{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:05:40Z","timestamp":1792076740098,"version":"4.4.0"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T00:00:00Z","timestamp":1664236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001713","name":"European and Developing Countries Clinical Trials Partnership","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001713","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007729","name":"Dutch Ministry of Foreign Affairs","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007729","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":"Medicor Foundation"},{"name":"M\u00e9decins sans Fronti\u00e8res International,"},{"DOI":"10.13039\/100009131","name":"Swiss Agency for Development and Cooperation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100009131","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003246","name":"Dutch Research Council","doi-asserted-by":"crossref","award":["91617140"],"award-info":[{"award-number":["91617140"]}],"id":[{"id":"10.13039\/501100003246","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>This study aimed to determine whether paromomycin plus miltefosine (PM\/MF) is noninferior to sodium stibogluconate plus paromomycin (SSG\/PM) for treatment of primary visceral leishmaniasis in eastern Africa.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An open-label, phase 3, randomized, controlled trial was conducted in adult and pediatric patients at 7 sites in eastern Africa. Patients were randomly assigned to either 20 mg\/kg paromomycin plus allometric dose of miltefosine (14 days), or 20 mg\/kg sodium stibogluconate plus 15 mg\/kg paromomycin (17 days). The primary endpoint was definitive cure after 6 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 439 randomized patients, 424 completed the trial. Definitive cure at 6 months was 91.2% (155 of 170) and 91.8% (156 of 170) in the PM\/MF and SSG\/PM arms in primary efficacy modified intention-to-treat analysis (difference, 0.6%; 97.5% confidence interval [CI], \u22126.2 to 7.4), narrowly missing the noninferiority margin of 7%. In the per-protocol analysis, efficacy was 92% (149 of 162) and 91.7% (155 of 169) in the PM\/MF and SSG\/PM arms (difference, \u22120.3%; 97.5% CI, \u20137.0 to 6.5), demonstrating noninferiority. Treatments were well tolerated. Four of 18 serious adverse events were study drug\u2013related, and 1 death was SSG-related. Allometric dosing ensured similar MF exposure in children (&amp;lt;12 years) and adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PM\/MF and SSG\/PM efficacies were similar, and adverse drug reactions were as expected given the drugs safety profiles. With 1 less injection each day, reduced treatment duration, and no risk of SSG-associated life-threatening cardiotoxicity, PM\/MF is a more patient-friendly alternative for children and adults with primary visceral leishmaniasis in eastern Africa.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trials Registration<\/jats:title>\n                    <jats:p>NCT03129646.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciac643","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T08:12:40Z","timestamp":1661760760000},"page":"e1177-e1185","source":"Crossref","is-referenced-by-count":56,"title":["Paromomycin and Miltefosine Combination as an Alternative to Treat Patients With Visceral Leishmaniasis in Eastern Africa: A Randomized, Controlled, Multicountry Trial"],"prefix":"10.1093","volume":"76","author":[{"given":"Ahmed M","family":"Musa","sequence":"first","affiliation":[{"name":"Institute of Endemic Diseases, University of Khartoum , Khartoum , Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Mbui","sequence":"additional","affiliation":[{"name":"Centre for Clinical Research, Kenya Medical Research Institute , Nairobi , Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rezika","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Leishmaniasis Research and Treatment Center, University of Gondar , Gondar , Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Olobo","sequence":"additional","affiliation":[{"name":"Department of Immunology and Molecular Biology, Leishmaniasis Unit, College of Health Sciences, Makerere University , Kampala , 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