An adaptive phase II/III safety and efficacy randomized controlled trial of single day or three-day fixed-dose albendazole-ivermectin co-formulation versus albendazole for the treatment ofTrichuris trichiuraand other STH infections. ALIVE trial protocol

Gates Open Research

article

Alejandro Krolewiecki¹  Wendemagegn Enbiale³  Javier Gandasegui¹  Lisette van Lieshout⁵  Stella Kepha⁶  Augusto Messa Junior⁷  Michel Bengtson⁵  Woyneshet Gelaye³  Valdemiro Escola⁷  María Martinez-Valladares⁸  María Cambra-Pellejà⁸  Jaime Algorta^1,10  Helena Martí-Soler¹  Pedro Fleitas¹  Maria Rosa Ballester^1,11  Stephen R. Doyle^1,14  Nana Aba Williams¹  Almudena Legarda¹  Inácio Mandomando⁷  Charles Mwandawiro⁶  José Muñoz¹ 

[1] Barcelona Institute for Global Health ,(ISGlobal), Hospital Clínic—Universitat de Barcelona;Instituto de Investigaciones de Enfermedades Tropicales, Universidad Nacional de Salta;College of Medicine and Health Science, Bahir Dar University;Department of Dermatology,, Amsterdam Institute for Infection and Immunity, Academic Medical Centre;Department of Parasitology, Centre of Infectious Diseases, Leiden University Medical Centre;Eastern and Southern Africa Centre of International Parasite Control, Kenya Medical Research Institute;Centro de Investigação em Saúde de Manhiça;Instituto de Ganadería de Montaña, CSIC-Universidad de León;Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad de León, Campus de Vegazana;Liconsa SA;Institut d’Investigació Biomèdica Sant Pau;Faculty of Health Sciences Blanquerna,, University Ramon Llull;Centro de Investigación Biomédica en Red de Salud Mental;Wellcome Sanger Institute

关键词: Antihelmintics;    STH;    Trichuris trichiura;    Strongyloides;    Hookworm;    Albendazole;    Ivermectin;   

DOI  :  10.12688/gatesopenres.13615.1

学科分类：电子与电气工程

来源: American Journal Of Pharmtech Research

【 摘 要 】

Background: Soil-transmitted helminths (STH) are targeted for control through mass drug-administration campaigns to prevent morbidity affecting at-risk groups in endemic regions. Although broadly successful, the use of albendazole and mebendazole achieved variable progress, with deficiencies against Trichuris trichiura and a predictable low efficacy against Strongyloides stercoralis. Novel drug combinations offer a potential solution, providing they can be delivered safely and maintain efficacy against all STH species. Here we present the protocol of a clinical trial to evaluate a fixed-dose combination (FDC) tablet containing albendazole and ivermectin that will be compared against albendazole against STH. Methods: An adaptive phase II/III randomized controlled trial will be undertaken in STH endemic sites in Ethiopia, Kenya and Mozambique to evaluate an oral FDC of 400 mg albendazole and either 9- or 18 mg ivermectin. FDC will be administered as a single dose or single doses over three-consecutive days and assessed against a single dose of 400 mg albendazole. In the phase II trial, 126 T. trichiura-infected children weighting 15 to 45 kg will be treated in a dose-escalation manner to determine safety objectives. In the phase III trial, 1097 participants aged 5 to 18 years old infected with T. trichiura, hookworm and S. stercoralis will be recruited to determine safety and efficacy. The trial will be open-label with blinded outcome assessors. Cure rate measured 21-days after-treatment in duplicate Kato-Katz is the primary efficacy outcome. Secondary objectives include efficacy evaluation by quantitative polymerase chain reaction (PCR) as an outcome measurement, description of pharmacokinetic parameters, palatability and acceptability evaluations, and monitoring of anthelmintic resistance. Conclusions: This trial with registrational goals seeks to evaluate an innovative fixed-dose combination of albendazole and ivermectin co-formulated tablets, with the goal of providing an anthelmintic regimen with improved efficacy and spectrum of coverage against STH. ClinicalTrials.gov registration: NCT05124691 (18/11/2021).

【 授权许可】

CC BY