03692nas a2200469   4500000000100000008004100001260002300042653005700065653001800122653004800140653006500188653002900253653002200282653002100304100001800325700001400343700001700357700001900374700001200393700001900405700001500424700001300439700001300452700002600465700002200491700001400513700001900527700001400546700001700560700001300577700001600590700001400606700001700620700001700637700001300654245026000667856010500927300000701032490000601039520216301045022001403208       2022                            d  bF1000 Research Ltd10aPublic Health, Environmental and Occupational Health10aHealth Policy10aImmunology and Microbiology (miscellaneous)10aBiochemistry, Genetics and Molecular Biology (miscellaneous)10aMedicine (miscellaneous)10aalbendazole (ALB)10aivermectin (IVM)1 aKrolewiecki A1 aEnbiale W1 aGandasegui J1 aVan Lieshout L1 aKepha S1 aMessa Junior A1 aBengtson M1 aGelaye W1 aEscola V1 aMartinez-Valladares M1 aCambra-Pellejà M1 aAlgorta J1 aMartí-Soler H1 aFleitas P1 aBallester MR1 aDoyle SR1 aWilliams NA1 aLegarda A1 aMandomando I1 aMwandawiro C1 aMuñoz J00aAn 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 of Trichuris trichiura and other STH infections. ALIVE trial protocol  uhttps://gatesopenresearch.org/articles/6-62/v1/pdf?article_uuid=cd652588-f5f9-4cc6-afdd-bba207a6a7fc  a620 v63 a<p>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).</p>
  a2572-4754