Open-label randomised pragmatic trial (CONTACT) comparing naproxen and low-dose colchicine for the treatment of gout flares in primary care

Edward Roddy, Kris Clarkson, Milica Blagojevic-Bucknall, Rajnikant Mehta, Raymond Oppong, Anthony Avery, Elaine M Hay, Carl Heneghan, Liz Hartshorne, Julie Hooper, Gemma Hughes, Sue Jowett, Martyn Lewis, Paul Little, Karen McCartney, Kamal R Mahtani, David Nunan, Miriam Santer, Sam Williams, Christian D Mallen, Edward Roddy, Kris Clarkson, Milica Blagojevic-Bucknall, Rajnikant Mehta, Raymond Oppong, Anthony Avery, Elaine M Hay, Carl Heneghan, Liz Hartshorne, Julie Hooper, Gemma Hughes, Sue Jowett, Martyn Lewis, Paul Little, Karen McCartney, Kamal R Mahtani, David Nunan, Miriam Santer, Sam Williams, Christian D Mallen

Abstract

Objectives: To compare the effectiveness and safety of naproxen and low-dose colchicine for treating gout flares in primary care.

Methods: This was a multicentre open-label randomised trial. Adults with a gout flare recruited from 100 general practices were randomised equally to naproxen 750 mg immediately then 250 mg every 8 hours for 7 days or low-dose colchicine 500 mcg three times per day for 4 days. The primary outcome was change in worst pain intensity in the last 24 hours (0-10 Numeric Rating Scale) from baseline measured daily over the first 7 days: mean change from baseline was compared between groups over days 1-7 by intention to treat.

Results: Between 29 January 2014 and 31 December 2015, we recruited 399 participants (naproxen n=200, colchicine n=199), of whom 349 (87.5%) completed primary outcome data at day 7. There was no significant between-group difference in average pain-change scores over days 1-7 (colchicine vs naproxen: mean difference -0.18; 95% CI -0.53 to 0.17; p=0.32). During days 1-7, diarrhoea (45.9% vs 20.0%; OR 3.31; 2.01 to 5.44) and headache (20.5% vs 10.7%; 1.92; 1.03 to 3.55) were more common in the colchicine group than the naproxen group but constipation was less common (4.8% vs 19.3%; 0.24; 0.11 to 0.54).

Conclusion: We found no difference in pain intensity over 7 days between people with a gout flare randomised to either naproxen or low-dose colchicine. Naproxen caused fewer side effects supporting naproxen as first-line treatment for gout flares in primary care in the absence of contraindications.

Trial registration number: ISRCTN (69836939), clinicaltrials.gov (NCT01994226), EudraCT (2013-001354-95).

Keywords: colchicine; gout; naproxen; primary care; randomised trial.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1
Figure 1
Participant flow. CTU, Clinical Trials Unit. ITT, intention-to-treat.
Figure 2
Figure 2
Comparison of pain scores (primary outcome measure) at follow-up (intention-to-treat analysis).

References

    1. Kuo C-F, Grainge MJ, Mallen C, et al. . Rising burden of gout in the UK but continuing suboptimal management: a nationwide population study. Ann Rheum Dis 2015;74:661–7. 10.1136/annrheumdis-2013-204463
    1. Juraschek SP, Miller ER, Gelber AC. Body mass index, obesity, and prevalent gout in the United States in 1988-1994 and 2007-2010. Arthritis Care Res 2013;65:127–32. 10.1002/acr.21791
    1. Hui M, Carr A, Cameron S, et al. . The British Society for rheumatology guideline for the management of gout. Rheumatology 2017;56:1056–9. 10.1093/rheumatology/kex150
    1. Khanna D, Fitzgerald JD, Khanna PP, et al. . 2012 American College of rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res 2012;64:1431–46. 10.1002/acr.21772
    1. Richette P, Doherty M, Pascual E, et al. . 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis 2017;76:29–42. 10.1136/annrheumdis-2016-209707
    1. Sutaria S, Katbamna R, Underwood M. Effectiveness of interventions for the treatment of acute and prevention of recurrent gout—a systematic review. Rheumatology 2006;45:1422–31. 10.1093/rheumatology/kel071
    1. van Durme CMPG, Wechalekar MD, Buchbinder R, et al. . Non-Steroidal anti-inflammatory drugs for acute gout. Cochrane Database Syst Rev 2014:CD010120 10.1002/14651858.CD010120.pub2
    1. Roddy E, Mallen CD, Hider SL, et al. . Prescription and comorbidity screening following consultation for acute gout in primary care. Rheumatology 2010;49:105–11. 10.1093/rheumatology/kep332
    1. Bhala N, Emberson J, Merhi A, et al. . Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 2013;382:769–79. 10.1016/S0140-6736(13)60900-9
    1. Janssens HJEM, Janssen M, van de Lisdonk EH, et al. . Use of oral prednisolone or naproxen for the treatment of gout arthritis: a double-blind, randomised equivalence trial. Lancet 2008;371:1854–60. 10.1016/S0140-6736(08)60799-0
    1. Schlesinger N, Schumacher R, Catton M, et al. . Colchicine for acute gout. Cochrane Database Syst Rev 2006:CD006190 10.1002/14651858.CD006190
    1. van Echteld I, Wechalekar MD, Schlesinger N, et al. . Colchicine for acute gout. Cochrane Database Syst Rev 2014:CD006190 10.1002/14651858.CD006190.pub2
    1. Ahern MJ, Reid C, Gordon TP, et al. . Does colchicine work? the results of the first controlled study in acute gout. Aust N Z J Med 1987;17:301–4. 10.1111/j.1445-5994.1987.tb01232.x
    1. Terkeltaub RA, Furst DE, Bennett K, et al. . High versus low dosing of oral colchicine for early acute gout flare: twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study. Arthritis Rheum 2010;62:1060–8. 10.1002/art.27327
    1. Joint Formulary Committee British National formulary. 75th ed London: BMJ Group and Pharmaceutical Press, 2018.
    1. Dworkin RH, Turk DC, Farrar JT, et al. . Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain 2005;113:9–19. 10.1016/j.pain.2004.09.012
    1. Herdman M, Gudex C, Lloyd A, et al. . Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res 2011;20:1727–36. 10.1007/s11136-011-9903-x
    1. Cohen J. Statistical power analysis for the behavioral sciences. 2nd edn Hillsdale: NJ, Lawrence Earlbaum Associates, 1988.
    1. Diggle P, Heagerty LK, et al. . Analysis of longitudinal analysis. 2nd edn Oxford: Oxford University Press, 2002.
    1. Hardt J, Herke M, Leonhart R. Auxiliary variables in multiple imputation in regression with missing X: a warning against including too many in small sample research. BMC Med Res Methodol 2012;12:184 10.1186/1471-2288-12-184
    1. White IR, Royston P, Wood AM. Multiple imputation using chained equations: issues and guidance for practice. Stat Med 2011;30:377–99. 10.1002/sim.4067
    1. Altman DG. Confidence intervals for the number needed to treat. BMJ 1998;317:1309–12. 10.1136/bmj.317.7168.1309
    1. Devlin NJ, Shah KK, Feng Y, et al. . Valuing health-related quality of life: an EQ-5D-5L value set for England. Health Econ 2018;27:7–22. 10.1002/hec.3564
    1. Briggs AH, Gray AM. Handling uncertainty in economic evaluations of healthcare interventions. BMJ 1999;319:635–8. 10.1136/bmj.319.7210.635
    1. van Hout BA, Al MJ, Gordon GS, et al. . Costs, effects and C/E-ratios alongside a clinical trial. Health Econ 1994;3:309–19. 10.1002/hec.4730030505
    1. Standard occupational classification (SOC), 2000. Available:
    1. Farrar JT, Young JP, LaMoreaux L, et al. . Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 2001;94:149–58. 10.1016/S0304-3959(01)00349-9
    1. Meier CR, Jick H. Omeprazole, other antiulcer drugs and newly diagnosed gout. Br J Clin Pharmacol 1997;44:175–8. 10.1046/j.1365-2125.1997.00647.x
    1. Janssens HJEM, Fransen J, van de Lisdonk EH, et al. . A diagnostic rule for acute gouty arthritis in primary care without joint fluid analysis. Arch Intern Med 2010;170:1120–6. 10.1001/archinternmed.2010.196
    1. Accord Healthcare Ltd Summary of product characteristics. naproxen 250mg tablets. Available: [Accessed 13 Feb 2017].
    1. Qaseem A, Harris RP, Forciea MA, et al. . Management of acute and recurrent gout: a clinical practice guideline from the American College of physicians. Ann Intern Med 2017;166:58–68. 10.7326/M16-0570

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