Anakinra vs Prednisone to Treat Gout Flare in Patients With Chronic Kidney Disease Stage 4/5 or Renal Transplantation
- Conditions
- Chronic Kidney DiseaseRenal TransplantationGout
- Interventions
- Drug: Placebo of AnakinraDrug: Placebo of Prednisone
- Registration Number
- NCT04844814
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- SUSPENDED
- Sex
- All
- Target Recruitment
- 204
- 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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Anakinra Anakinra 100Mg/0.67Ml Inj Syringe Anakinra 100 mg/d+Placebo of Prednisone Prednisone Placebo of Anakinra Prednisone 30 mg/d+Placebo of Anakinra Anakinra Placebo of Prednisone Anakinra 100 mg/d+Placebo of Prednisone Prednisone Prednisone Prednisone 30 mg/d+Placebo of Anakinra
- Primary Outcome Measures
Name Time Method Pain difference between Day 3 and treatment initiation Day 3 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
- Secondary Outcome Measures
Name Time Method Treatment duration Day3 or Day 5 Treatment duration
Comorbidity decompensations at month 1: Hypertension Month 1 Comorbidity decompensations at month 1 assessed by hypertension measure
Comorbidity decompensations at month 1: Blood analysis of C reactive protein (CRP) Month 1 Comorbidity decompensations at month 1 assessed by CRP measure
Duration of hospitalization Day 3 or Day 5 Duration of hospitalization
Healthcare consumption at month 1 : number of consultations and hospitalizations related to gout flare Month 1 Healthcare consumption at month 1 assessed by number of consultations and hospitalizations related to gout flare
Healthcare consumption at month 1: total hospital stay Month 1 Healthcare consumption at month 1 assessed by total hospital stay
Percentage of responders (improvement ≥ 50%) at day 5 Day 5 Percentage of responders (improvement ≥ 50%) at day 5
Time to treatment response Day 3 or Day 5 Time to treatment response
Healthcare consumption at month 1 Month 1 Healthcare consumption at month 1 assessed by number and cumulative duration of sick leave related to gout
Comorbidity decompensations at month 1 : DT2 decompensation Month 1 Comorbidity decompensations at month 1 assessed by DT2 decompensation measure
Percentage of flare resolution (improvement ≥ 80%) at day 5 Day 5 Percentage of flare resolution (improvement ≥ 80%) at day 5
Side effects Month 1 Side effects
Comorbidity decompensations at month 1: Blood pressure Month 1 Comorbidity decompensations at month 1 assessed by Blood pressure measure
Time to flare resolution Day 3 or Day 5 Time to flare resolution
Comorbidity decompensations at month 1: Weight Month 1 Comorbidity decompensations at month 1 assessed by Weight measure
Comorbidity decompensations at month 1: number of Cardiovascular events : coronary disease, heart attack, stroke Month 1 Comorbidity decompensations at month 1 assessed by number of Cardiovascular events : coronary disease, heart attack, stroke
Comorbidity decompensations at month 1: Blood analysis of serum creatinine level Month 1 Comorbidity decompensations at month 1 assessed by serum creatinine level measure
Comorbidity decompensations at month 1: Blood analysis of epidermal Growth Factor Receptor (eGFR) Month 1 Comorbidity decompensations at month 1 assessed by eGFR measure
Comorbidity decompensations at month 1: Blood analysis of HbA1C Month 1 Comorbidity decompensations at month 1 assessed by HbA1C measure
Comorbidity decompensations at month 1: Blood analysis of total cholesterol Month 1 Comorbidity decompensations at month 1 assessed by total cholesterol measure
Comorbidity decompensations at month 1: Blood analysis of HDL cholesterol Month 1 Comorbidity decompensations at month 1 assessed by HDL cholesterol measure
Comorbidity decompensations at month 1: Blood analysis of triglyceride Month 1 Comorbidity decompensations at month 1 assessed by triglyceride measure
Comorbidity decompensations at month 1: Blood analysis of glycaemia Month 1 Comorbidity decompensations at month 1 assessed by glycaemia measure
site injection reaction during day 0 to day 5: pain Dat 3 or day 5 site injection reaction during day 0 to day 5 assessed by pain (0-10 scale VAS) measure
Comorbidity decompensations at month 1: Blood analysis of LDL cholesterol Month 1 Comorbidity decompensations at month 1 assessed by HDL cholesterol measure
site injection reaction during day 0 to day 5: itching (yes/no) Dat 3 or day 5 site injection reaction during day 0 to day 5 assessed by itching (yes/no)
site injection reaction during day 0 to day 5: inflammatory reaction Dat 3 or day 5 site injection reaction during day 0 to day 5 assessed by CRP level measure
site injection reaction during day 0 to day 5: redness (yes/no) Dat 3 or day 5 site injection reaction during day 0 to day 5 assessed by redness (yes/no)
site injection reaction during day 0 to day 5: swelling (yes/no) Dat 3 or day 5 site injection reaction during day 0 to day 5 assessed by swelling (yes/no)
Trial Locations
- Locations (1)
Rhumathology department
🇫🇷Paris, Ile-De-France, France