학술논문
Paromomycin and Miltefosine Combination as an Alternative to Treat Patients With Visceral Leishmaniasis in Eastern Africa: A Randomized, Controlled, Multicountry Trial.
Document Type
Article
Author
Musa, Ahmed M; Mbui, Jane; Mohammed, Rezika; Olobo, Joseph; Ritmeijer, Koert; Alcoba, Gabriel; Ouattara, Gina Muthoni; Egondi, Thaddaeus; Nakanwagi, Prossy; Omollo, Truphosa; Wasunna, Monique; Verrest, Luka; Dorlo, Thomas P C; Younis, Brima Musa; Nour, Ali; Elmukashfi, Elmukashfi Taha Ahmed; Haroun, Ahmed Ismail Omer; Khalil, Eltahir A G; Njenga, Simon; Fikre, Helina
Source
Subject
*ANTIPROTOZOAL agents
*RESEARCH
*LEISHMANIASIS
*COMBINATION drug therapy
*CONFIDENCE intervals
*MULTIVARIATE analysis
*NEOMYCIN
*TREATMENT effectiveness
*RANDOMIZED controlled trials
*MILTEFOSINE
*DESCRIPTIVE statistics
*DATA analysis software
*LOGISTIC regression analysis
*PHARMACODYNAMICS
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Language
ISSN
1058-4838
Abstract
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 (<12 years) and adults. 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. [ABSTRACT FROM AUTHOR]