{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:37:26Z","timestamp":1791596246751,"version":"4.3.4"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T00:00:00Z","timestamp":1659571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014054","name":"Drugs for Neglected Diseases Initiative","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014054","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Chagas Control Program in Bolivia"},{"name":"Spanish Agency for Cooperation"},{"DOI":"10.13039\/501100008530","name":"FEDER","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Institutes of Health\/National Institute on Minority Health and Health Disparaties"},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chagas disease (CD) has significant global health impact, but safe, effective treatments remain elusive. The nitroimidazole fexinidazole is a potential treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This double-blind, randomized, placebo-controlled, dose-finding, proof-of-concept study was conducted in Bolivia. Adults with serologically confirmed chronic indeterminate CD and positive PCR were randomly assigned to 1 of 6 fexinidazole regimens (1200 or 1800 mg\/day for 2, 4, or 8 weeks) or placebo. Target recruitment was 20 patients\/arm. The primary endpoint was sustained parasitological clearance by serial negative qPCR from end of treatment (EOT) until 6 months follow-up in the intention-to-treat (ITT) population. Follow-up was extended to 12 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Enrollment was interrupted after 4\/47 patients presented with transient asymptomatic grade 3 and 4 neutropenia. Treatment of ongoing patients was stopped in all patients administered &amp;gt;2 weeks. A total of 40 patients received treatment with fexinidazole from 3 days to 8 weeks. Delayed-onset neutropenia (n = 8) and increased liver enzymes (n = 8) were found in fexinidazole patients vs none in the placebo arm. In the ITT analysis, sustained parasitological clearance from EOT to 12 months follow-up varied between 66.7% (1200 mg\u20132 week) and 100.0% (1800 mg\u20132 week). Rapid, sustained clearance of parasitemia was observed in all treated patients with available data, but not in any patients in the placebo group, at 12 months (P = .0056). Further exploratory exposure-response analysis suggested low dosages of fexinidazole may be safe and effective.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Further evaluation is needed to establish fexinidazole\u2019s minimum effective dosage and risk\u2013benefit relationship. Results suggest potential for effective treatment regimens &amp;lt;10 days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trials Registration<\/jats:title>\n                    <jats:p>NCT02498782.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciac579","type":"journal-article","created":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T11:20:13Z","timestamp":1659612013000},"page":"e1186-e1194","source":"Crossref","is-referenced-by-count":46,"title":["A Phase 2, Randomized, Multicenter, Placebo-Controlled, Proof-of-Concept Trial of Oral Fexinidazole in Adults With Chronic Indeterminate Chagas Disease"],"prefix":"10.1093","volume":"76","author":[{"given":"Faustino","family":"Torrico","sequence":"first","affiliation":[{"name":"Universidad Mayor de San Sim\u00f3n and Fundaci\u00f3n CEADES , Cochabamba , Bolivia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquim","family":"Gasc\u00f3n","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal), Hospital Clinic-University of Barcelona; CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III (CIBERINFEC, ISCIII) , Barcelona , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lourdes","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Universidad Aut\u00f3noma Juan Misael Saracho de Tarija, Bolivia and Fundaci\u00f3n CEADES , Tarija , Bolivia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimy","family":"Pinto","sequence":"additional","affiliation":[{"name":"Universidad Mayor de San Sim\u00f3n and Fundaci\u00f3n CEADES , Cochabamba , Bolivia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gimena","family":"Rojas","sequence":"additional","affiliation":[{"name":"Universidad Mayor de San Sim\u00f3n and Fundaci\u00f3n CEADES , Cochabamba , Bolivia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Palacios","sequence":"additional","affiliation":[{"name":"Universidad Aut\u00f3noma Juan Misael Saracho de Tarija, Bolivia and Fundaci\u00f3n CEADES , Tarija , Bolivia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana","family":"Barreira","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases Initiative , Geneva , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bethania","family":"Blum","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases Initiative , Geneva , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro Gabriel","family":"Schijman","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda Molecular de la Enfermedad de Chagas, Instituto de Investigaciones en Ingenier\u00eda Gen\u00e9tica y Biolog\u00eda Molecular \u201cDr. H\u00e9ctor N. Torres\u201d\u2014INGEBI-CONICET , Buenos Aires , Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Vaillant","sequence":"additional","affiliation":[{"name":"Centre de Recherche Public de la Sant\u00e9 CRP-Sant\u00e9 , Strassen , Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Strub-Wourgaft","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases Initiative , Geneva , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Jesus","family":"Pinazo","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal), Hospital Clinic-University of Barcelona; CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III (CIBERINFEC, ISCIII) , Barcelona , Spain"},{"name":"Drugs for Neglected Diseases Initiative , Geneva , 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