Condition category
Digestive System
Date applied
23/08/2019
Date assigned
05/09/2019
Last edited
04/09/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Schistosomes are worm infections that can cause liver damage. We have seen evidence of this liver damage in children in Hoima District. Currently your community is provided with the drug praziquantel (biltricide tablets) once per year through the national treatment programme known as MDA. We have found liver damage due to schistosomes to be very common in your district despite the MDA programme. As praziquantel (biltricide tablets) is the only treatment available for schistosomes, we want to see if treating children more than once a year reduces the amount of liver damage seen. We want to find out if increasing the amount of praziquantel (biltricide tablets) given to children reduces their worm infections (Schistosomes) and liver disease.

Who can participate?
Children aged 6-14 can participate in the trial. We plan to include 600 participants from primary schools in Hoima District. Participation in this trial is completely voluntary.

Your child may not participate in the trial if they have had swelling of the face or neck following previous treatment with praziquantel (biltricide tablets) and have lived in the local area for less than two years.

What does the study involve?
The trial involves comparing three different praziquantel (biltricide tablets) treatment plans. Your child will be allocated to one of the treatments for this trial in a random way (by chance). Your child will have an equal chance of receiving praziquantel (biltricide tablets) once, twice or four times a year. For each treatment, children will receive praziquantel (biltricide tablets) following the procedure used by the Uganda Department of Health during school-treatment days. The amount of praziquantel (biltricide tablets) to be received by a child will be determined by their height. A teacher who is trained to treat the children will provide the praziquantel tablets, which the children are to swallow. A member of the study team will observe the treatment to ensure that it is conducted properly.

Prior to receiving praziquantel (biltricide tablets) we will carry out an ultrasound examination, which uses sound waves to create an image of your child’s liver. It will not cause any discomfort. Your child will be asked to provide three stool samples and one urine sample. These samples will be used to determine how many schistosomes (worms) your child is infected with. We will also collect parasites from these samples to examine the parasites’ genetic code. Three more stool samples and one urine sample will be collected four-weeks after treatment, to see how successful the drug has been, and what schistosome worms and parasites survived. An 8ml blood sample, equivalent to one and a half teaspoons, will be collected from your child. This blood sample will be used to measure how your child’s body responds to the parasite. We will relate what we measure in blood samples to the children’s liver images. Collecting blood can sometimes cause bruising.

The trial will last two years. The assessments will be repeated once a year. In total your child will provide 18 stool samples, 6 urine samples and 3 blood samples of 8ml.

All information collected about your child as a result of their participation in the trial will be kept strictly confidential. The results will be anonymous and your child will not be identifiable from any of the data produced. Anonymous datasets from the trial will be made available to other researchers. We will report the overall results to your community. Once the trial has finished, the once per year provision of praziquantel (biltricide tablets) will continue through the national treatment programme (MDA).

What are the possible benefits and risks of participating?
There is no guarantee that your child will benefit from taking part in this trial. They may experience improvement in their disease. However, information collected as part of their participation may be used by the Ugandan Government to improve schistosome treatment programmes in the future. You will not receive any payment for your child participating in this trial but we will compensate the school time missed through your child’s participation in this trial. This will be through the provision of school stationery.

Praziquantel (biltricide tablets) have been used for many years and its side-effects are well known. The risks that a single dose of praziquantel can have are mild and short-lived side effects. Headaches and abdominal pain, with or without nausea or vomiting, are very common. Dizziness, drowsiness, a rash and diarrhoea are common.

In very rare cases, intense itchy skin or swelling of the lips and tongue have been reported. In the very unlikely event that your child experiences either of these or your child is feeling very unwell, please contact your trial manager immediately. Their number will be given to you in a patient information sheet before the start of treatment.

As praziquantel (biltricide tablets) passes through the body quickly, with any drug left after killing of the worms passed in the urine within 2 days after treatment, the increased doses in two of the treatment groups should not make these effects or risks worse. To help reduce the side effects we will provide your child with food prior to treating them with praziquantel (biltricide tablets).

Where is the study run from?
The trial is run and managed by the Vector Control Division – Ministry of Health, Uganda in collaboration with Makerere University, University of Cambridge, and Cambridge University Hospitals Trust.

When is the study starting and how long is it expected to run for?
The trial is planned to open to recruitment in October 2019 and is expected to run for two years and two months.

Who is funding the study?
The trial is funded by the European and Developing Countries Clinical Trials Partnership Programme (EDCTP).

Who is the main contact?
James Ssenfuka
jasenfuka@yahoo.com

Trial website

Contact information

Type

Public

Primary contact

Dr Katrina Gatley

ORCID ID

http://orcid.org/0000-0003-2622-1373

Contact details

Cambridge Clinical Trials Unit
Box 401
Cambridge University Hospitals NHS Foundation Trust
Addenbrooke's Hospital Level 6
Coton House
Hills Road
Cambridge
CB2 0QQ
United Kingdom
+44(0)1223 216740
katrina.gatley@addenbrookes.nhs.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

CCTU0255

Study information

Scientific title

Impact of increased praziquantel frequency on childhood fibrosis in persistent schistosomiasis morbidity hotspots. A phase IV CTIMP trial

Acronym

FibroScHot

Study hypothesis

Increasing praziquantel treatment frequency will be an effective disease control strategy in hotspots of schistosomiasis morbidity.

Ethics approval

1. Approved 10/06/2019, Vector Control Division Research Ethics Committee (15 Bombo Road Kampala Uganda; 256-414-253407; vcdmohrec@gmail.com), Rec Ref: UG-REC-018; PI Ref: VCDREC/110.
2. Approved 10/06/2019, Makerere University Research Ethics Committee (PO Box 7062, Kampala, Uganda; 256-41-545040; makssrec@gmail.com), REC Ref: MAKSS REC 05.19.297; PI Ref: MAKSS REC 04.19.283.
3. Approved 09/04/2019, University of Cambridge, Human Biology Research Ethics Committee (17 Mill Lane, Cambridge, CB2 1RX, UK; 44-223 766894; cb480@admin.cam.ac.uk), ref: HBREC.2018.32.

Study design

Phase IV, single centre, randomised, open label trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Schools

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet.

Condition

Periportal fibrosis of the liver caused by schistsosomiasis mansoni

Intervention

This trial is designed to align with the national Uganda Neglected Tropical Disease Control Programme, Mass Drug Administration with Praziquantel, (MDA) which is a public health programme. The public health programme is delivered annually through the primary schools and the control arm for this trial mimics the annual public health programme.

The IMP is Praziquantel, the dose is ~40mg/kg, dependent on standardised and verified dose pole. This is the method used to determine dose for the MDA. Maximum dose 5x600mg tablets. The IMP is given orally after food. Children who are treated with praziquantel will be directly observed for 1-hour with follow-up the next day. Total treatments detailed below include an end of trial final treatment. The trial runs over 50 months: the treatment period over two years.

Randomisation will be stratified by school. Individuals will be randomised on a 1:1:1 ratio into the control or intervention arms. Six hundred primary school-aged children will be enrolled in the study and 200 randomised into each of the three arms.

Assessments during the trail:
2 x 3 day-annual screening period for S. mansoni egg counts and ultrasonography examination. The Ultrasound Examination and the collection of stool samples will be collected up-to 2-weeks prior to treatment with praziquantel.
3 x 3 day-annual 4-week follow up screen for S. mansoni egg counts. Stool samples will be collected at 4-weeks post treatment to assess treatment efficacy.

Intervention period:
Control arm: 3 treatments of Praziquantel, provided annually.
Intervention arm 1: 5 treatments, provided bi-annually at ~6 months apart
Intervention arm 2: 9 treatments, provided quarterly at ~3 months apart.
Timings of treatments are shown in the Schedule of Assessments. Their exact timing is dependent on the timings of the Ugandan school-terms for that year.

Follow-up period:
Outcome assessments will be conducted two years after the first annual treatment of individuals in all arms of the study (Ultrasound Examination and the collection of stool samples). The assessments will be conducted over 3-days for each individual.

Intervention type

Drug

Phase

Phase IV

Drug names

Praziquantel

Primary outcome measure

Prevalence of periportal fibrosis, defined as Niamey Protocol pattern scores of C,D,E or F, measured at 2-years follow-up.

Secondary outcome measures

Schistosoma mansoni infection intensities are measured using Kato-Katz faecal egg counts (28) at 2-years follow-up.

Overall trial start date

01/08/2018

Overall trial end date

01/10/2022

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Have a parent/guardian who has given written/marked informed consent for the child to participate.
2. Given written/marked informed assent to participate.
3. Aged 6-14 years of age.
4. Born or resident within the community in which their school is situated for >=2 years.

Participant type

Other

Age group

Child

Gender

Both

Target number of participants

600

Participant exclusion criteria

History of facial oedema after treatment with praziquantel

Recruitment start date

01/10/2019

Recruitment end date

01/12/2019

Locations

Countries of recruitment

Portugal, Uruguay

Trial participating centre

School of Public Health, Makerere University
New Mulago Hill Road
Kampala
UG
Uganda

Sponsor information

Organisation

Cambridge University Hospital Trust

Sponsor details

Box 277
1 Hills Road
Cambridge
CB2 0QQ
United Kingdom
+44(0)1223 596474
cctu@addenbrookes.nhs.uk

Sponsor type

Hospital/treatment centre

Website

www.cuh.org.uk/cctu

Organisation

The Chancellor, Masters and Scholars of the University of Cambridge

Sponsor details

The Old Schools
Trinity Lane
Cambridge
CB1 1TS
United Kingdom
01223 766362
Jo.Dekkers@admin.cam.ac.uk

Sponsor type

University/education

Website

www.research-operations.admin.cam.ac.uk

Funders

Funder type

Government

Funder name

European and Developing Countries Clinical Trials Partnership

Alternative name(s)

EDCTP

Funding Body Type

private sector organisation

Funding Body Subtype

international

Location

Netherlands

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal. The investigators and sponsors commit to the timely publication of the clinical trial results in accordance with the WHO and funders joint statement on public disclosure of results from clinical trials http:// www.who.int/ictrp/results/jointstatement/en/. Summary results of the trial will be made available by posting to the results section of the clinical trial registry and by journal publication. A timeframe of 6 months from release of key statistics is given for provision of the clinical report to Merck KGaA, and 12 months from primary study completion (the last visit of the last subject for collection of data on the primary outcome) will be the expected timeline for posting of summary results in the clinical trial registry, with an indicative timeline of 24 months from study completion for publication in a journal.

IPD sharing statement: a proportion of the dataset will be made available to open archiving platforms as per ‘Pilot on Open Research Data in Horizon 2020’ commitments, specific of which will be decided at a later date.

Intention to publish date

01/11/2023

Participant level data

Stored in repository

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

04/09/2019: Trial's existence confirmed by the University of Cambridge, Human Biology Research Ethics Committee, the Makerere University Research Ethics Committee and the Vector Control Division Research Ethics Committee.