{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:09:58Z","timestamp":1772168998158,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/gatesopenres.13299.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T00:00:00Z","timestamp":1632700800000}}],"reference-count":34,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T00:00:00Z","timestamp":1632700800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1153928"],"award-info":[{"award-number":["OPP1153928"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["gatesopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Gates Open Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Background:<\/ns4:bold>\n                    Infections with soil-transmitted helminths (STHs) predominantly affect impoverished populations in tropical environments. The periodic administration of single dose benzimidazoles (i.e., albendazole, mebendazole) to at-risk individuals in endemic regions is at the center of STH control strategies. Given the low efficacy of these drugs against trichuriasis, investigation of drug combinations including moxidectin and ivermectin has recently been initiated, yet the identification of the best treatment option requires more research. We present the protocol for a trial investigating the efficacy and safety of co-administered moxidectin and albendazole compared to co-administered ivermectin and albendazole against\n                    <ns4:italic>Trichuris trichiura<\/ns4:italic>\n                    .\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods:<\/ns4:bold>\n                    We will conduct a randomized controlled trial enrolling 540\n                    <ns4:italic>T. trichiura<\/ns4:italic>\n                    -infected adolescents aged 12-19 years on Pemba Island (Tanzania). The trial will be open-label with blinded outcome assessors. The primary objective is to demonstrate non-inferiority of orally co-administered single-dose moxidectin (8 mg)\/albendazole (400 mg) compared to orally co-administered single-dose ivermectin (200 \u00b5g\/kg)\/albendazole (400 mg) in terms of egg reduction rates (ERRs) against\n                    <ns4:italic>T. trichiura<\/ns4:italic>\n                    infections assessed by Kato-Katz at 14-21 days post-treatment. Secondary objectives include the assessment of the drug combinations\u2019 superiority compared to their respective monotherapies, of the cure rates (CRs) against\n                    <ns4:italic>T. trichiura<\/ns4:italic>\n                    , and the safety and tolerability of all treatments, as well as CRs and ERRs against concomitant STH infections (\n                    <ns4:italic>Ascaris lumbricoides<\/ns4:italic>\n                    and hookworm). Potential effects of the treatment regimens on follow-up prevalences of STH at 5-6 weeks and 3 months post-treatment and pharmacokinetic\/\u00a0 pharmacodynamic parameters will also be assessed.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusions:<\/ns4:bold>\n                    Results from this trial will help to inform decision- and policymakers on which anthelminthic combination therapy might improve existing deworming programs and provide a valuable adjunct tool for interrupting STH transmission.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Clinicaltrials.gov<\/ns4:bold>\n                    <ns4:bold>registration:<\/ns4:bold>\n                    NCT04700423 (07\/01\/2021)\n                  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M.","family":"Ali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0290-3521","authenticated-orcid":false,"given":"Jennifer","family":"Keiser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2021,9,27]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"j4307","DOI":"10.1136\/bmj.j4307","article-title":"Efficacy of recommended drugs against soil transmitted helminths: systematic review and network meta-analysis.","volume":"358","author":"W Moser","year":"2017","journal-title":"BMJ."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"S253-S259","DOI":"10.1093\/cid\/ciy002","article-title":"Investigating the effectiveness of current and modified World Health Organization guidelines for the control of soil-transmitted helminth infections.","volume":"66","author":"S Farrell","year":"2018","journal-title":"Clin Infect Dis."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"459-71","DOI":"10.1038\/nrg3922","article-title":"Evolutionary consequences of drug resistance: shared principles across diverse targets and organisms.","volume":"16","author":"D Hughes","year":"2015","journal-title":"Nat Rev Genet."},{"key":"ref-4","article-title":"The selection and use of essential medicines: report of the 21st WHO Expert Committee","year":"2017"},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"91-115","DOI":"10.1016\/bs.apar.2018.08.002","article-title":"Drug combinations against soil-transmitted helminth infections.","volume":"103","author":"W Moser","year":"2019","journal-title":"Adv Parasitol."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"e0006458","DOI":"10.1371\/journal.pntd.0006458","article-title":"Efficacy and safety of co-administered ivermectin plus albendazole for treating soil-transmitted helminths: a systematic review, meta-analysis and individual patient data analysis.","volume":"12","author":"M Palmeirim","year":"2018","journal-title":"PLoS Negl Trop Dis."},{"key":"ref-7","doi-asserted-by":"publisher","DOI":"10.2139\/ssrn.3814770","article-title":"Efficacy and Safety of Co-Administered Ivermectin and Albendazole in School-Aged Children and Adults Infected With Trichuris trichiura: A Multi-Country Randomized Controlled Trial","author":"E H\u00fcrlimann","year":"2021"},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"864-873","DOI":"10.1016\/S1473-3099(18)30233-0","article-title":"Efficacy and tolerability of moxidectin alone and in co-administration with albendazole and tribendimidine versus albendazole plus oxantel pamoate against Trichuris trichiura infections: a randomised, non-inferiority, single-blind trial.","volume":"18","author":"B Barda","year":"2018","journal-title":"Lancet Infect Dis."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"1193-1201","DOI":"10.1093\/cid\/ciz326","article-title":"Efficacy and Safety of Ascending Dosages of Moxidectin and Moxidectin-albendazole Against Trichuris trichiura in Adolescents: A Randomized Controlled Trial.","volume":"70","author":"L Keller","year":"2020","journal-title":"Clin Infect Dis."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"5200-4","DOI":"10.1128\/AAC.00311-11","article-title":"Excretion of moxidectin into breast milk and pharmacokinetics in healthy lactating women.","volume":"55","author":"J Korth-Bradley","year":"2011","journal-title":"Antimicrob Agents Chemother."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"1207-1216","DOI":"10.1016\/S0140-6736(17)32844-1","article-title":"Single dose moxidectin versus ivermectin for Onchocerca volvulus infection in Ghana, Liberia, and the Democratic Republic of the Congo: a randomised, controlled, double-blind phase 3 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Geary","year":"2010","journal-title":"Int J Parasitol."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"1025-35","DOI":"10.1007\/s00228-010-0851-0","article-title":"A systematic review of pharmacokinetics studies in children with protein-energy malnutrition.","volume":"66","author":"K Oshikoya","year":"2010","journal-title":"Eur J Clin Pharmacol."},{"key":"ref-16","doi-asserted-by":"publisher","first-page":"1108-15","DOI":"10.1177\/0091270003257456","article-title":"The antiparasitic moxidectin: safety, tolerability, and pharmacokinetics in humans.","volume":"43","author":"M Cotreau","year":"2003","journal-title":"J Clin Pharmacol."},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"122-125","DOI":"10.4269\/ajtmh.2012.11-0415","article-title":"The effect of a high-fat breakfast on the pharmacokinetics of moxidectin in healthy male subjects: a randomized phase I trial.","volume":"86","author":"J Korth-Bradley","year":"2012","journal-title":"Am J Trop Med Hyg."},{"key":"ref-18","doi-asserted-by":"publisher","first-page":"720-7","DOI":"10.1016\/s0020-7519(01)00174-6","article-title":"Selection of different genotype larvae and adult worms for anthelmintic resistance by persistent and short-acting avermectin\/milbemycins.","volume":"31","author":"E Barnes","year":"2001","journal-title":"Int J Parasitol."},{"key":"ref-19","article-title":"Efficacy and Safety of MOX\/ALB vs. IVM\/ALB co-administration","author":"S Welsche","year":"2021"},{"key":"ref-20","article-title":"U.S. FDA approves moxidectin for the treatment of river blindness.","year":"2018"},{"key":"ref-21","first-page":"397-400","article-title":"A simple device for quantitative stool thick-smear technique in Schistosomiasis mansoni.","volume":"14","author":"N Katz","year":"1972","journal-title":"Rev Inst Med Trop Sao Paulo."},{"key":"ref-22","article-title":"Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity","year":"2011"},{"key":"ref-23","doi-asserted-by":"publisher","first-page":"e02489-18","DOI":"10.1128\/AAC.02489-18","article-title":"Pharmacokinetics of Albendazole, Albendazole Sulfoxide, and Albendazole Sulfone Determined from Plasma, Blood, Dried-Blood Spots, and Mitra Samples of Hookworm-Infected Adolescents.","volume":"63","author":"J Schulz","year":"2019","journal-title":"Antimicrob Agents Chemother."},{"key":"ref-24","doi-asserted-by":"publisher","first-page":"122556","DOI":"10.1016\/j.jchromb.2021.122556","article-title":"Development and validation of an LC-MS\/MS method for the quantification of the anthelmintic drug moxidectin in a volumetric absorptive microsample, blood, and plasma: Application to a pharmacokinetic study of adults infected with Strongyloides stercoralis in Laos.","volume":"1166","author":"D Hofmann","year":"2021","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci."},{"key":"ref-25","doi-asserted-by":"publisher","first-page":"2901-2909","DOI":"10.1039\/C8AY00828K","article-title":"Development and validation of a LC-MS\/MS method for ivermectin quantification in dried blood spots: application to a pharmacokinetic study in Trichuris trichiura-infected adults.","volume":"10","author":"J Schulz","year":"2018","journal-title":"Anal Methods."},{"key":"ref-26","doi-asserted-by":"publisher","first-page":"1420-8","DOI":"10.1086\/657310","article-title":"Albendazole and mebendazole administered alone or in combination with ivermectin against Trichuris trichiura: a randomized controlled trial.","volume":"51","author":"S Knopp","year":"2010","journal-title":"Clin Infect Dis."},{"key":"ref-27","doi-asserted-by":"publisher","first-page":"856-63","DOI":"10.4269\/ajtmh.2008.79.856","article-title":"Efficacy of ivermectin and albendazole alone and in combination for treatment of soil-transmitted helminths in pregnancy and adverse events: a randomized open label controlled intervention trial in Masindi district, western Uganda.","volume":"79","author":"R Ndyomugyenyi","year":"2008","journal-title":"Am J Trop Med Hyg."},{"key":"ref-28","doi-asserted-by":"publisher","first-page":"277-284","DOI":"10.1016\/S1473-3099(14)71050-3","article-title":"Efficacy and safety of albendazole plus ivermectin, albendazole plus mebendazole, albendazole plus oxantel pamoate, and mebendazole alone against Trichuris trichiura and concomitant soil-transmitted helminth infections: a four-arm, randomised controlled trial.","volume":"15","author":"B Speich","year":"2015","journal-title":"Lancet Infect Dis."},{"key":"ref-29","article-title":"ICH Topic E2A, Clinical Safety Data Management: Definitions and Standards for Expedited Reporting","year":"1995"},{"key":"ref-30","doi-asserted-by":"publisher","first-page":"91-115","DOI":"10.1016\/bs.apar.2018.08.002","article-title":"Drug Combinations Against Soil-Transmitted Helminth Infections.","volume":"103","author":"W Moser","year":"2019","journal-title":"Adv Parasitol."},{"key":"ref-31","first-page":"35-42","article-title":"A comparison of the efficacy of single doses of albendazole, ivermectin, and diethylcarbamazine alone or in combinations against Ascaris and Trichuris spp.","volume":"81","author":"V Belizario","year":"2003","journal-title":"Bull World Health Organ."},{"key":"ref-32","doi-asserted-by":"publisher","first-page":"477-81","DOI":"10.4269\/ajtmh.1996.55.477","article-title":"A comparative trial of a single-dose ivermectin versus three days of albendazole for treatment of Strongyloides stercoralis and other soil-transmitted helminth infections in children.","volume":"55","author":"H Marti","year":"1996","journal-title":"Am J Trop Med Hyg."},{"key":"ref-33","doi-asserted-by":"publisher","first-page":"1151-1160","DOI":"10.1016\/S1473-3099(20)30691-5","article-title":"Efficacy and safety of ascending doses of moxidectin against Strongyloides stercoralis infections in adults: a randomised, parallel-group, single-blinded, placebo-controlled, dose-ranging, phase 2a trial.","volume":"21","author":"D Hofmann","year":"2021","journal-title":"Lancet Infect Dis."},{"key":"ref-34","doi-asserted-by":"publisher","first-page":"1067-1081","DOI":"10.1080\/14787210.2020.1792772","article-title":"Moxidectin: an oral treatment for human onchocerciasis.","volume":"18","author":"P Milton","year":"2020","journal-title":"Expert Rev Anti Infect Ther."}],"container-title":["Gates Open 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/gatesopenres.14639.r31216, Judd L. Walson, Department of Global Health, University of Washington, Seattle, WA, USA, 01 Oct 2021, version 2, indexed","URL":"https:\/\/gatesopenresearch.org\/articles\/5-106\/v2#referee-response-31216","order":0,"name":"referee-response-31216","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/gatesopenres.14639.r31217, Alejandro Krolewiecki, Pedro Fleitas, Instituto de Investigaciones de Enfermedades Tropicales (IIET-CONICET), Sede Regional Or\u00e1n, Universidad Nacional de Salta, Or\u00e1n, Argentina, 01 Oct 2021, version 2, indexed","URL":"https:\/\/gatesopenresearch.org\/articles\/5-106\/v2#referee-response-31217","order":1,"name":"referee-response-31217","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by the Bill and Melinda Gates Foundation [OPP1153928]. The Swiss TPH acts as sponsor of the study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}