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

Assistance Publique - Hôpitaux de Paris204 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 3b/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)

Outcomes

Primary Outcomes

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

Time frame: Day 3

Secondary Outcomes

Percentage of responders (improvement ≥ 50%) at day 5

Time frame: Day 5

Percentage of flare resolution (improvement ≥ 80%) at day 5

Time frame: Day 5

Time to treatment response

Time frame: Day 3 or Day 5

Time to flare resolution

Time frame: Day 3 or Day 5

Treatment duration

Time frame: Day3 or Day 5

Duration of hospitalization

Time frame: 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

Time frame: Month 1

Healthcare consumption at month 1: total hospital stay

Healthcare consumption at month 1 assessed by total hospital stay

Time frame: Month 1

Healthcare consumption at month 1

Healthcare consumption at month 1 assessed by number and cumulative duration of sick leave related to gout

Time frame: Month 1

Side effects

Time frame: Month 1

Comorbidity decompensations at month 1 : DT2 decompensation

Comorbidity decompensations at month 1 assessed by DT2 decompensation measure

Time frame: Month 1

Comorbidity decompensations at month 1: Blood pressure

Comorbidity decompensations at month 1 assessed by Blood pressure measure

Time frame: Month 1

Comorbidity decompensations at month 1: Hypertension

Comorbidity decompensations at month 1 assessed by hypertension measure

Time frame: Month 1

Comorbidity decompensations at month 1: Weight

Comorbidity decompensations at month 1 assessed by Weight measure

Time frame: 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

Time frame: Month 1

Comorbidity decompensations at month 1: Blood analysis of serum creatinine level

Comorbidity decompensations at month 1 assessed by serum creatinine level measure

Time frame: Month 1

Comorbidity decompensations at month 1: Blood analysis of epidermal Growth Factor Receptor (eGFR)

Comorbidity decompensations at month 1 assessed by eGFR measure

Time frame: Month 1

Comorbidity decompensations at month 1: Blood analysis of C reactive protein (CRP)

Comorbidity decompensations at month 1 assessed by CRP measure

Time frame: Month 1

Comorbidity decompensations at month 1: Blood analysis of HbA1C

Comorbidity decompensations at month 1 assessed by HbA1C measure

Time frame: Month 1

Comorbidity decompensations at month 1: Blood analysis of total cholesterol

Comorbidity decompensations at month 1 assessed by total cholesterol measure

Time frame: Month 1

Comorbidity decompensations at month 1: Blood analysis of LDL cholesterol

Comorbidity decompensations at month 1 assessed by HDL cholesterol measure

Time frame: Month 1

Comorbidity decompensations at month 1: Blood analysis of HDL cholesterol

Comorbidity decompensations at month 1 assessed by HDL cholesterol measure

Time frame: Month 1

Comorbidity decompensations at month 1: Blood analysis of triglyceride

Comorbidity decompensations at month 1 assessed by triglyceride measure

Time frame: Month 1

Comorbidity decompensations at month 1: Blood analysis of glycaemia

Comorbidity decompensations at month 1 assessed by glycaemia measure

Time frame: 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

Time frame: 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

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: Dat 3 or day 5

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes