Clinical trial: Anakinra vs. Steroids for the Treatment of Gout Attacks in Patients With Renal Disease (ASGARD): A Feasibility Study (NCT02578394)

Eligibility criteria:
Inclusion Criteria:

          1. Subjects capable of giving informed consent.

          2. Male or non-pregnant, non-nursing female

          3. ≥ 18 years of age

          4. eGFR < 60mls/min/1.73m2 and ≥ 30mls/min/1.73m2 as calculated using serum creatinine
             and modified MDRD formula as per renal association guidelines.

          5. Diagnosis of gout arthritis as defined by the American College of Rheumatology 1977
             preliminary criteria (this criteria is currently endorsed by NICE guidelines).

          6. Gout flare less ≤ 36 hours

          7. Baseline pain intensity > or equal to 50mm on the 0-100 mm VAS. In the case of
             multiple joints (≤ 3), the most affected joint will be assessed.

        Exclusion Criteria:

          1. Treatment with NSAIDS in last 48 hours, systemic steroids in last 4 weeks or
             colchicine within 7 days.

          2. Polyarticular gout, i.e. affecting four or more 4 joints

          3. Rheumatoid arthritis, evidence/suspicion of infectious/septic arthritis, or other
             acute inflammatory arthritis such as systemic lupus erythematosus, mixed connective
             tissue disease, scleroderma, polymyositis, or significant systemic involvement
             secondary to rheumatoid arthritis.

          4. Con-current immunosuppression/immunomodulatory treatment (Calcineurin inhibitor,
             anti-proliferative or biologic) therapy for other reason i.e. organ transplant.

          5. Prior history or current inflammatory joint disease other than gout (e.g. rheumatoid
             arthritis (RA), reactive arthritis, psoriatic arthritis, seronegative
             spondyloarthropathy, Lyme disease). Concurrent medication for RA like methotrexate and
             anti-TNF treatment has been associated with increased risk of neutropenia and
             infection.

          6. Current active malignancy (with the exception of basal cell or squamous cell carcinoma
             of the skin, cervical intraepithelial neoplasia and non-metastatic/advanced prostate
             cancer).

          7. Any patients with contra-indication to intramuscular injection such as coagulopathy or
             thrombocytopenia (Platelet count<100 x 109/L (100,000/mm3)).

          8. Abnormal liver function tests: Total bilirubin>upper limit of normal, Alanine
             aminotransferase (ALT) or Aspartate Aminotransferase (AST) >2 times upper limit of
             normal.

          9. Haemoglobin <85g/L (8.5 g/dL)

         10. White blood cell (WBC) count<1.5 x 109/L (1000/mm3), absolute neutrophil count<1.5 x
             109/L (1000/mm3)

         11. Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary
             (including obstructive pulmonary disease), hepatic, endocrine (including uncontrolled
             diabetes) or gastrointestinal disease.

         12. Known positive hepatitis B virus surface antigen (HBsAg), hepatitis C (HCV) antibody
             or HIV.

         13. Females of child bearing potential who are not willing to use highly effective birth
             control methods from the time of consent to one week after treatment discontinuation.
             Highly effective method of contraception (hormonal or barrier method of birth control;
             abstinence) consist of:

               -  Combined (estrogen and progestogen containing) hormonal contraception associated
                  with inhibition of ovulation; oral, intravaginal, transdermal.

               -  Progestogen-only hormonal contraception associated with inhibition of ovulation;
                  oral, injectable, implantable.

               -  Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)

               -  Bilateral tubal occlusion or vasectomised partner

               -  Sexual abstinence

         14. Females of childbearing potential must have a negative pregnancy test (highly
             sensitive urine or serum pregnancy test after a confirmed menstrual period) within 7
             days prior to treatment initiation. Subjects are considered not of child bearing
             potential if they are surgically sterile (i.e. they have undergone a hysterectomy,
             bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.

         15. Females must not be breastfeeding.

         16. Patients who have had treatment as part of this trial cannot have repeat treatment for
             another flare as part of the trial.

         17. Patient with allergies to excipients of IMPs: citric acid, anhydrous, sodium chloride,
             disodium edetate dehydrate, polysorbate 80, sodium hydroxide. Hypersensitivity to E.
             Coli derived proteins, egg proteins and soy proteins. Patients with a latex allergy
             are also not eligible as the inner needle cover of the pre-filled syringe contains dry
             natural rubber (a derivative of latex).
No condition on gender to be admitted to the trial.
Accepts Healthy Volunteers
Subject must be at least 18 Years old.


Patient description (medical language): A 39-year-old man comes to the emergency department with an acute onset of severe left toe pain.  The toe is red and exhibits swelling. The patient is not febrile, and does not remember any recent trauma. Medical history is not significant except for the similar attacks and the diagnosis of gouty arthritis. His medication history includes Allopurinol to prevent gouty attacks. His father has the same medical condition. However, his older brother who is 41 years old is healthy with no history of gouty arthritis. Physical examination shows a swollen, tender first metatarsophalangeal joint.  Aspiration of the joint showed high leukocyte count, negative Gram stain, and numerous needle-shaped crystals, which is compatible with gouty arthritis.

Patient description (patient's own words): I'm a 39-year-old man and got admitted to the ER after an unbearable pain in my left toe. My toe was red and terribly swollen. I was still standing on my feet, not febrile and I don't remember hitting my head or anything. I don't have any special medical history, but I had been diagnosed with gout before. I take Lopurin to prevent my gouty attacks. My dad had the same problem, but my 41-year-old brother is healthy and does not have gouty attacks. The doctor did a physical exam and found that the joints between my toes and the rest of my foot were swollen and tender. The doctor renewed his diagnosis of gouty arthritis.

Does the patient match the trial criteria? Contradiction