Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202202738940158 Date of Approval: 01/02/2022
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Impact of fatty meal co-administration and dual-dosing on albendazole effectiveness against hookworm among school-aged children in Mayuge district, Uganda
Official scientific title Impact of fatty meal co-administration and dual-dosing on albendazole effectiveness against hookworm among school-aged children in Mayuge district, Uganda
Brief summary describing the background and objectives of the trial In Uganda, a nationwide school-based prevalence survey was conducted in 2004 including 20,185 children from 207 schools, and the prevalence of STHs was 54.8%, which reduced to 8.8% in a 2016 nationwide school-based survey including 4,275 children from 120 schools. Hookworm was the dominant type of STHs both in the 2004 and 2016 study as the prevalence was 43.5% and 7.7%, respectively. However, despite the overall reduction between 2004 and 2016, the prevalence of hookworm increased in certain areas. World Vision, funded by Korea International Cooperation Agency (KOICA), has implemented comprehensive NTD elimination programs targeting STHs and schistosomiasis in Mayuge district, Uganda since 2019, known as the Mayuge NTDs Elimination (MANE) project. In 2019, a prevalence survey was done as the MANE baseline survey to understand the burden of STH and schistosomiasis in Mayuge district. Following the WHO guideline, the MANE team selected samples from 1,123 9-10 years old children who are equivalent to primary four (P4) and primary five (P5) grade students in the Ugandan education system. Mayuge district has implemented an annual MDA program against STH targeting school-aged children since 2003. According to the MANE baseline survey of 1,123 children in July 2019, the prevalence of hookworm was 15.1%, while the prevalence of Ascaris lumbricoides was 0% and the prevalence of Trichuris trichiura was 0.6%. Thus, in the Mayuge district, hookworm is the most common STH and will be the focus of the current study. Considering the cure rate (CR) for hookworm by single-dose albendazole is thought to be 78.4%, and the high program coverage of MDA for STHs (77.2%, 81.4%, and 75% in 2012, 2014, and 2016, respectively), the continued burden of hookworm in Mayuge district suggests that hookworm has developed mechanisms to overcome the MDA campaigns. Objectives The general objective is to investigate approaches for improving the effectiveness of albendazole treatment for curing hookworm infection. Specific objectives. Using data from a school-based prevalence survey, 1) To identify and evaluate environmental and social variables affecting hookworm infection. Using data from a nested trial, 2) To determine the effectiveness of albendazole administration with a fatty meal, such as avocado on hookworm cure rate and egg reduction rate. 3) To determine the effectiveness of dual-dose versus single-dose albendazole treatment regimens on hookworm cure rate and egg reduction rate.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Soil-transmitted helminth, hookworm infection
Purpose of the trial Treatment: Drugs
Anticipated trial start date 07/02/2022
Actual trial start date
Anticipated date of last follow up 06/03/2022
Actual Last follow-up date
Anticipated target sample size (number of participants) 210
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Simple randomization using a randomization table created by a computer software program Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group single dose albendazole with avocado 400mg of albendazole and 200grams of avocado One day The study aims to investigate the effectiveness of albendazole against hookworm infection with two interventions simultaneously; 1) dual-dose versus single-dose albendazole, 2) taking albendazole with or without fatty foods. Therefore, I decided to apply factorial randomised controlled trial for the study, since this design has the advantage of enabling investigation of the effects of two independent interventions concurrently and the effect of receiving both interventions together. When positive hookworm cases are identified through the prevalence survey in January and early February 2022, field workers will notify the students of "positive" results. These students will be asked to visit the most accessible health centre IV or hospital-level health facility in Mayuge district among four health facilities : 1) Mayuge health centre IV located in Mayuge town council, 2) Kigandalo health centre IV located in Kigandalo sub-county, 3) Kityerera health centre IV located in Kityerera sub-county, and 4) Buluuba hospital in Baitambogwe sub-county. The participants will be instructed to have a meal on the morning of the visit. These participants will be randomised into one group among four treatment options by applying the block randomisation method, stratified by health facility. The randomisation block size will be 8, and within each block there will be two participants allocated to each of the four trial arms. A randomisation list will be prepared beforehand using a random number generator. Each health facility will have its own random number list. One or two designated health worker(s) will be responsible for the trial in each health centre. I, as the central person, will communicate with a person in charge of each health centre to ensure randomisation proceeds as planned. The participants will be asked not to take a meal for at least four hours after the drug consumption to exclude the possibility of affecting albendazole absorption by immediately taking foods. But, water, and other non-caffeinated and non-alcoholic beverages can be allowed during the four hours fasting period. Albendazole (AGOZOLE produced by AGOG Pharmaceutical Ltd., India) from one batch will be used for the trial. AGOZOLE is an approved albendazole by the national drug authority (NDA) of Uganda and widely available drug in the Ugandan domestic pharmaceutical market. The trial is designed as an open-label randomised controlled trial with four arms: Intervention group 1: participants will take 400mg of single-dose albendazole with 200 grams of avocado. Intervention group 2: participants will take dual-dose albendazole (400mg of single-dose albendazole for two consecutive days) without taking avocado. Intervention group 3: participants will take dual-dose albendazole (400mg of single-dose albendazole for two consecutive days) with 200 grams of avocado on both occasions. Control group: Participants will take 400mg of single-dose albendazole without taking avocado. 52
Control Group Single dose albendazole without taking avocado Control group: Participants will take 400mg of single-dose albendazole without taking avocado. One day The Control group will receive only 400mg of single albendazole without avocado 54 Active-Treatment of Control Group
Experimental Group Dual dose albendazole without taking avocado 400mg of albendazole without taking 200 grams of avocado (two consecutive days) Two days The study aims to investigate the effectiveness of albendazole against hookworm infection with two interventions simultaneously; 1) dual-dose versus single-dose albendazole, 2) taking albendazole with or without fatty foods. Therefore, I decided to apply factorial randomised controlled trial for the study, since this design has the advantage of enabling investigation of the effects of two independent interventions concurrently and the effect of receiving both interventions together. When positive hookworm cases are identified through the prevalence survey in January and early February 2022, field workers will notify the students of "positive" results. These students will be asked to visit the most accessible health centre IV or hospital-level health facility in Mayuge district among four health facilities : 1) Mayuge health centre IV located in Mayuge town council, 2) Kigandalo health centre IV located in Kigandalo sub-county, 3) Kityerera health centre IV located in Kityerera sub-county, and 4) Buluuba hospital in Baitambogwe sub-county. The participants will be instructed to have a meal on the morning of the visit. These participants will be randomised into one group among four treatment options by applying the block randomisation method, stratified by health facility. The randomisation block size will be 8, and within each block there will be two participants allocated to each of the four trial arms. A randomisation list will be prepared beforehand using a random number generator. Each health facility will have its own random number list. One or two designated health worker(s) will be responsible for the trial in each health centre. I, as the central person, will communicate with a person in charge of each health centre to ensure randomisation proceeds as planned. The participants will be asked not to take a meal for at least four hours after the drug consumption to exclude the possibility of affecting albendazole absorption by immediately taking foods. But, water, and other non-caffeinated and non-alcoholic beverages can be allowed during the four hours fasting period. Albendazole (AGOZOLE produced by AGOG Pharmaceutical Ltd., India) from one batch will be used for the trial. AGOZOLE is an approved albendazole by the national drug authority (NDA) of Uganda and widely available drug in the Ugandan domestic pharmaceutical market. The trial is designed as an open-label randomised controlled trial with four arms: Intervention group 1: participants will take 400mg of single-dose albendazole with 200 grams of avocado. Intervention group 2: participants will take dual-dose albendazole (400mg of single-dose albendazole for two consecutive days) without taking avocado. Intervention group 3: participants will take dual-dose albendazole (400mg of single-dose albendazole for two consecutive days) with 200 grams of avocado on both occasions. Control group: Participants will take 400mg of single-dose albendazole without taking avocado. 52
Experimental Group Dual dose albendazole with taking avocado 400mg of albendazole with taking 200 grams of avocado (Two consecutive days) Two days The study aims to investigate the effectiveness of albendazole against hookworm infection with two interventions simultaneously; 1) dual-dose versus single-dose albendazole, 2) taking albendazole with or without fatty foods. Therefore, I decided to apply factorial randomised controlled trial for the study, since this design has the advantage of enabling investigation of the effects of two independent interventions concurrently and the effect of receiving both interventions together. When positive hookworm cases are identified through the prevalence survey in January and early February 2022, field workers will notify the students of "positive" results. These students will be asked to visit the most accessible health centre IV or hospital-level health facility in Mayuge district among four health facilities : 1) Mayuge health centre IV located in Mayuge town council, 2) Kigandalo health centre IV located in Kigandalo sub-county, 3) Kityerera health centre IV located in Kityerera sub-county, and 4) Buluuba hospital in Baitambogwe sub-county. The participants will be instructed to have a meal on the morning of the visit. These participants will be randomised into one group among four treatment options by applying the block randomisation method, stratified by health facility. The randomisation block size will be 8, and within each block there will be two participants allocated to each of the four trial arms. A randomisation list will be prepared beforehand using a random number generator. Each health facility will have its own random number list. One or two designated health worker(s) will be responsible for the trial in each health centre. I, as the central person, will communicate with a person in charge of each health centre to ensure randomisation proceeds as planned. The participants will be asked not to take a meal for at least four hours after the drug consumption to exclude the possibility of affecting albendazole absorption by immediately taking foods. But, water, and other non-caffeinated and non-alcoholic beverages can be allowed during the four hours fasting period. Albendazole (AGOZOLE produced by AGOG Pharmaceutical Ltd., India) from one batch will be used for the trial. AGOZOLE is an approved albendazole by the national drug authority (NDA) of Uganda and widely available drug in the Ugandan domestic pharmaceutical market. The trial is designed as an open-label randomised controlled trial with four arms: Intervention group 1: participants will take 400mg of single-dose albendazole with 200 grams of avocado. Intervention group 2: participants will take dual-dose albendazole (400mg of single-dose albendazole for two consecutive days) without taking avocado. Intervention group 3: participants will take dual-dose albendazole (400mg of single-dose albendazole for two consecutive days) with 200 grams of avocado on both occasions. 52
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1) Children identified with hookworm infection in the January 2022 prevalence survey 2) Children attending randomly selected P4 and P5 classes in one of the randomly selected schools 3) Children whose parents/guardians provide written informed consent for the prevalence survey and for the nested trial if hookworm infection is detected. 1) Children who received benzimidazole drugs such as albendazole and mebendazole within three months before the prevalence survey to avoid the residual effect of previously administrated drugs of albendazole. 2) Children who have a history of allergic reaction to albendazole or other benzimidazole drugs such as mebendazole. Child: 6 Year-12 Year 8 Year(s) 15 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 04/01/2022 London School of Hygiene and Tropical Medicine ethics committee
Ethics Committee Address
Street address City Postal code Country
Keppel street London WC1E 7HT United Kingdom
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 16/08/2021 Uganda national council for science and technology
Ethics Committee Address
Street address City Postal code Country
Plot 6, Kimera Road, Ntinda Kampala POBOX6884 Uganda
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 07/07/2021 Vector Control Division Research and Ethics Committee
Ethics Committee Address
Street address City Postal code Country
15 Bombo road Kampala POBOX1661 Uganda
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 24/01/2022 National Drug Authority
Ethics Committee Address
Street address City Postal code Country
Plot 19 Lumumba Avenue opposite TWED plaza Kampala POBX23096 Uganda
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Cure rate The cure rate (CR) is defined as the percentage of infected individuals at prevalence survey that are free of infection three weeks after treatment. three weeks after the trial
Primary Outcome Egg reduction rate (ERR) Egg per gram (EPG): With the Kato-Katz method, the measure of EPG is obtained by multiplying the number of eggs counted on the slide. Considering the slide template holds 41.7mg of faeces, the multiplication factor to obtain EPG is 24. Three weeks after the trial
Secondary Outcome Adverse events from the clinical trial within two days of the clincal trial day
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Mayuge office of World Vision Uganda World Vision Mayuge Office, Mayuge T/C, Mayuge Uganda
FUNDING SOURCES
Name of source Street address City Postal code Country
KOICA 825 Daewangpangyo-ro, Sujeong-gu, Seongnam 13449 Korea, Republic of
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor World Vision Uganda Plot 15B, Nakasero road Kampala POBOX5319 Uganda Charities/Societies/Foundation
COLLABORATORS
Name Street address City Postal code Country
Vector Control Division Queens Ln Kampala POBOX1661 Uganda
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Eun Seok Kim eunseok_kim@wvi.org +256757143771 Plot 15B, Nakasero Rd
City Postal code Country Position/Affiliation
Kampala POBOX5319 Uganda Health specialist
Role Name Email Phone Street address
Scientific Enquiries Emily Webb Emily.Webb@lshtm.ac.uk +4402079272012 Keppel street
City Postal code Country Position/Affiliation
London WC1E 7HT United Kingdom Professor
Role Name Email Phone Street address
Public Enquiries Bomax Otim Bomx_Otim@wvi.org +256755002670 Plot 15B, Nakasero Rd
City Postal code Country Position/Affiliation
Kampala POBOX Uganda Project coordinator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual Participant Data (IPD) consist of raw participant data and/or cleaned, anonymized, and analyzable datasets. The information on the participants to the study will not be saved by the participant’s name but by identification number. All participants’ information containing hard copies will be kept in locked cabinets of the sponsor (World Vision Uganda) and will not be shared with anyone except the research team and the designated person in charge of Vector-borne control and NTD control department of the Ministry of Health Uganda. Informed Consent Form,Statistical Analysis Plan,Study Protocol within two years after completing the trial - All participants’ information containing hardcopies will be kept in locked cabinets of the sponsor (World Vision Uganda) and will not be shared with anyone except the research team and the designated person in charge of Vector-borne control and NTD control department of the ministry of health Uganda. - Collected data through ODK synchronised devices will be saved in the devices and the data in the tablet PCs and smartphones will be transferred to the World Vision’s ODK server. Only authorised World Vision staff can access the World Vision’s server.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information