Tribendimidine for the treatment of liver fluke infection in Southeast Asia in Laos

ISRCTN	ISRCTN96948551
DOI	https://doi.org/10.1186/ISRCTN96948551
Secondary identifying numbers	N/A

Submission date: 07/09/2012
Registration date: 18/09/2012
Last edited: 23/01/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Opisthorchiasis and clonorchiasis are parasitic liver fluke infections that are of considerable public health significance in Southeast Asia. There is currently no vaccine available for prevention of liver fluke infections, and hence drug treatment is the current mainstay for clearing infections and subsequently reducing illness. However, treatment of opisthorchiasis relies on a single drug, praziquantel. Efforts are underway to more widely administer praziquantel to prevent infections. There is some concern that this strategy might result in the development and spread of drug-resistant parasites. Against this background, there is a need for new drugs. The aim of this study is to assess the effectiveness and safety of oral tribendimidine, a Chinese anti-parasitic drug, in patients with opisthorchiasis.

Who can participate?
Patients aged over 8 with opisthorchiasis.

What does the study involve?
In the first part of the study, participants are assigned to six different groups depending on age. Children aged 8-14 are randomly allocated into three groups, with each group receiving a different dose of tribendimidine. Adults and adolescents aged 15 and above are also randomly allocated into three groups, with each group receiving a different dose of tribendimidine. Blood and stool samples are taken. In the second part of the study, participants are randomly allocated into one of two groups. One group receives the most effective dose of tribendimidine as identified in the first part of the study. The other group is treated with praziquantel in two divided doses. This part of the study is only carried out if the results of the first part of the study are satisfactory. All patients are closely monitored for illness during the period of drug administration. Patients who report adverse events are examined carefully by the study doctor and, when necessary, medical action is taken on the spot or patients are referred to a nearby hospital.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
Swiss Tropical and Public Health Institute (Switzerland)

When is the study starting and how long is it expected to run for?
October 2012 to September 2013

Who is funding the study?
Department for International Development (UK), Medical Research Council (UK), Wellcome Trust (UK)

Who is the main contact?
Dr Peter Odermatt

Contact information

Dr Peter Odermatt
Scientific

Swiss Tropical and Public Health Institute
Socinstrasse 57
Postfach
4002
4002
Switzerland

Study information

Study design	Randomized controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Other
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	Tribendimidine for the treatment of liver fluke infection in Southeast Asia in Laos
Study acronym	TribOvL
Study objectives	Current study hypothesis as of 06/02/2017: 1. Tribendimidine dosage for the treatment of Opisthorchis viverrini liver fluke is the same as the dosage for the other intestinal parasitic infections 2. Tribendimidine is non inferior than the current standard treatment with praziquantel (non-inferiority margin set at 3%-pts for difference in cure rates) Previous study hypothesis: 1. Tribendimidine dosage for the treatment of Opisthorchis viverrini liver fluke is the same as the dosage for the other intestinal parasitic infections 2. Tribendimidine has a higher efficacy and fewer adverse events than the current standard treatment with praziquantel
Ethics approval(s)	1. Ethics Committee of the Canton of Basel and Baselland, 09/02/2012, ref: EKBB 375/11 2. National Ethics Committee Laos, Ministry of Health 3. Liverpool School of Tropical Medicine, Research Ethics Committee, 03/05/2012, ref: 12.02RS
Health condition(s) or problem(s) studied	Liver fluke (Opisthorchis viverrini) infection
Intervention	1. Dose finding 2a trial: Children aged 0 to 14 years will be randomized into 3 groups: Group 1 will receive 50 mg Group 2 will receive 100 mg Group 3 200mg tribendimidine. Patients aged 15 years and above will also be randomized into three treatment roups: group 1 will be receive a treatment dose of 100 mg, group 2 200 mg and group 3 400 mg of tribendimidine. Study participants will be randomly assigned to one of these arms using a computerized block randomization procedure. 2. Randomised controlled trial 2b: Most efficacious tribendimidine dosage of trial compared with praziquantel 75mg/kg BW devided in two doses (50 mg/kg BW, 25 mg /kg BW) 4 hours apart
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Tribendimidine, praziquantel
Primary outcome measure	O. viverrini infection: cure rates and egg reduction rates
Secondary outcome measures	1. Adverse events observed with tribendimidine and praziquantel 2. PK parameters of tribendimidine in patients infected with O. viverrini 3. Co-infection with soil-transmitted helminths (hookworm, A. lumbricoides, T. trichiura)
Overall study start date	01/10/2012
Completion date	30/09/2013

Eligibility

Participant type(s)	Patient
Age group	Mixed
Sex	Both
Target number of participants	900
Key inclusion criteria	1. Patients (older than 8 years) infected with O. viverrini (respectively: C. sinensis in PR China), as assessed by the presence of eggs in the stool 2. Able and willing to be examined by a study physician at the beginning of the study and at the end-of study (3 weeks post-treatment) 3. Able and willing to provide 2 stool samples at the beginning and end of study 4. Absence of major systemic illnesses, as assessed by the medical doctor, upon initial clinical assessment 5. Absence of psychiatric and neurological disorders 6. No known or reported hypersensitivity to tribendimidine 7. No known or reported history of chronic illness as cancer, diabetes, chronic heart, liver or renal disease 8. Signed written informed consent sheet 9. For females aged 12 years and above, not pregnant, as assessed by a female nurse (interview and pregnancy test), upon initial clinical assessment
Key exclusion criteria	1. Pregnancy 2. Presence of any abnormal medical condition, judged by the study physician. 3. Concurrent non-helminthic infectious disease as judged by the study clinician (for malaria, use rapid diagnostic test to diagnose). 4. History of acute or severe chronic disease 5. Known or reported psychiatric or neurological disorders 6. Use of praziquantel and other helminth treatment within the past three months 7. Attending other clinical trials during the study
Date of first enrolment	01/10/2012
Date of final enrolment	30/09/2013

Locations

Countries of recruitment

Lao People's Democratic Republic
Switzerland

Study participating centre

Swiss Tropical and Public Health Institute

4002
4002
Switzerland

Sponsor information

Swiss Tropical and Public Health Institute (Switzerland)
Research organisation

c/o Dr eter Odermatt
Socinstrasse 57
Postfach
Basel
4002
Switzerland

Website	http://www.swisstph.ch/
"ROR"	https://ror.org/03adhka07

Funders

Funder type

Government

Department for International Development
Government organisation / National government

Alternative name(s): Department for International Development, UK, DFID
Location: United Kingdom

Medical Research Council (ref: G1100699)
Government organisation / National government

Alternative name(s): Medical Research Council (United Kingdom), UK Medical Research Council, MRC
Location: United Kingdom

Wellcome Trust (ref: 096471)
Private sector organisation / International organizations

Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/10/2016		Yes	No
Results article	results	01/02/2018		Yes	No

Editorial Notes

23/01/2019: Publication reference added.
01/08/2016: Publication reference added.