Anakinra versus intramuscular methylprednisolone acetate for gout flares in people with chronic kidney disease (ASGARD): a UK randomised multicentre, double-blind, double-dummy controlled feasibility study with economic, qualitative and safety assess
Gowrie Balasubramaniam, Mike Almond, Patrick Harnett, David Turner, Jonathan Scales, Jufen Zhang, Carmel Moore, Karen Hayden, Edward Roddy, Christian Mallen, John Stack, Shweta Bhagat, Nora Ng, Andrew Rutherford, Bhaskar DasguptaObjectives
Anakinra versus steroids for gout flares in people with renal disease (ASGARD) is a feasibility trial of undertaking a double-blind, double dummy randomised controlled trial of Anakinra versus intramuscular methylprednisolone acetate in people with gout and chronic kidney disease.
Design
A two-arm parallel group, double-blind, double-dummy, multicentre, randomised controlled trial.
Setting
ASGARD was undertaken in four centres in secondary care.
Intervention
Subcutaneous anakinra 100 mg daily for 5 days versus intramuscular methylprednisolone acetate 120 mg for gout flares in people with chronic kidney disease (estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 ).
Primary and secondary outcome measures
Primary outcome measures were feasibility criteria of recruitment (32 participants over 15 months), enrolment of >70% of eligible participants, <10% treatment crossover or failure and completion of 5 out of 7 participant-reported pain assessments by 85% of participants. Secondary outcome measures included time to 50% reduction and complete resolution of pain (self-assessment) on Visual Analogue Scale (0–100 mm) and 5-point Likert scale (D1 to D7), physician assessment of joint tenderness and swelling (D1, D2 and D7), patient-reported outcome measure (D1 to D7), patient assessment of activity limitation and quality of life: Health Assessment Questionnaire Disability Index and 36-Item Short Form Survey (D1, D7 and 8 weeks); EuroQol 5-Dimension 5-Level at D1, D2, D7 and 8 weeks; Lower Extremity Functional Scale at D1, D2, D7. Safety data, health economic data and qualitative analysis of participant experience were also collected.
Results
The feasibility trial did not meet its overall criteria for success due to under-recruitment. It met procedural feasibility of recruiting ≥70% of eligible patients and ≤10% treatment crossovers or failure, 85% of participants completing 5 out of 7 participant-reported pain assessments (excluding four participants who did not receive allocated treatment). 21 participants (mean age 72 years, mean eGFR 44 mL/min/1.73 m 2 ) were randomised; 17 received per protocol treatment. Mean reduction in pain after 7 days was 46.8 from baseline by 100 mm visual analogue score. Anakinra appeared to have a shorter time to pain reduction; however, this must be confirmed in a larger trial. Functional and quality of life assessments were highly completed. Health resource use was higher when assessed by health records. Qualitative feedback from participants alluded to high questionnaire burden and delays in receiving treatment.
Conclusions
We demonstrated the feasibility of conducting a definitive randomised controlled trial with insights from treatment effects, safety data, reconciliation of assessments, economic evaluation and participant experience. Improved case finding in the community, with streamlined processes during gout flare should be explored before recommendation for future trial can be made.
Trial registration numbers
EudraCT No. 2015-001787-19. NCT/ClinicalTrials.gov No.