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 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202011642671155 Date of Registration: 03/11/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Evaluation of the effectiveness of ALBENDAZOL‐IVERMECTIN co‐formulation vs ALBENDAZOLE for the treatment of intestinal worms.
Official scientific title An Adaptive phase II/III Single‐Blinded, Randomized, Multi‐Centre, Parallel‐Group, Active‐Controlled, Superiority Study to Evaluate the Safety and Efficacy of a Single Day or 3‐day Single Dose of an ALBENDAZOLE‐IVERMECTIN Coformulation vs ALBENDAZOLE for the Treatment of Soil‐Transmitted Helminth Infections (Trichuris trichiura, hookworm, Strongyloides stercoralis) in Paediatric and Young Adult Population.
Brief summary describing the background and objectives of the trial he purpose of this clinical trial is to evaluate a fixed-dose co-formulation (FDC) of ivermectin and albendazole for the treatment of all Soil Transmitted helminths (STH). The current strategy to control STH in endemic areas is mass administration of albendazole or mebendazole, mainly to pre-school and school-aged children. Although this treatment works well for some STH species, efficacy against Trichuris trichiura is poor and it is not effective Strongyloides stercoralis. Thus new drugs or drug combinations are an urgent priority to increase the effectiveness of control programmes. Furthermore, the World Health Organisation has recommended combination therapy of ivermectin with albendazole. The trial proposed, is an adaptive phase II/III trial where the phase II component will evaluate the safety of the FDC as a single dose or 3-day single dose regimen for the treatment of T. trichiura in paediatric population. After analysis of the safety results the phase III trial will be executed to evaluate the efficacy of the FDC as a single dose or 3-day single dose regimen compared to the standard single dose regimen of ALB (400 mg) for the treatment of T. trichiura, hookworm and S. stercoralis in paediatric and young adult population. The estimated total sample size for the adaptive design (phase II and III component) is 1223 participants. Of these, 126 will be enrolled in the phase II and 1097 in the phase III components respectively in an adaptive trial design.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) ALIVE
Disease(s) or condition(s) being studied Infections and Infestations,Paediatrics
Sub-Disease(s) or condition(s) being studied Soil-transmitted helminths
Purpose of the trial Treatment: Drugs
Anticipated trial start date 02/08/2021
Actual trial start date 19/01/2022
Anticipated date of last follow up 31/07/2023
Actual Last follow-up date
Anticipated target sample size (number of participants) 1223
Actual target sample size (number of participants)
Recruitment status 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
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomization Sealed opaque envelopes Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Albendazole 400 mg Single dose Current standard of care treatment for STH infection: Albendazole 400 mg single dose 251 Active-Treatment of Control Group
Experimental Group FDCx1. Albendazole and Ivermectin Fixed Dose Coformulation 400 mg Albendazole - 9 mg Ivermectin OR 400 mg Albendazole - 18 mg Ivermectin Single dose Single dose of a tablet of FDC 400mg‐18mg or 400mg‐9mg. (i) For participants <45 kg of body weight at baseline: FDC of 400mg ALB‐ 9mg IVM. (ii) For participants ≥45 kg of body weight at baseline: FDC of 400mg ALB‐18mg IVM. 419
Experimental Group FDCx3. Albendazole and Ivermectin Fixed Dose Coformulation 3 days 400 mg Albendazole - 9 mg Ivermectin OR 400 mg Albendazole - 18 mg Ivermectin for 3 days 3-day single-dose Daily dose of a tablet of FDC 400mg‐18mg or 400mg‐ 9mg for 3 days. (i)For participants <45 kg of body weight at baseline: FDC of 400mg ALB‐9mg IVM. (ii) For participants ≥45 kg of body weight at baseline: FDC of 400mg ALB‐ 18mg IVM. 427
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Positive infection test by microscopy for at least one of the following STH: T. trichiura, hookworms and/or larvae of S. stercoralis. Weight ≥15 Kg. Male or female, aged 5 to 18 years. Female participants who are ≥12 years old (or female post‐menarche) must have a negative urine pregnancy test at screening or at the time of randomization. Ability to take oral medication and willingness to comply with all study procedures. Parental acceptance to participate in the study by obtaining a signed and dated informed consent form approved by the Regulatory authorities. In addition, verbal assent will be obtained from children aged 12–18 years. Intake of ALB, mebendazole and/or IVM, or any potentially interacting drug three months before screening. Residence outside the study area or planning to move away in the four weeks following recruitment. Epidemiological risk of infection by Loa loa. Serious medical illness, per investigator’s criteria. Any participant’s condition that would prevent the appropriate evaluation and follow‐up, as per investigator’s criteria. Known hypersensitivity to any components of either of the study treatment. Positive pregnancy urine test, pregnant or first week post‐partum. Adolescent: 13 Year(s)-17 Year(s),Child: 6 Year-12 Year,Preschool Child: 2 Year-5 Year 5 Year(s) 18 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 14/07/2020 Kenya Medical Research Institute KEMRI Scientific and Ethical Review Committee
Ethics Committee Address
Street address City Postal code Country
Secretary SERU, KEMRI, P. O. BOX 54840-00200, Nairobi Nairobi 54840-002 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Cure rate (CR) for T. trichiura 21 days after treatment, as determined by microscopy (efficacy T. trichiura). 21 days
Secondary Outcome CR for hookworm and S. stercoralis 21 days after treatment, as determined by microscopy (efficacy hookworm and S. stercoralis). 21 days
Secondary Outcome Egg reduction rate (ERR) for T. trichiura 21 days after treatment, by microscopy. 21 days
Secondary Outcome Frequency, type, severity and relationship to study drug for all adverse events and severe adverse events for ALB, FDC and FDCx3 (safety). 21 days
Secondary Outcome CR for T. trichiura, hookworm and S. stercoralis, by PCR. 21 days
Secondary Outcome Parasite burden decrease after 21 days for hookworm, T. trichiura and S. stercoralis, by PCR. 21 days
Secondary Outcome Evaluation of genotypic albendazole resistance in the three arms. 21 days
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Kenya Medical Research Institute ESACIPAC Kenya Medical research Institute KEMRI ESACIPAC Nairobi 54840-002 Kenya
Fundacao Manhica Bairro Cambeve, Rua 12, Distrito da Manhica Manhica 1929 Mozambique
Bahir Dar University Colleges of Medicine and Health Sciences Bahir Dar PO BOX 79 Ethiopia
FUNDING SOURCES
Name of source Street address City Postal code Country
EDCTP European and Developing Countries Clinical Trial Partnership Anna van Saksenlaan 51 The Hague 2593 HW Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Barcelona Institute for Global Health ISGlobal Carrer del Rossello 132 7th floor Barcelona 08036 Spain Research Organisation
COLLABORATORS
Name Street address City Postal code Country
Academisch Ziekenhuis Leiden LUMC Albinusdreef 2 Leiden 2333 ZA Netherlands
Bahir Dar University Colleges of Medicine and Health Sciences Bahir Dar PO BOX 79 Ethiopia
Fundacao Manhica Bairro Cambeve, Rua 12, Distrito da Manhica Manhica 1929 Mozambique
London School of Hygiene and Tropical Medicine Keppel St, Bloomsbury London WC1E 7HT United Kingdom
Kenya Medical Research Institute Kilimani Mbagathi Rd HOUSE NUMBER 8 Nairobi 54840 Kenya
Laboratorios Liconsa Av. de Miralcampo, 7 Azuqueca de Henares 19200 Spain
Universidad de Leon Instituto de Ganaderia de Montana CSIC Universidad de Leon Grulleros 24346 Spain
Barcelona Institute for Global Health ISGlobal Carrer del Rossello 132 7th floor Barcelona 08036 Spain
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Jose Munoz Gutierrez jose.munoz@isglobal.org +34932273288 Carrer del Rossello 132 4th floor
City Postal code Country Position/Affiliation
Barcelona 08036 Spain Associate Research Professor
Role Name Email Phone Street address
Public Enquiries Marc Fernandez Pardos marc.fernandez@isglobal.org +34932274112 Rossello Street 4th floor
City Postal code Country Position/Affiliation
Barcelona 08036 Spain Project Manager
Role Name Email Phone Street address
Scientific Enquiries Alejandro Krolewiecki alekrol@hotmail.com +543878421924 Instituto de Investigaciones de Enfermedades Tropicales Universidad Nacional de Salta. Alvarado 751
City Postal code Country Position/Affiliation
Oran 4530 Argentina CONICET Independant Researcher. Instituto de Investigaciones de Enfermedades Tropicales Universidad Nacional de Salta
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Data generated in each trial site will be stored on-site and data from all three sites will be centralized at ISGlobal, the Sponsor institution. This will not include the participant's contact or identifying information. All necessary steps to protect the confidentiality required in human participant research will be taken. Data for analysis will be free of identifiers that would permit linkage to the trial participants. Study Protocol The trial is expected to start in August 2021 and finish in November 2022. Individual Participant Data will be available after the trial is completed. All data generated will be centralised at ISGlobal (Sponsor and coordinating centre). Sharing of data to third parties will be decided upon by the consortium. Any data shared will be done in a controlled manner
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://stoptheworm.org/ 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