ArticlePloS one2017
Defining Surrogate Endpoints for Clinical Trials in Severe Falciparum Malaria.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Outcomes reported in trials of treatments for severe malaria: The need for a core outcome set.Tropical medicine & international health : TM & IH · 2022Pooled it
- Defining the next generation of severe malaria treatment: a target product profile.Malaria journal · 2024Review
- Post hospital admission blood lactate measurements are associated with mortality but not neurologic morbidity in children with cerebral malaria.Malaria journal · 2024Article
- SEVUparin as a potential Adjunctive Treatment in children with severe malaria: A phase I trial safety and dose finding trial (SEVUSMAART).Wellcome open research · 2023Article
- The assessment of antimalarial drug efficacy in vivo.Trends in parasitology · 2022Review
- Alteration of Blood Lactate Levels in Severe Falciparum Malaria: A Systematic Review and Meta-Analysis.Biology · 2021Review
- Clinical trials to assess adjuvant therapeutics for severe malaria.Malaria journal · 2020Article
- Associations Between Restrictive Fluid Management and Renal Function and Tissue Perfusion in Adults With Severe Falciparum Malaria: A Prospective Observational Study.The Journal of infectious diseases · 2020Observational
- Severe malaria management: current situation, challenges and lessons learned from Gezira State, Sudan.Malaria journal · 2019Article
- Identifying the Components of Acidosis in Patients With Severe Plasmodium falciparum Malaria Using Metabolomics.The Journal of infectious diseases · 2019Observational
- Lactate clearance as a prognostic marker of mortality in severely ill febrile children in East Africa.BMC medicine · 2018Article
- Adjunctive therapy for severe malaria: a review and critical appraisal.Malaria journal · 2018Review
- malERA: An updated research agenda for diagnostics, drugs, vaccines, and vector control in malaria elimination and eradication.PLoS medicine · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 3 institutions in 6 countries.
Funding
Abstract
backgroundClinical trials in severe falciparum malaria require a large sample size to detect clinically meaningful differences in mortality. This means few interventions can be evaluated at any time. Using a validated surrogate endpoint for mortality would provide a useful alternative allowing a smaller sample size. Here we evaluate changes in coma score and plasma lactate as surrogate endpoints for mortality in severe falciparum malaria.
methodsThree datasets of clinical studies in severe malaria were re-evaluated: studies from Chittagong, Bangladesh (adults), the African 'AQUAMAT' trial comparing artesunate and quinine (children), and the Vietnamese 'AQ' study (adults) comparing artemether with quinine. The absolute change, relative change, slope of the normalization over time, and time to normalization were derived from sequential measurements of plasma lactate and coma score, and validated for their use as surrogate endpoint, including the proportion of treatment effect on mortality explained (PTE) by these surrogate measures.
resultsImprovements in lactate concentration or coma scores over the first 24 hours of admission, were strongly prognostic for survival in all datasets. In hyperlactataemic patients in the AQ study (n = 173), lower mortality with artemether compared to quinine closely correlated with faster reduction in plasma lactate concentration, with a high PTE of the relative change in plasma lactate at 8 and 12 hours of 0.81 and 0.75, respectively. In paediatric patients enrolled in the 'AQUAMAT' study with cerebral malaria (n = 785), mortality was lower with artesunate compared to quinine, but this was not associated with faster coma recovery.
conclusionsThe relative changes in plasma lactate concentration assessed at 8 or 12 hours after admission are valid surrogate endpoints for severe malaria studies on antimalarial drugs or adjuvant treatments aiming at improving the microcirculation. Measures of coma recovery are not valid surrogate endpoints for mortality.
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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 Socratic graph.