Anakinra vs Prednisone to Treat Gout Flare in Patients With Chronic Kidney Disease Stage 4/5 or Renal Transplantation

Study Overview
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Brief Summary
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Gout is secondary to urate crystal deposition after chronic elevation of serum urate level. Urate crystal deposition is responsible for acute and recurrent inflammatory flares which can be treated with colchicine, non-steroid anti-inflammatory drugs (NSAID), corticosteroid or interleukin (IL)-1b blockade. Colchicine and NSAID are contra-indicated in patients with chronic renal disease (CKD) stage 4/5 or with renal transplantation. In these patients gout flare is treated with high dose of corticosteroid or IL-1b inhibitors. Frequent use of high dose of corticosteroid can worsen gout comorbidities including mellitus diabetes type 2, hypertension, obesity and dyslipidemia. Anakinra, an IL-1b receptor antagonist, is efficient in gout flare in patients without CKD stage 4/5. The aim of this study is to demonstrate that anakinra is superior to prednisone to treat gout flare in patients with CKD 4/5 or renal transplantation.

Detailed Description
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The study will include 234 gouty patients with CKD 4/5 or renal transplantation with gout flare This study will include the following visits: - Selection/inclusion visit (V0): Patient with gout flare and CKD 4/5 or renal transplantation will be included and randomized to receive either anakinra 100 mg/d or prednisone 30 mg/d. -Visit from day (d)0 to d5: included patients will be hospitalized and treatment will be administrated by a nurse. Treatment will be stopped if patient had ≥ 80% improvement. Treatment response is defined by improvement ≥ 50%. Patient will be evaluated every day from d0 to d5. At d3, if improvement is < 50%, patient will be considered as non-responder and patient will be managed as physician's habits. At d5, if improvement is < 80%, patient will be managed as physician's habits Between d1 and d5, if improvement ≥ 80%, patient can be discharged and will have a visit at d5 as outpatient. - Visit month (M)1 end of research: clinical evaluation of gout, demographic characteristics, medication, number of gout flare within the month, number of hospitalization and/or medical consultation within the month, blood analysis (serum creatinine level, eGFR, SUL, CRP, HbA1C, total, HDL and LDL cholesterol, triglyceride, glycaemia). The study ends after the M1 consultation. The total duration of participation in the study is 1 month.

Official Title
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Anakinra vs Prednisone to Treat Gout Flare in Patients With Chronic Kidney Disease Stage 4/5 or Renal Transplantation: a Randomized, Double Blinded, Multicenter Study

Conditions
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Gout, Chronic Kidney Disease, Renal Transplantation

Intervention / Treatment
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* Drug: Anakinra 100Mg/0.67Ml Inj Syringe
* Drug: Prednisone
* Drug: Placebo of Prednisone
* Drug: Placebo of Anakinra


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged over 18 years old Gout confirmed by identification of urate crystals by joint fluid or tophus analysis or by ultrasound of the affected joint and/or Gout according to Nijmegen criteria (presence of a score ≥ 8/13) depending on the following items: Man (2 pts) Previous crisis (2 pts) Involvement of first metatarsophalangeal joint (MTP1) (2.5 pts) Maximum pain within 24 hours (0.5pt) Redness (1 pt) HTA or cardiovascular disease (1.5 pts) SUL > 360 μmol/l during the crisis (3.5 pts) Chronic kidney disease stage 4/5 or renal transplantation Flare ≤ 5 days Pain assessed by visual analogical scale > 4/10 Exclusion Criteria: Participating in another trial including the administration of a drug Active infection History of anakinra or prednisone allergy Contra-indication of anakinra or prednisone Neutrophil count < 1000/mm3 (not due to ethnic cause) Difficulty understanding French Illiteracy Pregnant women or breastfeeding mothers (see PHC article L.1121-5) Persons deprived of liberty by judicial or administrative decision, persons receiving psychiatric care under Sections L. 3212-1 and L. 3213-1 and persons admitted to a health or social institution for purposes other than research (see CSP Article L.1121-6) Major persons subject to a measure of legal protection or unseeding to express consent (see PHC Article L.1121-8) Persons not affiliated to a social security plan or beneficiaries of such a plan (see PHC Article L.1121-8-1)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anakinra<br>Anakinra 100 mg/d+Placebo of Prednisone | Drug: Anakinra 100Mg/0.67Ml Inj Syringe<br>* Anakinra 100 mg/d subcutaneous injection<br>Drug: Placebo of Prednisone<br>* Placebo of Prednisone<br>|
| Active Comparator: Prednisone<br>Prednisone 30 mg/d+Placebo of Anakinra | Drug: Prednisone<br>* Prednisone 30 mg/d<br>Drug: Placebo of Anakinra<br>* Placebo of Anakinra<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain difference between Day 3 and treatment initiation | Pain difference between day 3 and treatment initiation assessed by visual analogical scale (VAS) from 0 to 10 VAS = 0, no pain VAS =10, maximal pain | Day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of responders (improvement ≥ 50%) at day 5 | Percentage of responders (improvement ≥ 50%) at day 5 | Day 5 | 
| Percentage of flare resolution (improvement ≥ 80%) at day 5 | Percentage of flare resolution (improvement ≥ 80%) at day 5 | Day 5 | 
| Time to treatment response | Time to treatment response | Day 3 or Day 5 | 
| Time to flare resolution | Time to flare resolution | Day 3 or Day 5 | 
| Treatment duration | Treatment duration | Day3 or Day 5 | 
| Duration of hospitalization | Duration of hospitalization | Day 3 or Day 5 | 
| Healthcare consumption at month 1 : number of consultations and hospitalizations related to gout flare | Healthcare consumption at month 1 assessed by number of consultations and hospitalizations related to gout flare | Month 1 | 
| Healthcare consumption at month 1: total hospital stay | Healthcare consumption at month 1 assessed by total hospital stay | Month 1 | 
| Healthcare consumption at month 1 | Healthcare consumption at month 1 assessed by number and cumulative duration of sick leave related to gout | Month 1 | 
| Side effects | Side effects | Month 1 | 
| Comorbidity decompensations at month 1 : DT2 decompensation | Comorbidity decompensations at month 1 assessed by DT2 decompensation measure | Month 1 | 
| Comorbidity decompensations at month 1: Blood pressure | Comorbidity decompensations at month 1 assessed by Blood pressure measure | Month 1 | 
| Comorbidity decompensations at month 1: Hypertension | Comorbidity decompensations at month 1 assessed by hypertension measure | Month 1 | 
| Comorbidity decompensations at month 1: Weight | Comorbidity decompensations at month 1 assessed by Weight measure | Month 1 | 
| Comorbidity decompensations at month 1: number of Cardiovascular events : coronary disease, heart attack, stroke | Comorbidity decompensations at month 1 assessed by number of Cardiovascular events : coronary disease, heart attack, stroke | Month 1 | 
| Comorbidity decompensations at month 1: Blood analysis of serum creatinine level | Comorbidity decompensations at month 1 assessed by serum creatinine level measure | Month 1 | 
| Comorbidity decompensations at month 1: Blood analysis of epidermal Growth Factor Receptor (eGFR) | Comorbidity decompensations at month 1 assessed by eGFR measure | Month 1 | 
| Comorbidity decompensations at month 1: Blood analysis of C reactive protein (CRP) | Comorbidity decompensations at month 1 assessed by CRP measure | Month 1 | 
| Comorbidity decompensations at month 1: Blood analysis of HbA1C | Comorbidity decompensations at month 1 assessed by HbA1C measure | Month 1 | 
| Comorbidity decompensations at month 1: Blood analysis of total cholesterol | Comorbidity decompensations at month 1 assessed by total cholesterol measure | Month 1 | 
| Comorbidity decompensations at month 1: Blood analysis of LDL cholesterol | Comorbidity decompensations at month 1 assessed by HDL cholesterol measure | Month 1 | 
| Comorbidity decompensations at month 1: Blood analysis of HDL cholesterol | Comorbidity decompensations at month 1 assessed by HDL cholesterol measure | Month 1 | 
| Comorbidity decompensations at month 1: Blood analysis of triglyceride | Comorbidity decompensations at month 1 assessed by triglyceride measure | Month 1 | 
| Comorbidity decompensations at month 1: Blood analysis of glycaemia | Comorbidity decompensations at month 1 assessed by glycaemia measure | Month 1 | 
| site injection reaction during day 0 to day 5: pain | site injection reaction during day 0 to day 5 assessed by pain (0-10 scale VAS) measure | Dat 3 or day 5 | 
| site injection reaction during day 0 to day 5: inflammatory reaction | site injection reaction during day 0 to day 5 assessed by CRP level measure | Dat 3 or day 5 | 
| site injection reaction during day 0 to day 5: swelling (yes/no) | site injection reaction during day 0 to day 5 assessed by swelling (yes/no) | Dat 3 or day 5 | 
| site injection reaction during day 0 to day 5: itching (yes/no) | site injection reaction during day 0 to day 5 assessed by itching (yes/no) | Dat 3 or day 5 | 
| site injection reaction during day 0 to day 5: redness (yes/no) | site injection reaction during day 0 to day 5 assessed by redness (yes/no) | Dat 3 or day 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gout, Flare, Urate crystals, Chronic kidney disease, Anakinra, IL-1b, Corticosteroid, Renal transplantation