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

NCT ID: NCT02578394

Last Updated: 2022-04-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-30
• Study Completion Date: 2022-01-26

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.

Conditions

Gout; Chronic Kidney Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Group A

Anakinra 100mg and Placebo Depo-Medrone

Group Type: ACTIVE_COMPARATOR

Anakinra 100mg and Placebo Depo-Medrone

Intervention Type: DRUG

Anakinra 100mg injection S/C Day 1 to Day 5 and Placebo Depo-Medrone (Lipofundin 3mL) I/M Day 1. Anakinra is an interleukin-1 receptor antagonist. Placebo for Depo-Medrone placebo is Lipofundin MCT/LCT 10%.

Group B

Depo-Medrone 120mg and Placebo (Anakinra)

Group Type: ACTIVE_COMPARATOR

Depo-Medrone 120mg and Placebo (Anakinra)

Intervention Type: DRUG

Depo-Medrone 120mg in 3mL. Placebo for Anakinra supplied from manufacturer. 120mg Depo-Medrone I/M Day 1 and Placebo Anakinra 100mg injection S/C Day 1 to Day 5.

Interventions

Anakinra 100mg and Placebo Depo-Medrone

Anakinra 100mg injection S/C Day 1 to Day 5 and Placebo Depo-Medrone (Lipofundin 3mL) I/M Day 1. Anakinra is an interleukin-1 receptor antagonist. Placebo for Depo-Medrone placebo is Lipofundin MCT/LCT 10%.

Intervention Type: DRUG

Depo-Medrone 120mg and Placebo (Anakinra)

Depo-Medrone 120mg in 3mL. Placebo for Anakinra supplied from manufacturer. 120mg Depo-Medrone I/M Day 1 and Placebo Anakinra 100mg injection S/C Day 1 to Day 5.

Intervention Type: DRUG

Other Intervention Names

Kineret; Methylprednisolone Acetate

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Anglia Ruskin University

OTHER

Sponsor Role: collaborator

University of East Anglia

OTHER

Sponsor Role: collaborator

University of Essex

OTHER

Sponsor Role: collaborator

National Institute for Health Research, United Kingdom

OTHER_GOV

Sponsor Role: collaborator

Mid and South Essex NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gowrie Balasubramaniam, MB ChB

Role: PRINCIPAL_INVESTIGATOR

Mid and South Essex NHS Foundation Trust

Locations

Southend Hospital

Southend-on-Sea, Essex, United Kingdom

Countries

United Kingdom

References

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.

Reference Type: DERIVED

PMID: 28877949 (View on PubMed)

Other Identifiers

2015-001787-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PB-PG-0614-34090

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

P0850

Identifier Type: -

Identifier Source: org_study_id