent plasma half- 
life of ivermectin is approximately 16 hours. Ivermectin is indicated for the treatment of 
onchocerciasis or river blindness caused by Onchocerca volvulus and for strongyloidiasis caused by 
Strongyloides stercoralis. The recommended dosage for treatment of scabies is two oral doses 
designed to provide approximately 200μg of ivermectin per kg of body weight. The same dose is 
recommended in the Solomon Islands. Ivermectin is available in 3mg tablets.  
Topical 5% permethrin cream (Lyclear®)  
Topical 5% permethrin (Lyclear ®) cream for scabies is supplied in a 30g tube. The cream is applied 
all over the body including from neck to toe and washed off after a minimum of 8 hrs. For children 
aged 2 months or less permethrin should be washed off after 4 hours.  
 
5.2 
Legal status of drug 
 
Permethrin is licenced in the UK for the treatment of scabies. It is listed as on the essential medicines 
list for the Solomon Islands and recommended as a potential treatment for scabies. 
 
Ivermectin is not licenced for the treatment of scabies in the UK although NICE has provided guidance 
on its use (https://www.nice.org.uk/advice/esuom29/resources/ivermectin-for-difficulttotreat-
scabies-17546902981). Ivermectin is widely used in control programmes for both Onchocerciasis 
and Lymphatic Filariasis.   Ivermectin is listed as on the essential medicines list for the Solomon 
Islands and recommended as a potential treatment for scabies.  
 
 
5.4 
Drug Storage and Supply 
Medications will arrive by plane and will reach the islands by boat at the provincial pharmacy / 
medical store. The order request will be checked with the supplies delivered. The delivery notice 
number, delivery date and the medications batch number will be recorded in a log book. Medications 


IVM-LICE 
Page 14 of 26 
 Version 1.0 16/05/17 
will be taken out of the pharmacy in bulk by the study teams for dispensing in the community. Study 
teams will maintain a log of all medicines dispensed that can be cross-checked against participants 
study records.  
 
 
 
 
 
 
 
 
 
 
5.5 
Preparation and labelling of IMP 
For 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 
Dosage schedules/modifications 
In line with standard treatment the dosing of Ivermectin will use the following weight bands 
 
 
Permethrin will be used instead of Ivermecitn in the following circumstances 
• 
Pregnancy 
• 
Breastfeeding 
• 
Child <6 months age 
• 
Child <15kg 
 
Where permethrin is indicated the following standard dosing protocol will be used: 
• 
Full tube for adults. 
• 
Half tube for children. 
• 
Apply to whole body and leave on for 1 day before washing off 
 
 
5.7 
Known drug reactions and interaction with other therapies 
 
WEIGHT 
IVERMECTIN 
TABLETS 
(3mg Tabs) 
<15KG 
PERMETHRIN 
CREAM 
15KG 
1 
25 – 37.5 KG 
2 
37.5 – 50 KG 
3 


IVM-LICE 
Page 15 of 26 
 Version 1.0 16/05/17 
The safety profile of ivermectin is well 
established from large mass treatment 
campaigns where >100 million doses have been administered. The most commonly reported side 
effects are for Ivermectin are headache, dizziness, itch. Adverse events are normally mild and self-
limiting with no specific therapy required. Permethrin does not commonly cause any systemic 
adverse commons. 
 
 
 
5.8 
Concomitant medication 
Individuals receiving Warfarin may not receive treatment with Ivermectin due to potential 
interactions. No individuals outside of the capital of the Solomon Islands (Honiara) are receiving 
Warfarin due to a lack of INR monitoring facilities and therefore it is not anticipated that any 
individuals in the study will be receiving a contra-indicated concomitant medication. Permethrin will 
be offered if a patient taking warfarin was identified. 
 
5.9 
Trial restrictions 
There are no trial restrictions.  
As noted above pregnant and breast feeding women and children <15kg will be offered permethrin 
rather than ivermectin but will still be allowed to participate in the study. 
 
5.10 
Assessment of compliance 
Drugs will be delivered as a single observed treatment and therefore compliance will be assessed at 
the time of drug distribution. 
 
 
50-75 KG 
4 
>75 KG 
5 


IVM-LICE 
Page 16 of 26 
 Version 1.0 16/05/17 
 
6. 
SAFETY REPORTING FOR DRUG TRIALS  
 
6.1 
DEFINITIONS   
 
Term 
Definition 
Adverse 
Event 
(AE) 
Any untoward medical occurrence in a participant to whom a medicinal product 
has been administered, including occurrences which are not necessarily caused 
by or related to that product. 
 
An AE can therefore be any unfavourable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with 
the use of an investigational medicinal product (IMP), whether or not considered 
related to the IMP. 
Adverse Reaction 
(AR) 
Any untoward and unintended response in a participant to an investigational 
medicinal product which is related to any dose administered to that participant. 
 
The phrase “response to an investigational medicinal product” means that a 
causal relationship between a trial medication and an AE is at least a reasonable 
possibility, i.e. the relationship cannot be ruled out. 
 
All cases judged by either the reporting medically qualified professional or the 
Sponsor as having a reasonable suspected causal relationship to the trial 
medication qualify as adverse reactions. 
Serious 
Adverse 
Event (SAE) 
A serious adverse event is any untoward medical occurrence that: 
• Results in death 
• Is life-threatening 
• Requires inpatient hospitalisation or prolongation of existing hospitalisation 
• Results in persistent or significant disability/incapacity 
• Consists of a congenital anomaly or birth defect 
 
Other ‘important medical events’ may also be considered serious if they 
jeopardise the participant or require an intervention to prevent one of the above 
consequences.   
 
Serious 
Adverse 
Reaction (SAR) 
An adverse event that is both serious and, in the opinion of the reporting 
investigator, believed with reasonable probability to be due to one of the trial 
treatments, based on the information provided. 
Suspected 
Unexpected 
Serious 
Adverse 
Reaction (SUSAR) 
A serious adverse reaction, the nature and severity of which is not consistent 
with the information about the medicinal product in question set out: 
 
• In the case of a product with a marketing authorisation, in the summary of 
product characteristics (SmPC) for that product 
• In the case of any other investigational medicinal product, in the investigator 
brochure (IB) relating to the trial in question. 
 
6.2 
CAUSALITY 
Most adverse events and adverse drug reactions that occur in this study, whether they are serious or not, 
will be expected treatment-related side effects due to the drugs used in this study.  The assignment of  
causality should be made by the investigator responsible for the care of the participant using the 
definitions in the table below. 
 
If any doubt about the causality exists the local investigator should inform the study coordination centre 
who will notify the Chief Investigators.  The pharmaceutical companies and/or other clinicians may be 
asked to advise in some cases. 
 


IVM-LICE 
Page 17 of 26 
 Version 1.0 16/05/17 
In the case of discrepant views on causality between the investigator and others, all parties will discuss 
the case.  In the event that no agreement is made, both points of view are to be reported.  
 
Relationship 
Description 
Unrelated 
There is no evidence of any causal relationship 
Unlikely 
There is little evidence to suggest there is a causal relationship (e.g. the event did 
not occur within a reasonable time after administration of the trial medication).  
There is another reasonable explanation for the event (e.g. the participant’s 
clinical condition, other concomitant treatment). 
Possible 
There is some evidence to suggest a causal relationship (e.g. because the event 
occurs within a reasonable time after administration of the trial medication).  
However, the influence of other factors may have contributed to the event (e.g. the 
participant’s clinical condition, other concomitant treatments). 
Probable 
There is evidence to suggest a causal relationship and the influence of other 
factors is unlikely. 
Definitely 
There is clear evidence to suggest a causal relationship and other possible 
contributing factors can be ruled out. 
Not assessable 
There is insufficient or incomplete evidence to make a clinical judgement of the 
causal relationship. 
 
6.3 
REPORTING PROCEDURES 
Depending on the nature of the event the reporting procedures below should be followed.  Any questions 
concerning adverse event reporting should be directed to the study coordination centre in the first 
instance.   
 
6.3.1 Non serious Adverse Reactions (ARs)/Adverse Events (AEs) 
Given the established safety profile of the drugs being used in this study and the fact that they are being 
used for established indications we will only collect data on SAEs and SUSARs. 
 
 
6.3.2 Serious Adverse Reactions (SARs)/Serious Adverse Events (SAEs) 
Serious Adverse Events (SAEs) and Serious Adverse Reactions (SARs) should be reported to the study 
coordination centre within 24 hours of the local site being made aware of the event.   
 
An SAE form should be completed and submitted to the study coordination centre with as much detail of 
the event that is available at that time.  If awaiting further details, a follow up SAE report should be 
submitted promptly upon receipt of any outstanding information.  The CI (for a single-centre trial) or PI 
(for a multi-centre trial) must record the event with an assessment of seriousness, causality and 
expectedness. 
 
Any events relating to a pre-existing condition or any planned hospitalisations for elective treatment of a 
pre-existing condition do not need reporting as SAEs. 
 
 
6.3.3 SUSARs  
 
All SAEs assigned by the PI or delegate as both suspected to be related to IMP-treatment and unexpected 
will be classified as SUSARs and will be subject to expedited reporting to the Regulatory Authority, in the 
UK: Medicines and Healthcare Products Regulatory Agency (MHRA).  The Sponsor (or delegate) will 
inform the MHRA, and the ethics committee of UK-relevant SUSARs within the required expedited 
reporting timescales (as per LSHTM Standard Operating Procedure for recording, managing and reporting 
of adverse events for IMP studies). 
 
For blinded trials, all SUSARs must be reported assuming the active compound is involved.   
 
 
In the case of a suspected, unexpected, serious adverse reactions (SUSAR), the staff at the site should:  


IVM-LICE 
Page 18 of 26 
 Version 1.0 16/05/17 
 
1. Contact the study coordination centre immediately by phone or email to inform them of the event.   
2. Submit a completed SAE form (signed and dated) within 24 hours, together with relevant 
treatment forms and anonymised copies of all relevant investigations. 
3. Submit any additional information promptly upon request.   
 
 
Contact details for reporting SAEs and SUSARs 
Telephone: +677 7738438 / +44 7984 643424 
Email: michael.marks@lshtm.ac.uk 
 
 
 
 
 


IVM-LICE 
Page 19 of 26 
 Version 1.0 16/05/17 
 
7. 
ASSESSMENT AND FOLLOW-UP  
 
Data Collection 
At baseline all individuals will undergo a standardized examination to collect data on the presence of 
scabies, impetigo and headlice.  Following examination individuals will be weighed and directly observed 
treatment will be dispensed in line with standard treatment guidelines (see below). Individuals will be re-
examined at 48 hours to assess immediate killing of head-lice, again at 2 weeks and 3 months.   
No samples are collected as part of this study 
 
7.1 LOSS TO FOLLOW-UP 
This is not an individually randomised clinical trial but allowance has been made for loss to follow-up in 
the sample size calculation. 
 
7.2TRIAL COMPLETION 
The trial is planned to run over a 3 month period. The trial will be complete at the end of this 3 month 
period.   
 
 


IVM-LICE 
Page 20 of 26 
 Version 1.0 16/05/17 
 
8. 
STATISTICS AND DATA ANALYSIS 
 
Sample Size 
The required sample size was calculated to be 150 individuals based on the following assumptions. 
• Pre-treatment prevalence of headice of about 25% 
• Post-treatment prevalence of headlice of about 10% 
• Enrolment 80%  
 
Primary Outcome 
a) Change in prevalence of headlice between baseline and follow-up 
 
Data and all appropriate documentation will be stored for a minimum of 10 years after the 
completion of the study, including the follow-up period.   
 
 


IVM-LICE 
Page 21 of 26 
 Version 1.0 16/05/17 
 
9. MONITORING 
 
9.1 RISK ASSESSMENT 
This is considered a low risk study. 
All the drugs being used are being prescribed for routine indications and have well established safety 
profiles. As such only passive monitoring for adverse events will be undertaken during the study.  
 
9.2 MONITORING AT STUDY COORDINATION CENTRE 
Data will be entered directly into an electronic database at the time of the study. Consent forms will 
be reviewed to ensure completion in line with GCP standards. 
 
9.3 MONITORING AT LOCAL SITE 
Site visits will take place at D1 (treatment scabies), D8 (second treatment for scabies) and month 3 
(assessment of outcome).  A random selection of consent forms and data collection forms will be 
reviewed at the baseline visits and adverse event and data collection forms at each subsequent visit.  
 


IVM-LICE 
Page 22 of 26 
 Version 1.0 16/05/17 
 
 
10. 
REGULATORY ISSUES 
 
10.1 
ETHICS APPROVAL 
 
The Study Coordination Centre has applied for ethics approval from the LSHTM Research Ethics 
Committee, as well as the Solomon Islands National Ethics Board and the Atoifi Adventist Hospital Ethics 
Committee. 
 
Substantial protocol amendments will not be implemented until a favourable opinion has been granted 
from both the ethics committee. Correspondence from both ethics committees will be maintained in the 
trial master file. As the duration of the study is 3 months the annual progress report will accompany the 
notification of the end of the study.  
 
 
10.2 
CONSENT AND CONFIDENTIALITY 
 
Prior to performing any study specific procedure, written informed consent will be obtained for each 
subject. Information sheets explaining the study will be distributed to community nurses who will be 
trained in explaining the study. For subjects below the legal age, a parent or legal guardian must provide 
consent. Written consent will be obtained in local dialect on all occasions.   
 
10.3 
Confidentiality 
All data will be fully-anonymised. A copy of the database will be held both at Atoifi Hospital and LSHTM. 
The study database will not contain any patient identifiable information. Forms will be retained at Atoifi 
Adventist Hospital. 
 
 
10.4 
INDEMNITY 
London School of Hygiene & Tropical Medicine holds Public Liability ("negligent harm") and Clinical Trial 
("non-negligent harm") insurance policies which apply to this trial. 
 
10.5 
SPONSOR 
London School of Hygiene & Tropical Medicine will act as the main sponsor for this study.  Delegated 
responsibilities will be assigned locally.   
 
10.6 
FUNDING 
This study is funded as part of a Wellcome Trust Research Fellowship held by Michael Marks.  
No payments will be made to patients participating in this study.  
 
10.7 
AUDITS AND INSPECTIONS  
The study may be subject audit by the London School of Hygiene & Tropical Medicine under their remit as 
sponsor, the Study Coordination Centre and other regulatory bodies to ensure adherence to GCP.  
 
 


IVM-LICE 
Page 23 of 26 
 Version 1.0 16/05/17 
 
11. 
TRIAL MANAGEMENT 
 
A Trial Management Group (TMG) will be appointed and will be responsible for overseeing the progress of 
the trial.  The day-to-day management of the trial will be co-ordinated by Michael Marks and Jason Diau.  
 
All treatments in the study are being given for standard indications and the drugs have known safety 
profiles including in the setting of co-administration. A DSMB will therefore not be appointed.  
 
All data will be held jointly by LSHTM and AAH. Data will be stored on an encrypted password protected 
server at both LSHTM and AAH.  
 
 


IVM-LICE 
Page 24 of 26 
 Version 1.0 16/05/17 
 
12. 
PUBLICATION POLICY 
 
All publications and presentations relating to the study will be authorised by the Trial Management Group.  
The first publication of the trial results will be in the name of the Trial Management Group, if this does not 
conflict with the journal’s policy.  If there are named authors, these will include at least the trial’s Chief 
Investigator, Statistician and Trial Coordinator.  Members of the TMG and the Data Monitoring Committee 
will be listed and contributors will be cited by name if published in a journal where this does not conflict 
with the journal’s policy.  Authorship of parallel studies initiated outside of the Trial Management Group 
will be according to the individuals involved in the project but must acknowledge the contribution of the 
Trial Management Group and the Study Coordination Centre. 
 


IVM-LICE 
Page 25 of 26 
 Version 1.0 16/05/17 
 
13. 
REFERENCES 
 
1  Marks M, Vahi V, Sokana O, et al. Mapping the Epidemiology of Yaws in the Solomon Islands: A Cluster 
Randomized Survey. Am J Trop Med Hyg 2015;92:129–33. doi:10.4269/ajtmh.14-0438 
2  International Association for the Prevention of Blindness. Trachoma Mapping in the Pacific. 2013.  
3  The World Health Organisation. Eradication of yaws - the Morges Strategy. Wkly Epidemiol Rec 
2012;87:189–94. 
4  Emerson PM, Burton MJ, Solomon AW, et al. The SAFE strategy for trachoma control: using 
operational research for policy, and implementation. Bull World Health Organ 2006;84:613–9. 
5  Sadiq ST, Glasgow KW, Drakely CJ, et al. Effects of azithromycin on malariometric indices in The 
Gambia. The Lancet 1995;346:881–2. doi:10.1016/S0140-6736(95)92712-3 
6  Keenan JD, Ayele B, Gebre T, et al. Childhood Mortality in a Cohort Treated With Mass Azithromycin 
for Trachoma. Clin Infect Dis 2011;52:883–8. doi:10.1093/cid/cir069 
7  Coles CL, Mabula K, Seidman JC, et al. Mass distribution of azithromycin for trachoma control is 
associated with increased risk of azithromycin-resistant Streptococcus pneumoniae carriage in young 
children 6 months after treatment. Clin Infect Dis Off Publ Infect Dis Soc Am 2013;56:1519–26. 
doi:10.1093/cid/cit137 
8  Romani L, Steer AC, Whitfeld MJ, et al. Prevalence of scabies and impetigo worldwide: a systematic 
review. Lancet Infect Dis 2015;15:960–7. doi:10.1016/S1473-3099(15)00132-2 
9  Heukelbach J, Feldmeier H. Scabies. The Lancet 2006;367:1767–74. doi:10.1016/S0140-
6736(06)68772-2 
10  Romani L, Whitfeld MJ, Koroivueta J, et al. Mass Drug Administration for Scabies Control in a 
Population with Endemic Disease. N Engl J Med 2015;373:2305–13. doi:10.1056/NEJMoa1500987 
11  Marks M, Vahi V, Sokana O, et al. Impact of Community Mass Treatment with Azithromycin for 
Trachoma Elimination on the Prevalence of Yaws. PLoS Negl Trop Dis 2015;9:e0003988. 
doi:10.1371/journal.pntd.0003988 
12  Mitjà O, Houinei W, Moses P, et al. Mass Treatment with Single-Dose Azithromycin for Yaws. N Engl J 
Med 2015;372:703–10. doi:10.1056/NEJMoa1408586 
13  Taplin D, Porcelain SL, Meinking TL, et al. Community control of scabies: a model based on use of 
permethrin cream. Lancet 1991;337:1016–8. 
14  Chippaux JP, Gardon-Wendel N, Gardon J, et al. Absence of any adverse effect of inadvertent 
ivermectin treatment during pregnancy. Trans R Soc Trop Med Hyg 1993;87:318. 
15  Gyapong JO, Chinbuah MA, Gyapong M. Inadvertent exposure of pregnant women to ivermectin and 
albendazole during mass drug administration for lymphatic filariasis. Trop Med Int Health TM IH 
2003;8:1093–101. 
16  Pacqué M, Muñoz B, Poetschke G, et al. Pregnancy outcome after inadvertent ivermectin treatment 
during community-based distribution. Lancet Lond Engl 1990;336:1486–9. 
17  Coulibaly YI, Dicko I, Keita M, et al. A cluster randomized study of the safety of integrated treatment of 
trachoma and lymphatic filariasis in children and adults in Sikasso, Mali. PLoS Negl Trop Dis 
2013;7:e2221. doi:10.1371/journal.pntd.0002221 
 


IVM-LICE 
Page 26 of 26 
 Version 1.0 16/05/17