Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001048178
Ethics application status
Approved
Date submitted
12/07/2019
Date registered
25/07/2019
Date last updated
25/07/2019
Date data sharing statement initially provided
25/07/2019
Date results provided
25/07/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
The effect of human mass praziquantel (PZQ) treatment, snail mollusciciding and bovine vaccination on the human incidence of schistosomiasis among individuals residing in endemic villages of the Philippines
Scientific title
The effect of human mass praziquantel (PZQ) treatment, snail mollusciciding and bovine vaccination on the human incidence of schistosomiasis among individuals residing in endemic villages of the Philippines
Secondary ID [1] 298720 0
APP1027265
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Schistosomiasis 313636 0
Condition category
Condition code
Infection 312063 312063 0 0
Studies of infection and infectious agents
Public Health 312091 312091 0 0
Other public health

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A five year phase III cluster randomised control trial was conducted among 18 schistosomiasis- endemic barangay comprising 18,221 residents in Northern Samar, The Philippines. We examined the impact of a combination of human mass chemotherapy, snail control through mollusciciding and SjCTPI bovine vaccination on the human incidence of infection. Following the baseline survey, the interventions were implemented in 18 intervention groups from 2013 to 2017. The investigators, including the research team, and study participants were blind to the vaccine allocation. At baseline all residents (60 mg/kg directly observed split oral dose) and bovines (30 mg/kg directly feed oral dose) were treated with a directly observed oral dose of PZQ. Villages were then pair-matched for the RCT based on historical prevalence, baseline outcomes, and transmission ecology. One of three intervention ARMs (no specific intervention (control), human mass praziquantel (PZQ) treatment, mollusciciding) were randomly assigned to each pair to achieve three pairs per intervention type. Within each pair, one village was randomly assigned the active vaccine for vaccinating bovines and the other village received a placebo vaccine. The intervention matrix is shown below:

Intervention---------Vaccinated Bovines-------Unvaccinated bovines

Mollusciciding----------3 Villages (A)----------------3 Villages (B)

Human treatment-----3 Villages (C)----------------3 Villages (C)

Neither------------------3 Villages (D)----------------3 Villages (e) Controls

Bovines received the priming SjCTPI DNA vaccine and then the protein boost or placebo control in VacSIM® six months later, in 2013 with subsequent booster vaccinations or placebo controls in VacSIM® given in 2014, 2015 and 2016. Full details of the production and formulation of the SjCTPI vaccines (plasmids encoding SjCTPI-HSP70 and UMVC3-mIL12 and recombinant SjCTPI), placebo control vaccine, the vaccination regimen, and the procedures for injecting bovines with the vaccine/placebo formulations have been provided (Da'Dara AA et al., Front Immunol. 2019 Feb 20;10:284. doi: 10.3389/fimmu.2019.00284. eCollection 2019) . VacSIM® was previously described (Grenfell RF et al., Clin. Vaccine Immunol. 2015 Mar 22(3):336-43). Human mass treatment with PZQ was carried out annually in the three randomly selected village pairs. Mollusciciding (following the annual snail surveys) was conducted in the three other randomly chosen pairs. Targeted snail ‘hotspots’ (areas close to human habitation with maximum or daily access to both human and bovines in an environment favored by snails), were sprayed with niclosamide (2 g/m2) annually.
Intervention code [1] 314983 0
Prevention
Intervention code [2] 315014 0
Treatment: Drugs
Comparator / control treatment
Human controls were treated at baseline and at scheduled follow-ups if found stool positive for schistosomiasis as per national and WHO guidelines. Annual human mass treatment was not conducted, village bovines were not vaccinated, and no mollusiciding spraying was conducted in the villages.
Control group
Active

Outcomes
Primary outcome [1] 320693 0
The primary outcome was the human incidence of schistosomiasis. Collection of a human stool sample, which was tested for S. japonicum infection using the Kato Katz (KK) thick smear technique in order to determine the incidence and infection intensity (Geometric Mean Eggs per Gram (GMEPG)).
Timepoint [1] 320693 0
Assessed at baseline and 1 year (primary endpoint), 2 years, 3 years and 4 years.
Secondary outcome [1] 372541 0
The secondary outcome was the human intensity of schistosomiasis infection. Collection of a human stool sample, which was tested for S. japonicum infection using the Kato Katz (KK) thick smear technique in order to determine infection intensity (Geometric Mean Eggs per Gram (GMEPG)).
Timepoint [1] 372541 0
Assessed at baseline and 1 year (primary endpoint), 2 years, 3 years and 4 years.

Eligibility
Key inclusion criteria
Individuals residing in endemic schistosomiasis villages in Norther Samar, the Philippines and expect to be living there for the next five years.
Minimum age
5 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Outside the designated age range (5-65 years) and/or do not plan to resident in the study area on the next five years.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation was not concealed.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Villages were matched into pairs (as closely as possible based on factors related to transmission: i.e. infection levels, transmission ecology and force of infection (e.g. water contact patterns, carabao to human numbers, sanitation practices, herding practices)) to reduce confounding and to increase statistical efficiency. Each pair was randomly allocated one of the intervention types (3), and then within each pair randomised into either vaccinated or unvaccinated bovines.
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
All data management and analyses used SAS (r) Proprietary Software 9.4 (TS1M2) (Copyright (c) 2002-2012 by SAS Institute Inc., Cary, NC, USA, Licensed to UNIVERSITY OF QUEENSLAND - EAS, Site 10005036). Data were double entered into a specially designed Microsoft Access-based database we developed; electronic copies of all entered data were saved offline and backup paper duplicates were stored in a secure location. Questionnaire survey data and results of the stool examinations were collected during the baseline survey in 2012-13 and at follow-ups from 2014 to 2017. Baseline and follow-up data for each village were cleaned and combined for the analyses in this paper. Based on intervention efficacy estimations (bovine vaccine efficacy 50%, human chemotherapy efficacy 85%, and targeted mollusciciding predicted efficacy 75%), an average infection rate of 10% in non-intervention villages, and a design effect (relating to paired differences) of 1.5, the study was proposed to have at least 90% power to detect the intervention effect. A SAS program was written to carry out the randomization to each intervention group. Analyses of human infection were restricted to those who satisfied the initial inclusion criteria and had baseline questionnaire and stool results and at least one follow-up stool result. Baseline infection prevalence and intensity were compared across intervention groups using logistic regression and normal regression (log-transformed EPG in those infected), respectively, with account taken of cluster effects within villages. The Nelson-Hsu adjustment for multiple comparisons was used to compare each of the nine intervention groups with the overall average. This approach was also used to compare bovine infection incidence within each year. For intervention assessment the primary outcome was human S. japonicum infection status at follow-ups in 2014, 2015, 2016 and 2017, with a positive infection defined as the presence of at least one egg on a KK slide. This was analyzed using a logistic regression model to compare interventions (grouped as control arm, human chemotherapy arm, mollusciciding arm, and vaccine group) over time, using a year-intervention group interaction. The models used GEEs to take account of clustering and repeated measures, with an unstructured correlation structure for the latter. The model included age group, sex and baseline infection as covariates. Contrasts were constructed to estimate the overall effect of each intervention (averaged over other intervention groups) for each follow-up year, and overall years. Subgroup effects were similarly estimated for the effect of each intervention within each other intervention group. Odds ratios and 95% confidence intervals were estimated.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
11/06/2012
Date of last participant enrolment
Anticipated
Actual
10/06/2013
Date of last data collection
Anticipated
Actual
27/11/2017
Sample size
Target
20000
Accrual to date
Final
18221
Recruitment outside Australia
Country [1] 21679 0
Philippines
State/province [1] 21679 0
Northern Samar

Funding & Sponsors
Funding source category [1] 303273 0
Government body
Name [1] 303273 0
National Health and Medical Research Council (NHMRC)
Country [1] 303273 0
Australia
Funding source category [2] 303275 0
Government body
Name [2] 303275 0
National Institutes of Health (NIH)
Country [2] 303275 0
United States of America
Primary sponsor type
University
Name
Griffith University
Address
Griffith University
Gold Coasts Campus
Parklands Drive
Southport, Qld
4215
Country
Australia
Secondary sponsor category [1] 303290 0
Government body
Name [1] 303290 0
Research Institute for Tropical Medicine
Address [1] 303290 0
9002 Research Dr, Alabang, Muntinlupa, 1781 Metro Manila, Philippines
Country [1] 303290 0
Philippines

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303811 0
Griffith University Human Research Ethics Committee
Ethics committee address [1] 303811 0
Ethics committee country [1] 303811 0
Australia
Date submitted for ethics approval [1] 303811 0
16/01/2012
Approval date [1] 303811 0
27/03/2012
Ethics approval number [1] 303811 0
PBH/24/11/HREC
Ethics committee name [2] 303813 0
Research Institute for Tropical Medicine Institutional Review Board
Ethics committee address [2] 303813 0
Ethics committee country [2] 303813 0
Philippines
Date submitted for ethics approval [2] 303813 0
06/02/2012
Approval date [2] 303813 0
07/05/2012
Ethics approval number [2] 303813 0
IRB#: 2012-13-0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 94894 0
Prof Allen Ross
Address 94894 0
Griffith University
Logan Campus
68 University Drive
Meadowbrook QLD 4131
Country 94894 0
Australia
Phone 94894 0
+61731625345
Fax 94894 0
Email 94894 0
[email protected]
Contact person for public queries
Name 94895 0
Allen Ross
Address 94895 0
Griffith University
Logan Campus
68 University Drive
Meadowbrook QLD 4131
Country 94895 0
Australia
Phone 94895 0
+61731625345
Fax 94895 0
Email 94895 0
[email protected]
Contact person for scientific queries
Name 94896 0
Allen Ross
Address 94896 0
Griffith University
Logan Campus
68 University Drive
Meadowbrook QLD 4131
Country 94896 0
Australia
Phone 94896 0
+61731625345
Fax 94896 0
Email 94896 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified data will be available upon request comprising individual participant data of published results. A code book of the variables will also be made available.
When will data be available (start and end dates)?
Data will me be made available on January 1, 2020 after the final trial results have been published. No end date is determined.
Available to whom?
The data will be made available to academic researchers, government organizations and non-government organizations upon request.
Available for what types of analyses?
No restriction will made on the type of analysis performed.
How or where can data be obtained?
Investigators seeking the trial data will be requested to contact the project leader, Professor Allen Ross, via e-mail (preferred) or telephone.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
3019Study protocol  [email protected]
3020Statistical analysis plan  [email protected]
3021Informed consent form  [email protected]
3022Clinical study report  [email protected]
3023Ethical approval  [email protected]
3024Analytic code  [email protected]



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.