Paromomycin and Miltefosine Combination as an Alternative to Treat Patients With Visceral Leishmaniasis in Eastern Africa: A Randomized, Controlled, Multicountry Trial. (27th September 2022)

• Record Type: Journal Article
• Authors: Musa, Ahmed M; Mbui, Jane; Mohammed, Rezika; Olobo, Joseph; Ritmeijer, Koert; Alcoba, Gabriel; Muthoni Ouattara, Gina; Egondi, Thaddaeus; Nakanwagi, Prossy; Omollo, Truphosa; Wasunna, Monique; Verrest, Luka; Dorlo, Thomas P C; Musa Younis, Brima; Nour, Ali; Taha Ahmed Elmukashfi, Elmukashfi; Ismail Omer Haroun, Ahmed; Khalil, Eltahir A G; Njenga, Simon; Fikre, Helina; Mekonnen, Tigist; Mersha, Dagnew; Sisay, Kasaye; Sagaki, Patrick; Alvar, Jorge; Solomos, Alexandra; Alves, Fabiana
• Is Part Of: Clinical infectious diseases. Volume 76:Number 3(2023)
• Page Start: e1177
• Page End: e1185
• Publication Date: 2022-09-27
• Subjects: visceral leishmaniasis -- phase 3 trial -- miltefosine -- paromomycin -- eastern Africa; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciac643
• Languages: English
• ISSNs: 1058-4838

Abstract

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 : With 1 fewer injection each day, shorter treatment duration, and no risk of sodium stibogluconate–associated cardiotoxicity, paromomycin plus miltefosine is a more patient-friendly alternative to sodium stibogluconate plus paromomycin for children and adults with visceral leishmaniasis in eastern Africa.