{
  "abstract": "Introduction Glucocorticoid (GC) bridging therapy is recommended in patients with rheumatoid arthritis commencing a disease-modifying anti-rheumatic drug (DMARD). It is not clear whether GC therapy is better administered intramuscularly or orally and at what dose level. The aim of the LEADER trial is to identify the most effective and safest way of using steroids in patients with uncontrolled RA who are starting a DMARD.Methods and analysis A multicentre, randomised, open-label, four-arm, parallel-group clinical trial with an internal pilot phase, economic evaluation and qualitative study of acceptability. Participants will be randomised to one of four arms: arm A, 30 mg oral prednisolone tapering over 6 weeks; arm B, 15 mg oral prednisolone tapering over 4 weeks; arm C, Intramuscularly 120 mg methylprednisolone; and arm D, Intramuscularly 80 mg methylprednisolone. Participants will be assessed at baseline (pre-GC intervention), 4, 12 and 24 weeks. The primary outcome measure is the mean DAS(CRP)−28 over 12 weeks. The primary comparison will be according to route of administration (oral vs intramuscular GC treatment) with secondary comparisons within route of administration to provide evidence of dose effectiveness. Toxicity will be measured using the Glucocorticoid Toxicity Index, a clinical outcome assessment and early morning cortisol level. LEADER will be conducted in ~30 sites delivering NHS care, recruiting a sample size of 448. Economic evaluation will compare cost-effectiveness within a trial and over a lifetime horizon from the English National Health Service perspective.Ethics and dissemination The LEADER trial received MHRA and Leicester Central Research Ethics Committee ethics approval (REC reference: 24/EM/0277, IRAS 1010280), opened to recruitment on Protocol Version 4.0 and is currently recruiting on Protocol Version 5.0. Participants will provide written informed consent in accordance with the Declaration of Helsinki and applicable regulatory requirements. Trial results will be disseminated via presentations at national and international meetings, published in open-access journals and to patients.Trial registration number ISRCTN32090559.",
  "authors": [
    {
      "affiliations": [
        "Oxford Clinical Trials Research Unit, Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, England, UK"
      ],
      "name": "Jonathan Alistair Cook"
    },
    {
      "affiliations": [
        "Department of Rheumatology, King’s College Hospital NHS Foundation Trust, London, UK",
        "Centre for Rheumatic Diseases, Kings College London, London, England, UK"
      ],
      "name": "Nicky Wilson"
    },
    {
      "affiliations": [
        "Centre for Rheumatic Diseases, Kings College London, London, England, UK"
      ],
      "name": "Kate Wilkins"
    },
    {
      "affiliations": [
        "Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Division of Musculoskeletal & Dermatological Sciences, The University of Manchester, Manchester, UK"
      ],
      "name": "Karen Staniland"
    },
    {
      "affiliations": [
        "Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Division of Musculoskeletal & Dermatological Sciences, The University of Manchester, Manchester, UK"
      ],
      "name": "Iniobong Ekang"
    },
    {
      "affiliations": [
        "Diabetes, Endocrinology and Metabolism, Manchester University NHS Foundation Trust, Manchester, Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, England, UK"
      ],
      "name": "Shazli Azmi"
    },
    {
      "affiliations": [
        "Wellcome-Wolfson Institute for Experimental Medicine School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, Northern Ireland, UK"
      ],
      "name": "Liam Heaney"
    },
    {
      "affiliations": [
        "Manchester Centre for Health Economics, Division of Population Health, Health Services Research and Primary Care, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK"
      ],
      "name": "Sean P Gavan"
    },
    {
      "affiliations": [
        "Manchester Centre for Health Economics, Division of Population Health, Health Services Research and Primary Care, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK"
      ],
      "name": "Rachel Ann Elliott"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University College London Hospitals NHS Foundation Trust, London, UK"
      ],
      "name": "Robert J Wilson"
    },
    {
      "affiliations": [
        "Oxford Clinical Trials Research Unit, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, UK"
      ],
      "name": "Clare Calvert"
    },
    {
      "affiliations": [
        "Oxford Clinical Trials Research Unit, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, UK"
      ],
      "name": "Anne Francis"
    },
    {
      "affiliations": [
        "Oxford Clinical Trials Research Unit, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, UK"
      ],
      "name": "Jennifer Anne Elizabeth Williams"
    },
    {
      "affiliations": [
        "Oxford Clinical Trials Research Unit, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, UK"
      ],
      "name": "Anabella Turner"
    },
    {
      "affiliations": [
        "Oxford Clinical Trials Research Unit, Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, England, UK"
      ],
      "name": "Alex Zimmermann"
    },
    {
      "affiliations": [
        "Department of Medicine, University of Cambridge, Cambridge, UK"
      ],
      "name": "Duncan Richards"
    },
    {
      "affiliations": [
        "Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Division of Musculoskeletal & Dermatological Sciences, The University of Manchester, Manchester, UK",
        "NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester, England, UK"
      ],
      "name": "Anne Barton"
    },
    {
      "affiliations": [
        "Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Division of Musculoskeletal & Dermatological Sciences, The University of Manchester, Manchester, UK",
        "NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester, England, UK"
      ],
      "name": "James Bluett"
    },
    {
      "affiliations": [],
      "name": "The LEADER trial network"
    }
  ],
  "title": "Clinical and cost-effectiveness of oral versus intramuscular glucocorticoids in rheumatoid arthritis: protocol for a multicentre randomised controlled trial with economic evaluation and qualitative sub-study (LEADER trial)",
  "uid": "fb15b792-5c25-5b7f-9f69-bbb97b03de0a"
}