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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02578394
Recruitment Status : Unknown
Verified April 2016 by Southend University Hospital Foundation NHS Trust.
Recruitment status was:  Recruiting
First Posted : October 19, 2015
Last Update Posted : April 11, 2016
Sponsor:
Collaborators:
Anglia Ruskin University
University of East Anglia
University of Essex
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
Southend University Hospital Foundation NHS Trust

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.

Condition or disease Intervention/treatment Phase
Gout Chronic Kidney Diseases Drug: Anakinra 100mg and Placebo Depo-Medrone Drug: Depo-Medrone 120mg and Placebo (Anakinra) Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : April 2016
Estimated Primary Completion Date : June 2017
Estimated Study Completion Date : August 2017


Arm Intervention/treatment
Active Comparator: Group A
Anakinra 100mg and Placebo Depo-Medrone
Drug: 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%.
Other Name: Kineret

Active Comparator: Group B
Depo-Medrone 120mg and Placebo (Anakinra)
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.
Other Name: Methylprednisolone Acetate




Primary Outcome Measures :
  1. Resolution of pain: time to 50% reduction and complete resolution of pain in self-assessed pain intensity in the joint most affected. [ Time Frame: Baseline (Day 1) to Day 7 ]
    VAS (0-100mm) and 5-point Likert scale.


Secondary Outcome Measures :
  1. Participant reported outcome measure of treatment response [ Time Frame: Day 2, Day 3, Day 4, Day 5, Day 6 and Day 7 ]
    5-point Likert scale score

  2. Physician / Investigator assessment of joint tenderness and swelling [ Time Frame: Day 1, Day 2, Day 4 and Day 7 ]
    4-point Likert scale score

  3. Participant assessment of activity limitation [ Time Frame: Day 1, Day 2, Day 5, Day 7 ]
    Lower Extremity Functional Scale score

  4. Participant assessment of activity limitation and quality of life [ Time Frame: Day 1, Day 2, Day 4, Day 7 and 8 weeks ]
    EQ-5D-5L health states will be used to calculate the index. Health profiles will be obtained and Quality Adjusted Life Years will be derived

  5. Participant assessment of activity limitation and quality of life using HAQ-DI [ Time Frame: Day 1, Day 7 and 8 ]
    Scores calculated from single scales and each dimension

  6. Participant assessment of quality of life [ Time Frame: Day 1, Day 7 and 8 ]
    SF-36 score

  7. Healthcare resource use [ Time Frame: 8 weeks ]
    Highly modified client service use inventory score

  8. CRP [ Time Frame: Day 1, Day 4 and Day 7 ]
    Changes in CRP

  9. White Cell Count [ Time Frame: Day 1, Day 4 and Day 7 ]
    Changes in white cell count. Number of participants who develop neutropenia

  10. eGFR [ Time Frame: Day 1, Day 4 and Day 7 ]
    Changes in eGFR

  11. Safety reporting [ Time Frame: Day 1 to 8 weeks ]
    Number of participants with treatment-related adverse events as assessed by CTCAE v4.0



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02578394


Contacts
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Contact: Gowrie Balasubramaniam, MB ChB 01702 385856 g.balasubramaniam@southend.nhs.uk
Contact: Bhaskar Dasgupta, MB BS 01702 385856 bhaskar.dasgupta@southend.nhs.uk

Locations
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United Kingdom
Southend University Hospital NHS Foundation Trust Recruiting
Southend on Sea, Essex, United Kingdom, SS0 0RY
Contact: Gowrie Balasubramaniam    01702435555 ext 8430    G.Balasubramaniam@southend.nhs.uk   
Contact: Craig Mackerness    01702 385089    craig.mackerness@southend.nhs.uk   
Sponsors and Collaborators
Southend University Hospital Foundation NHS Trust
Anglia Ruskin University
University of East Anglia
University of Essex
National Institute for Health Research, United Kingdom
Investigators
Layout table for investigator information
Principal Investigator: Gowrie Balasubramaniam, MB ChB Southend University Hospital

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Southend University Hospital Foundation NHS Trust
ClinicalTrials.gov Identifier: NCT02578394    
Other Study ID Numbers: P0850
2015-001787-19 ( EudraCT Number )
PB-PG-0614-34090 ( Other Grant/Funding Number: National Institute of Health Research )
First Posted: October 19, 2015    Key Record Dates
Last Update Posted: April 11, 2016
Last Verified: April 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Southend University Hospital Foundation NHS Trust:
Gout
Kidney
Depo-Medrone
Anakinra
Additional relevant MeSH terms:
Layout table for MeSH terms
Gout
Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Renal Insufficiency
Arthritis
Joint Diseases
Musculoskeletal Diseases
Crystal Arthropathies
Rheumatic Diseases
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Interleukin 1 Receptor Antagonist Protein
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones