Clinical trial NCT02578394: Anakinra vs. Steroids for the Treatment of Gout Attacks in Patients With Renal Disease (ASGARD): A Feasibility Study
Official title: A Feasibility Study to Undertake a Definitive Randomised Multi-centre, Double-blind, Double-dummy Controlled Study of a Novel Agent Anakinra vs. Depo-Medrone for Acute Gout Attacks in Patients With Moderate Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Gout
Chronic Kidney Diseases
Keywords: Gout
Kidney
Depo-Medrone
Anakinra
Lead sponsor: Mid and South Essex NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Anglia Ruskin University
name: University of East Anglia
name: University of Essex
name: National Institute for Health Research, United Kingdom
First posted: 2015-10-19
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: Gout is a common condition that affects 1 in 40 people in the UK. It causes painful "attacks" of joint swelling, redness and tenderness, mostly affecting the foot, ankle, knee, hand and wrist. It is common in people with kidney disease, who also tend to be older people with other medical conditions such as high blood pressure, heart disease and diabetes. The investigators do not know the safest and best way to treat gout attacks in this increasing cohort of people. A lot of people are given treatment that can worsen their kidney disease, along with their other medical conditions.

The investigators want to compare the safest treatment currently available, steroids, with a new treatment called Anakinra. This treatment stops the action of a chemical called interleukin-1 which has been discovered to play an important role in gout attacks. This treatment has already been used to treat gout attacks in a handful of patients with kidney disease. The investigators feel it may be a better alternative to steroid treatment which can sometime worsen diabetes, heart disease and blood pressure. Participants will predominantly be followed-up for one week and a final 8 week follow-up, and be recruited from hospitals in the East of England.

A definitive scientific study comparing these two treatments would involve a big expensive study requiring large numbers of patients and large amounts of information to be collected. Before the investigators do a big study like this, the investigators want to perform a small study using a smaller number of patients (32 patients) over a period of 22 months in total. It will then give us information to plan a larger study to answer the question of which treatment may be better, safer and provides the most value for money for the NHS.

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).

Primary outcomes:
measure: Resolution of pain: time to 50% reduction and complete resolution of pain in self-assessed pain intensity in the joint most affected.
timeFrame: Baseline (Day 1) to Day 7
Secondary outcomes:
measure: Participant reported outcome measure of treatment response
timeFrame: Day 2, Day 3, Day 4, Day 5, Day 6 and Day 7
measure: Physician / Investigator assessment of joint tenderness and swelling
timeFrame: Day 1, Day 2, Day 4 and Day 7
measure: Participant assessment of activity limitation
timeFrame: Day 1, Day 2, Day 5, Day 7
measure: Participant assessment of activity limitation and quality of life
timeFrame: Day 1, Day 2, Day 4, Day 7 and 8 weeks
measure: Participant assessment of activity limitation and quality of life using HAQ-DI
timeFrame: Day 1, Day 7 and 8
measure: Participant assessment of quality of life
timeFrame: Day 1, Day 7 and 8
measure: Healthcare resource use
timeFrame: 8 weeks
measure: CRP
timeFrame: Day 1, Day 4 and Day 7
measure: White Cell Count
timeFrame: Day 1, Day 4 and Day 7
measure: eGFR
timeFrame: Day 1, Day 4 and Day 7
measure: Safety reporting
timeFrame: Day 1 to 8 weeks
Other outcomes:
Locations:
city: Southend on Sea
country: United Kingdom
facility: Southend Hospital
state: Essex
Study officials:
affiliation: Mid and South Essex NHS Foundation Trust
name: Gowrie Balasubramaniam, MB ChB
role: PRINCIPAL_INVESTIGATOR
References:
citation: Balasubramaniam G, Parker T, Turner D, Parker M, Scales J, Harnett P, Harrison M, Ahmed K, Bhagat S, Marianayagam T, Pitzalis C, Mallen C, Roddy E, Almond M, Dasgupta B. Feasibility randomised multicentre, double-blind, double-dummy controlled trial of anakinra, an interleukin-1 receptor antagonist versus intramuscular methylprednisolone for acute gout attacks in patients with chronic kidney disease (ASGARD): protocol study. BMJ Open. 2017 Sep 5;7(9):e017121. doi: 10.1136/bmjopen-2017-017121.