Evidence map›Paper›PMID 36164254›Full record

Trial reportClinical infectious diseases : an official publication of the Infectious Diseases Society of America2023

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

Ahmed M Musa, Jane Mbui, Rezika Mohammed, Joseph Olobo, Koert Ritmeijer, Gabriel Alcoba, Gina Muthoni Ouattara, Thaddaeus Egondi, Prossy Nakanwagi, Truphosa Omollo and 17 more

Registry-linked trialOpen access · bronzeAbstract readRandomized Controlled TrialClinical Trial, Phase III
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03129646 (An Open Label, Phase III, Randomized Controlled, Multicentre Non-Inferiority Trial to Compare Efficacy and Safety of Miltefosine and Paromomycin With SSG and PM Combination for Treatment of Primary Visceral Leishmaniasis), which is not on this map. Cited by 33 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 3 pooled it
12.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03129646 phase3completednot on this map

An Open Label, Phase III, Randomized Controlled, Multicentre Non-Inferiority Trial to Compare Efficacy and Safety of Miltefosine and Paromomycin With SSG and PM Combination for Treatment of Primary Visceral Leishmaniasis (VL) Patients in Eastern Africa

TypeinterventionalSponsorDrugs for Neglected DiseasesRan2018 to 2020Enrolled439ConditionsVisceral LeishmaniasisArmsMiltefosine, Paromomycin, Sodium stibogluconate
3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 3 syntheses or guidelines pooled it, 67 citations in OpenAlex.

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  11. Leishmaniasis.Nature reviews. Disease primers · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors at 10 institutions in 6 countries.

Ahmed M MusaInstitute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
Jane MbuiCentre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya.
Rezika MohammedLeishmaniasis Research and Treatment Center, University of Gondar, Gondar, Ethiopia.
Joseph OloboDepartment of Immunology and Molecular Biology, Leishmaniasis Unit, College of Health Sciences, Makerere University, Kampala, Uganda.
Koert RitmeijerMédecins sans Frontières, OCA, Amsterdam, The Netherlands.
Gabriel AlcobaMédecins sans Frontières, OCG, Geneva, Switzerland.
Gina Muthoni OuattaraDrugs for Neglected Diseases Initiative, Nairobi, Kenya.
Thaddaeus EgondiDrugs for Neglected Diseases Initiative, Nairobi, Kenya.
Prossy NakanwagiDrugs for Neglected Diseases Initiative, Nairobi, Kenya.
Truphosa OmolloDrugs for Neglected Diseases Initiative, Nairobi, Kenya.
Monique WasunnaDrugs for Neglected Diseases Initiative, Nairobi, Kenya.
Luka VerrestDepartment of Pharmacy & Pharmacology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Thomas P C DorloDepartment of Pharmacy & Pharmacology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Brima Musa YounisInstitute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
Ali NourInstitute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
Elmukashfi Taha Ahmed ElmukashfiInstitute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
Ahmed Ismail Omer HarounInstitute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
Eltahir A G KhalilInstitute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
Simon NjengaCentre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya.
Helina FikreLeishmaniasis Research and Treatment Center, University of Gondar, Gondar, Ethiopia.
Tigist MekonnenLeishmaniasis Research and Treatment Center, University of Gondar, Gondar, Ethiopia.
Dagnew MershaMédecins sans Frontières, Abdurafi, Ethiopia.
Kasaye SisayMédecins sans Frontières, Abdurafi, Ethiopia.
Patrick SagakiAmudat Hospital, Amudat Karamoja Sub-region, Uganda.
Jorge AlvarDrugs for Neglected Diseases Initiative, Geneva, Switzerland.
Alexandra SolomosDrugs for Neglected Diseases Initiative, Geneva, Switzerland.
Fabiana AlvesDrugs for Neglected Diseases Initiative, Geneva, Switzerland.
University of Khartoum · SDKenya AIDS Vaccine Initiative · KEDrugs for Neglected Diseases Initiative · CHUniversity of Gondar · ETKenya Medical Research Institute · KEMédecins Sans Frontières · UGThe Netherlands Cancer Institute · NLMakerere University · UGMédecins Sans Frontières · CHMédecins Sans Frontières · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThis 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.

methodsAn 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.

resultsOf 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.

conclusionsPM/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.

Indexed as

Antiprotozoal AgentsLeishmaniasis, VisceralAdultAfrica, EasternAntimony Sodium GluconateChildDrug Therapy, CombinationHumansParomomycinPhosphorylcholineTreatment OutcomeAntimony Sodium GluconateAntiprotozoal AgentsmiltefosineParomomycinPhosphorylcholineeastern Africamiltefosineparomomycinphase 3 trialvisceral leishmaniasis

Identifiers

PMID36164254
PMCPMC9907539
OpenAlexW4297252423

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.