Paromomycin and Miltefosine Combination as an Alternative to Treat Patients With Visceral Leishmaniasis in Eastern Africa: A Randomized, Controlled, Multicountry Trial.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2023 Feb 08

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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. 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. 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. 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. NCT03129646. © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Citation

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. Paromomycin and Miltefosine Combination as an Alternative to Treat Patients With Visceral Leishmaniasis in Eastern Africa: A Randomized, Controlled, Multicountry Trial. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2023 Feb 08;76(3):e1177-e1185