ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12617000738325

Ethics application status

Approved

Date submitted

11/05/2017

Date registered

22/05/2017

Date last updated

20/01/2020

Date data sharing statement initially provided

15/02/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

Fiji Integrated Therapy (FIT) - Triple therapy for lymphatic filariasis, scabies and soil transmitted helminths in Fiji

Scientific title

Community Based Safety Study of 2-drug (Diethylcarbamazine and Albendazole) versus 3-drug (Ivermectin, Diethylcarbamazine and Albendazole) Therapy for Lymphatic Filariasis, Scabies and Soil Transmitted Helminths in Fiji

Secondary ID [1]

None

Universal Trial Number (UTN)

Trial acronym

FIT

Linked study record

NCT02899936
CTRI/2016/10/007399

Health condition

Health condition(s) or problem(s) studied:

lymphatic filariasis (LF)

scabies

impetigo

soil transmitted helminths (STH)

Condition category

Condition code

Infection

Other infectious diseases

Public Health

Other public health

Skin

Dermatological conditions

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

IDA1 Arm:
- ivermectin, diethylcarbamazine and albendazole Day 0,
- permethrin Day 0 if excluded from ivermectin
IDA2 Arm:
- ivermectin, diethylcarbamazine and albendazole Day 0, ivermectin Day 8
- permethrin Day 0 and Day 8 if excluded from ivermectin

Details of dosing:
- ivermectin: 200 mcg/kg oral
- diethylcarbazine: 6mg/kg oral
- albendazole 400mg oral
- permethrin 5% cream topical: apply to whole body and wash off after 4hrs when less than 2 months; apply to whole body and wash off after 8hrs when 2 months and older.

Directly observed therapy (DOT) will be used for ivermectin, diethylcarbamazine and albendazole.
Instructions will be provided for application of permethrin cream when distributed but application will not be observed, since this is normally done at night to avoid inadvertent washing/rubbing off during daytime activities. Assistance by another person (household member/support person) will be required for application to ensure coverage of whole body.

Exclusion criteria for ivermectin, diethylcarbamazine and albendazole:
- severe illness (chronic renal insufficiency, severe chronic liver disease, or any illness that is severe enough to interfere with activities of daily living);
- allergy to ivermectin, diethylcarbamazine or albendazole;
- pregnant;
- breastfeeding within 7 days of delivery;
- less than 2 years old; OR
- less than 15 kg

In addition if less than 5 years old excluded from ivermectin.

Exclusion criteria for permethrin:
- allergy to permethrin
- crusted scabies

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

The control group will be the DA Arm. Villages randomised to this Arm will receive standard therapy for LF and scabies in Fiji.
DA Arm:
- diethylcarbamazine and albendazole Day 0
- permethrin Day 8 if scabies present in participant or household member
Details of dosing:
- diethylcarbazine: 6mg/kg oral
- albendazole 400mg oral
- permethrin 5% cream topical: apply to whole body and wash off after 4hrs when less than 2 months; apply to whole body and wash off after 8hrs when 2 months and older.

Directly observed therapy (DOT) will be used for diethylcarbamazine and albendazole.
Instructions will be provided for application of permethrin cream when distributed but application will not be observed, since this is normally done at night to avoid inadvertent washing/rubbing off during daytime activities. Assistance by another person (household member/support person) will be required for application to ensure coverage of whole body.

Exclusion criteria for diethylcarbamazine and albendazole:
- severe illness (chronic renal insufficiency, severe chronic liver disease, or any illness that is severe enough to interfere with activities of daily living);
- allergy to diethylcarbamazine or albendazole;
- pregnant;
- breastfeeding within 7 days of delivery;
- less than 2 years old; OR
- less than 15 kg

Exclusion criteria for permethrin:
- allergy to permethrin
- crusted scabies

Control group

Active

Outcomes

Primary outcome [1]

Determine the frequency, type, and severity of adverse events following triple drug therapy (IDA) compared to standard two drug therapy (DA) in LF infected and uninfected individuals in a community.

Participants will be interviewed and asked to report their general health status at baseline before receiving treatment and daily for the 2 days following treatment (Active Adverse Event Monitoring phase). For 3 to 7 days following treatment, anyone unwell the preceding day will be actively followed, other participants will be interviewed only if they feel unwell and present to the study team (Passive Adverse Event Monitoring phase).
At any stage if they describe being unwell, further questions to determine type and severity of symptom(s) experienced will be asked and recorded according to pre-defined adverse event table. If moderate to severe symptoms they will have further medical assessments as required.
The majority of adverse events expected are related to effective action of the medications on the parasites. Possible side effects include abdominal pain, nausea, vomiting, diarrhoea, fever, painful glands groin/neck/armpits, itch, swelling, headache, joint pain, fatigue, weakness, dizziness, fainting, racing heart or an allergic reaction (itchy rash, difficulty breathing, chest tightness and/or swelling face/tongue).

Methods of assessment:
LF infection status will be determined by Filiarial Test Strip (FTS) and microfilariae (mf) smears.
Adverse events - interviews +- medical assessment

Timepoint [1]

Community members will be actively followed daily for 2 days after treatment, and passively followed for period 3-7 days after treatment.

Secondary outcome [1]

To compare the efficacy of IDA to DA administered in communities for clearance of microfilariae (mf) and filarial antigenemia (composite outcome). Methods of assessment: FTS and Dried Blood Spot (DBS) for filarial antigenemia. mf smears and membrane filtration (24 month follow-up only) for microfilariae

Timepoint [1]

Baseline, 12 months and 24 months

Secondary outcome [2]

To assess the effect of intensity of filarial infection on the frequency and severity of adverse events.

Methods of assessment:
FTS and mf results
Documented adverse events

Timepoint [2]

FTS and mf results at baseline will be compared to documented adverse events monitored for 7 days following treatment.

Secondary outcome [3]

To evaluate the impact of IDA on scabies prevalence

Methods of assessment:
Skin examination

Timepoint [3]

Baseline and 12 months

Secondary outcome [4]

To evaluate the impact of IDA on STH (hookworm, ascaris, trichuris and strongyloides) prevalence

Methods of assessment:
Stool samples will be analysed using Kato-katz method, as well as PCR.

Timepoint [4]

Stool collected at baseline (pre-treatment), 4 weeks (individual response), and 12 months (community prevalence).

Secondary outcome [5]

To compare acceptability and feasibility of IDA to DA in communities at risk of LF, scabies and STH (composite outcome).

Methods of assessment:
Acceptability Survey, designed specifically for the Triple therapy studies
Focus group discussions
Interviews with key informants

Timepoint [5]

Approximately 4 weeks following treatment

Secondary outcome [6]

To evaluate the impact of IDA on impetigo prevalence.

Methods of assessment:
Skin examination

Timepoint [6]

Baseline and 12 months

Secondary outcome [7]

To evaluate the effect of 1 versus 2 doses of ivermectin on scabies prevalence.

Methods of assessment:
Skin examination

Timepoint [7]

Baseline and 12 months

Secondary outcome [8]

To evaluate the effect of 1 versus 2 doses of ivermectin on impetigo prevalence.

Methods of assessment:
Skin examination

Timepoint [8]

Baseline and 12 months

Eligibility

Key inclusion criteria

All community members will be invited to participate in the study

Minimum age

No limit

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

No informed consent

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Villages will be randomised by central computer.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Village randomisation - all participants in one village will be randomised to the same therapy. Randomisation will occur using a randomisation table created by computer software (i.e. computerised sequence generation).

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Phase 4

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

The total enrolment target of 4000 is based on total population of the two islands chosen for the study - Rotuma and Gau.
The de-identified data will be joined with data from other sites (Papua New Guinea, Haiti, India, Indonesia) to provide the numbers to evaluate the primary outcome.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

10/07/2017

Actual

13/07/2017

Date of last participant enrolment

Anticipated

27/10/2018

Actual

19/11/2018

Date of last data collection

Anticipated

24/10/2019

Actual

24/10/2019

Sample size

Target

4000

Accrual to date

Final

4773

Recruitment outside Australia

Country [1]

Fiji

State/province [1]

Rotuma and Gau islands in Eastern Division

Funding & Sponsors

Funding source category [1]

Other Collaborative groups

Name [1]

The Task Force for Global Health

Address [1]

325 Swanton Way,
Decatur, Georgia
30030

Country [1]

United States of America

Funding source category [2]

University

Name [2]

Death to Onchocerciasis and Lymphatic Filariasis (DOLF) Project, Washington University in St Louis

Address [2]

4444 Forest Park Avenue

St. Louis, Missouri 63108

Country [2]

United States of America

Primary sponsor type

Other Collaborative groups

Name

Murdoch Children's Research Institute

Address

Royal Children's Hospital
50 Flemington Rd
Parkville, Victoria
Australia 3052

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal Children's Hospital Melbourne Human Research Ethics Committee

Ethics committee address [1]

50 Flemington Rd, Parkville, Victoria, 3052

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

05/07/2016

Approval date [1]

12/09/2016

Ethics approval number [1]

36205

Ethics committee name [2]

Fiji National Health Research and Ethics Review Committee

Ethics committee address [2]

Dinem House, 88 Amy St, Toorak, Suva, Fiji

Ethics committee country [2]

Fiji

Date submitted for ethics approval [2]

11/07/2016

Approval date [2]

21/04/2017

Ethics approval number [2]

2016.81.MC

Summary

Brief summary

Lymphatic Filariasis (LF), scabies and soil transmitted helminths (STH) are common neglected tropical diseases affecting the people of Fiji. There is a dedicated LF eradication program supported by the World Health Organization (WHO), however scabies and STH are currently managed on an individual level with symptomatic treatment as required.
In an attempt to reduce the prevalence of LF globally, research is being undertaken into alternative, more effective treatment options. A recent study in Papua New Guinea demonstrated a new triple drug therapy (ivermectin, diethylcarbamazine and albendazole) is superior to the currently recommended two drug therapy (diethylcarbamazine and albendazole) used by WHO LF programs in the Pacific. However, adverse events were more frequent. Despite no serious adverse events being observed, it is necessary to conduct further studies to review the safety of this new triple therapy before it can be endorsed as an effective mass drug administration (MDA) regimen for LF in endemic countries. Fiji’s burden of LF, that has been recalcitrant to previous MDA with diethylcarbamazine and albendazole, make it an ideal site to obtain further efficacy and safety data of the triple therapy.
Ivermectin given to communities as MDA has been proven to be effective in reducing the community prevalence of scabies. What is not known is the effects of one dose versus two doses of ivermectin as MDA. This question will be reviewed within the design of the community randomised study. The prevalence of impetigo in a community is linked to scabies and this will also be reviewed.
Ivermectin and albendazole are both effective individually against STH. The effectiveness of this combination of treatment as MDA in Fiji for STH has not been studied. The effectiveness for the individual in the short-term and the community in the longer-term will be reviewed.
In addition, the acceptability and feasibility of the new therapy in communities at risk of these three diseases will be reviewed.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Andrew Steer

Address

Murdoch Children's Research Institute
Royal Children's Hospital
50 Flemington Rd, Parkville, Victoria, 3052

Country

Australia

Phone

+61393455522

Fax

andrew.steer@rch.org.au

Contact person for public queries

Name

Andrew Steer

Address

Murdoch Children's Research Institute
Royal Children's Hospital
50 Flemington Rd, Parkville, Victoria, 3052

Country

Australia

Phone

+61393455522

Fax

andrew.steer@rch.org.au

Contact person for scientific queries

Name

Andrew Steer

Address

Murdoch Children's Research Institute
Royal Children's Hospital
50 Flemington Rd, Parkville, Victoria, 3052

Country

Australia

Phone

+61393455522

Fax

andrew.steer@rch.org.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	The safety of combined triple drug therapy with ivermectin, diethylcarbamazine and albendazole in the neglected tropical diseases co-endemic setting of fiji: A cluster randomised trial.	2020	https://dx.doi.org/10.1371/journal.pntd.0008106
Embase	Community control strategies for scabies: A cluster randomised noninferiority trial.	2021	https://dx.doi.org/10.1371/journal.pmed.1003849
Embase	Individual Efficacy and Community Impact of Ivermectin, Diethylcarbamazine, and Albendazole Mass Drug Administration for Lymphatic Filariasis Control in Fiji: A Cluster Randomized Trial.	2021	https://dx.doi.org/10.1093/cid/ciab202

N.B. These documents automatically identified may not have been verified by the study sponsor.

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