학술논문
Paromomycin and Miltefosine Combination as an Alternative to Treat Patients With Visceral Leishmaniasis in Eastern Africa: A Randomized, Controlled, Multicountry Trial.
Document Type
Academic Journal
Author
Musa AM; Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.; Mbui J; Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya.; Mohammed R; Leishmaniasis Research and Treatment Center, University of Gondar, Gondar, Ethiopia.; Olobo J; Department of Immunology and Molecular Biology, Leishmaniasis Unit, College of Health Sciences, Makerere University, Kampala, Uganda.; Ritmeijer K; Médecins sans Frontières, OCA, Amsterdam, The Netherlands.; Alcoba G; Médecins sans Frontières, OCG, Geneva, Switzerland.; Muthoni Ouattara G; Drugs for Neglected Diseases Initiative, Nairobi, Kenya.; Egondi T; Drugs for Neglected Diseases Initiative, Nairobi, Kenya.; Nakanwagi P; Drugs for Neglected Diseases Initiative, Nairobi, Kenya.; Omollo T; Drugs for Neglected Diseases Initiative, Nairobi, Kenya.; Wasunna M; Drugs for Neglected Diseases Initiative, Nairobi, Kenya.; Verrest L; Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.; Dorlo TPC; Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.; Musa Younis B; Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.; Nour A; Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.; Taha Ahmed Elmukashfi E; Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.; Ismail Omer Haroun A; Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.; Khalil EAG; Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.; Njenga S; Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya.; Fikre H; Leishmaniasis Research and Treatment Center, University of Gondar, Gondar, Ethiopia.; Mekonnen T; Leishmaniasis Research and Treatment Center, University of Gondar, Gondar, Ethiopia.; Mersha D; Médecins sans Frontières, Abdurafi, Ethiopia.; Sisay K; Médecins sans Frontières, Abdurafi, Ethiopia.; Sagaki P; Amudat Hospital, Amudat Karamoja Sub-region, Uganda.; Alvar J; Drugs for Neglected Diseases Initiative, Geneva, Switzerland.; Solomos A; Drugs for Neglected Diseases Initiative, Geneva, Switzerland.; Alves F; Drugs for Neglected Diseases Initiative, Geneva, Switzerland.
Source
Publisher: Oxford University Press Country of Publication: United States NLM ID: 9203213 Publication Model: Print Cited Medium: Internet ISSN: 1537-6591 (Electronic) Linking ISSN: 10584838 NLM ISO Abbreviation: Clin Infect Dis Subsets: MEDLINE
Subject
Language
English
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.
Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
(© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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.
Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
(© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)