LogoLogoMSF Science Portal
  • My saved items
logo

© Médecins Sans Frontières

MSF Science Portal
About MSF Science Portal
About MSF
Contact Us
Frequently Asked Questions (FAQs)
Privacy Policy
Terms of Use

v2.1.4829.produseast1

Journal Article > Research

Paromomycin and miltefosine combination as an alternative to treat patients with visceral leishmaniasis in Eastern Africa: A randomized, controlled, multicountry trial

Musa AM, Mbui J, Mohammed R, Olobo J, Ritmeijer KKD, Alcoba G, Muthoni Ouattara G, Egondi T, Nakanwagi P, Omollo T, Wasunna M, Verrest L, Dorlo TPC, Musa Younis B, Nour AB, Taha Ahmed Elmukashfi E, Ismail Omer Haroun A, Khalil EAG, Njenga SN, Fikre H, Mekonnen T, Mersha D, Sisay K, Sagaki P, Alvar J, Solomos A, Alves F
Download
Download
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.
Countries
EthiopiaKenyaUgandaSudan
Subject Area
neglected tropical diseaseskala azar
Collections
World NTD Day
DOI
10.1093/cid/ciac643
Published Date
27-Sep-2022
PubMed ID
36164254
Languages
English
Journal
Clinical Infectious Diseases
Volume / Issue / Pages
Volume Online ahead of print, Pages ciac643
Dimensions Badge