{
  "abstract": "Mortality rates for African children with severe malaria remain high. Sevuparin, a heparin-like compound, as an adjunctive treatment, may improve outcomes due to its effects on Plasmodium falciparum -infected erythrocytes. A Phase I dose-finding trial in Kenyan and Zambian children with severe malaria aimed to identify the maximum tolerated dose (MTD) of sevuparin, given as three infusions (at 0, 8 and 16 h post-enrolment) using the continual reassessment method (ISRCTN32271864). The primary endpoint was dose limiting toxicity (DLT) defined as Activated Partial Thromboplastin Time (APTT) > 95 seconds (2.5x upper limit of normal) across 1.5-6 mg/kg doses. Secondary endpoints were lactate clearance, parasite half-life, APTT at 24 h and grade 3-4 serious adverse events. Twenty-three children were enroled; 20 were included in the primary analysis, across 10 cohorts. A data monitoring committee followed model recommendations, leading to dose escalation from 1.5 mg/kg through all doses to 6 mg/kg when 2 DLTs occurred. During de-escalation, DLTs occurred at 5 mg/kg and 4 mg/kg. The final dose was therefore 3 mg/kg. There was 1 death (1/23 (4.3%)), 1 readmission and 1 grade 3 non-DLT adverse event: all judged unrelated to sevuparin. MTD of 3 mg/kg sevuparin in each of three infusions at 0, 8 and 16 h was identified for future investigation.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "Mike Chaponda"
    },
    {
      "name": "Jonathan Gwasupika"
    },
    {
      "name": "Roisin Connon",
      "orcid": "0000-0002-4408-4336"
    },
    {
      "name": "Patrick Tshilab Kabwit"
    },
    {
      "name": "Sam Miti"
    },
    {
      "name": "Nchafatso Obonyo",
      "orcid": "0000-0002-5040-4359"
    },
    {
      "name": "Diana M. Gibb"
    },
    {
      "name": "Thomas N. Williams"
    },
    {
      "name": "Nicholas P. J. Day"
    },
    {
      "name": "Arjen M. Dondorp",
      "orcid": "0000-0001-5190-2395"
    },
    {
      "name": "A. Sarah Walker"
    },
    {
      "name": "Elizabeth C. George",
      "orcid": "0000-0002-2928-3580"
    },
    {
      "name": "Kathryn Maitland",
      "orcid": "0000-0002-0007-0645"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a7snmb4d8yxpw.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-78536-3",
  "fulltext_url": "https://europepmc.org/articles/PMC13686957",
  "id": "a7snmb4d8yxpw",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://www.nature.com/articles/s41467-026-78536-3",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2739|Malaria Research and Control"
    ]
  ],
  "openalex": "W7165169146",
  "pdf_url": "https://www.nature.com/articles/s41467-026-78536-3.pdf",
  "pmcid": "PMC13686957",
  "pmid": "42907487",
  "published": "2026-10-21",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/a7snmb4d8yxpw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:39Z",
      "native_id": "10.1038/s41467-026-78536-3",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s41467-026-78536-3"
    },
    {
      "first_seen": "2026-10-30T12:19:53Z",
      "native_id": "MED:42907487",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42907487"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2739|Malaria Research and Control",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Sevuparin in children with severe malaria: a phase I safety and dose-finding trial",
  "title_text": "Sevuparin in children with severe malaria: a phase I safety and dose-finding trial",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:53Z",
  "url": "https://research.draconitic.com/paper/a7snmb4d8yxpw",
  "venue": "Nature Communications",
  "versions": []
}