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

• Status: Active, not recruiting
• Trial end date: 2021-09-01
• Target enrollment: 0
• Participant gender: All

Summary

The aim of this study is to determine the feasibility of running a phase III double-blind, double-dummy randomised controlled trial comparing Depo-Medrone 120mg intramuscular injection vs. Anakinra 100mg subcutaneous injection for 5 days for the treatment of acute gout attacks in patients with chronic kidney disease as defined by a eGFR < 60mls/min/1.73m2 and ≥ 30mls/min/1.73m2.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Mid and South Essex NHS Foundation Trust; Southend University Hospital Foundation NHS Trust
• Collaborators: Anglia Ruskin University; National Institute for Health Research, United Kingdom; University of East Anglia; University of Essex
• Treatments: Interleukin 1 Receptor Antagonist Protein; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate

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).