Paromomycin and Miltefosine Combination as an Alternative to Treat Patients With Visceral Leishmaniasis in Eastern Africa: A Randomized, Controlled, Multicountry Trial
| العنوان: | Paromomycin and Miltefosine Combination as an Alternative to Treat Patients With Visceral Leishmaniasis in Eastern Africa: A Randomized, Controlled, Multicountry Trial |
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| المؤلفون: | Ahmed M, Musa, Jane, Mbui, Rezika, Mohammed, Joseph, Olobo, Koert, Ritmeijer, Gabriel, Alcoba, Gina, Muthoni Ouattara, Thaddaeus, Egondi, Prossy, Nakanwagi, Truphosa, Omollo, Monique, Wasunna, Luka, Verrest, Thomas P C, Dorlo, Brima, Musa Younis, Ali, Nour, Elmukashfi, Taha Ahmed Elmukashfi, Ahmed, Ismail Omer Haroun, Eltahir A G, Khalil, Simon, Njenga, Helina, Fikre, Tigist, Mekonnen, Dagnew, Mersha, Kasaye, Sisay, Patrick, Sagaki, Jorge, Alvar, Alexandra, Solomos, Fabiana, Alves |
| المصدر: | Clinical Infectious Diseases. 76:e1177-e1185 |
| بيانات النشر: | Oxford University Press (OUP), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Microbiology (medical), Infectious Diseases |
| الوصف: | Background 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. Methods 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. Results 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], −6.2 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, −0.3%; 97.5% CI, –7.0 to 6.5), demonstrating noninferiority. Treatments were well tolerated. Four of 18 serious adverse events were study drug–related, and 1 death was SSG-related. Allometric dosing ensured similar MF exposure in children ( Conclusions 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. Clinical Trials Registration NCT03129646. |
| تدمد: | 1537-6591 1058-4838 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bfe571622e1e72782a5232658c426563Test https://doi.org/10.1093/cid/ciac643Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....bfe571622e1e72782a5232658c426563 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15376591 10584838 |
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