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Cited by 1Gout, Hyperuricemia, Uric AcidStatistical Methods in Clinical TrialsMusculoskeletal pain and rehabilitation

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Prednisolone Versus Colchicine for Acute Gout in Primary Care: statistical analysis plan for the pragmatic, multicenter, randomized, and double-blinded COPAGO non-inferiority trial

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Richter, Adrian, Truthmann, Julia, Hummers, Eva, Pereira, Julia Freyer Martins, Gágyor, Ildikó, Schuster, Franziska, Witte, Amelie, Böhm, Susanne, Greser, Alexandra, Kamin, Petra, Stracke, Sylvia, Dörr, Marcus, Bülow, Robin, Engeli, Stefan, Chenot, Jean François, Ittermann, Till·2024·Trials
DOI 10.1186/s13063-024-08066-0PMC PMC10988876

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Abstract

Background: To date, colchicine and prednisolone are two effective therapies for the treatment of acute gout but have never been compared directly in a randomized clinical trial. In addition, in previous trials of treating acute gout patients with concomitant comorbidities were often excluded due to contraindications to naproxen. Study design: This pragmatic, prospective, double-blind, double-dummy, parallel-group, randomized, non-inferiority trial compares prednisolone with colchicine in terms of non-inferiority in patients with acute gout. Patients presenting to their general practitioner with acute gout can be included if the gout attack has occurred within the last 2 days. A total of 60 practices in the vicinity of three university medical centers (Greifswald, Göttingen, and Würzburg) participate in the study. The intervention group receives 30 mg prednisolone for 5 days, while the group of standard care receives low-dose colchicine (day 1: 1.5 mg; days 2–5: 1 mg). The first dose of treatment is provided at day 0 when patients present to the general practitioner due to an acute gout attack. From day 0 to day 6, patients will be asked to complete a study diary on daily basis regarding pain quantification. For safety reasons, potential side effects and the course of systolic blood pressure are also assessed. Statistical analysis plan: N = 314 patients have to be recruited to compensate for 10% of dropout and to allow for showing non-inferiority of prednisolone compared to colchicine with a power of 90%. We use permuted block randomization with block sizes of 2, 4, and 6 to avoid imbalanced treatment arms in this multi-center study; patients are randomized in a 1:1 ratio. The absolute level of pain on day 3 (in the last 24 h) is the primary outcome and measured on a numerical rating scale (NRS: 0–10). Using a multiple linear regression model adjusted for age, sex, and pain at baseline, prednisolone is considered non-inferior if the effect estimate including the confidence intervals is lower than a margin of 1 unit on the NRS. Average response to treatment, joint swelling and tenderness, physical function of the joint, and patients’ global assessment of treatment success are secondary outcomes. Discussion: The trial will provide evidence from a direct comparison of colchicine and prednisolone regarding their efficacy of pain reduction in acute gout patients of primary care and to indicate possible safety signals. Trial registration: ClinicalTrials.gov Identifier: NCT05698680 first posted on January 26, 2023 (retrospectively registered).

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Metadata

Authors
Richter, A., Truthmann, J., Hummers, E., Pereira, J. F. M., Gágyor, I., Schuster, F., Witte, A., Böhm, S., Greser, A., Kamin, P., Stracke, S., Dörr, M., Bülow, R., Engeli, S., Chenot, J. F., & Ittermann, T.
Affiliations
  • Universitätsmedizin Greifswald (DE)
  • Universitätsmedizin Göttingen (DE)
  • Universitätsklinikum Würzburg (DE)
Corresponding author
Richter, Adrian
ORCID
Venue
Trials
Publisher
Springer Science and Business Media LLC
Published
2024-04-03
Volume
25
Issue
1
Pages
229-229
ISSN
1745-6215 (ISSN-L)
DOI
10.1186/s13063-024-08066-0
PMC
PMC10988876
OpenAlex
W4393900285
Cited by
1
References
2
Citations by year
2025: 1
FWCI
0.28
Type
journal article
Language
en
Open access
Licence
Locations
  • Trials (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PUBLISSO (German National Library of Medicine) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
Funders
  • Bundesministeriums für Bildung und Forschung (01KG2022)
  • Universitätsmedizin Greifswald
Topics
  • Health Sciences › Medicine › Nephrology › Gout, Hyperuricemia, Uric Acid
  • Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
  • Health Sciences › Health Professions › Physical Therapy, Sports Therapy and Rehabilitation › Musculoskeletal pain and rehabilitation
Keywords
gout flares, prednisolone, colchicine, non-inferiority, pain assessment, numerical rating scale, joint swelling and tenderness, physical function, corticosteroids, primary care, statistical analysis plan, sample size determination, multiple linear regression, comorbidities, systolic blood pressure
MeSH terms
Colchicine, Female, Gout, Humans, Male, Pain, Prednisolone, Primary Health Care, Prospective Studies, Arthritis, Gouty, Treatment Outcome

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