Evidence map›Paper›PMID 24454970›Full record

Trial reportPLoS neglected tropical diseases2014

Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa: a randomised trial.

Eltahir A G Khalil, Teklu Weldegebreal, Brima M Younis, Raymond Omollo, Ahmed M Musa, Workagegnehu Hailu, Abuzaid A Abuzaid, Thomas P C Dorlo, Zewdu Hurissa, Sisay Yifru and 10 more

Open access · goldAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in PLoS neglected tropical diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 4 pooled it
11.2field-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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 4 syntheses or guidelines pooled it, 100 citations in OpenAlex.

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  6. Blood Parasite Load as an Early Marker to Predict Treatment Response in Visceral Leishmaniasis in Eastern Africa.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021
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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

20 authors at 9 institutions in 6 countries.

Eltahir A G KhalilInstitute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
Teklu WeldegebrealArba Minch Hospital, Regional Health Bureau of SNNP State, Arba Minch, Ethiopia.
Brima M YounisInstitute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
Raymond OmolloDrugs for Neglected Diseases initiative (DNDi) Africa Regional Office, Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya.
Ahmed M MusaInstitute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
Workagegnehu HailuUniversity of Gondar, College of Medicine & Health Sciences, Gondar, Ethiopia.
Abuzaid A AbuzaidInstitute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
Thomas P C DorloAcademic Medical Center, University of Amsterdam, Amsterdam, The Netherlands ; Slotervaart Hospital/The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Zewdu HurissaUniversity of Gondar, College of Medicine & Health Sciences, Gondar, Ethiopia.
Sisay YifruUniversity of Gondar, College of Medicine & Health Sciences, Gondar, Ethiopia.
William HalekeArba Minch Hospital, Regional Health Bureau of SNNP State, Arba Minch, Ethiopia.
Peter G SmithMRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Sally EllisDrugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
Manica BalasegaramDrugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
Ahmed M EL-HassanInstitute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
Gerard J SchooneRoyal Tropical Institute, KIT Biomedical Research, Amsterdam, The Netherlands.
Monique WasunnaDrugs for Neglected Diseases initiative (DNDi) Africa Regional Office, Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya ; Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya.
Robert KimutaiDrugs for Neglected Diseases initiative (DNDi) Africa Regional Office, Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya ; Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya.
Tansy EdwardsMRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Asrat HailuSchool of Medicine, Addis Ababa University, Addis Ababa, Ethiopia.
University of Khartoum · SDKenya Medical Research Institute · KEUniversity of Gondar · ETArba Minch University · ETDrugs for Neglected Diseases Initiative · CHLondon School of Hygiene & Tropical Medicine · GBAddis Ababa University · ETRoyal Tropical Institute · NLSlotervaartziekenhuis · NL

Funding

Medical Research Council MR/K012126/1
6 · The paper itself

Abstract

backgroundAnti-leishmanial drug regimens that include a single dose AmBisome could be suitable for eastern African patients with symptomatic visceral leishmaniasis (VL) but the appropriate single dose is unknown. METHODOLOGY: A multi-centre, open-label, non-inferiority, randomized controlled trial with an adaptive design, was conducted to compare the efficacy and safety of a single dose and multiple doses of AmBisome for the treatment of VL in eastern Africa. The primary efficacy endpoint was definitive cure (DC) at 6 months. Symptomatic patients with parasitologically-confirmed, non-severe VL, received a single dose of AmBisome 7.5 mg/kg body weight or multiple doses, 7 times 3 mg/kg on days 1-5, 14, and 21. If interim analyses, evaluated 30 days after the start of treatment following 40 or 80 patients, showed the single dose gave significantly poorer parasite clearance than multiple doses at the 5% significance level, the single dose was increased by 2·5 mg/kg. In a sub-set of patients, parasite clearance was measured by quantitative reverse transcriptase (qRT) PCR. PRINCIPAL

findingsThe trial was terminated after the third interim analysis because of low efficacy of both regimens. Based on the intention-to-treat population, DC was 85% (95%CI 73-93%), 40% (95%CI 19-64%), and 58% (95%CI 41-73%) in patients treated with multiple doses (n = 63), and single doses of 7·5 (n = 21) or 10 mg/kg (n = 40), respectively. qRT-PCR suggested superior parasite clearance with multiple doses as early as day 3. Safety data accorded with the drug label.

conclusionsThe tested AmBisome regimens would not be suitable for VL treatment across eastern Africa. An optimal single dose regimen was not identified. TRIALS REGISTRATION: www.clinicaltrials.govNCT00832208.

Indexed as

AdolescentAdultAfrica, EasternAmphotericin BAntiprotozoal AgentsChildChild, PreschoolDrug-Related Side Effects and Adverse ReactionsFemaleHumansLeishmaniasis, VisceralMaleParasite LoadReal-Time Polymerase Chain ReactionTreatment OutcomeYoung AdultAmphotericin BAntiprotozoal Agentsliposomal amphotericin B

Identifiers

PMID24454970
PMCPMC3894173
OpenAlexW2123082391

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.