Clinical trial NCT04844814: Anakinra vs Prednisone to Treat Gout Flare in Patients With Chronic Kidney Disease Stage 4/5 or Renal Transplantation
Official title: 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
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
Conditions: Gout
Chronic Kidney Disease
Renal Transplantation
Keywords: Gout
Flare
Urate crystals
Chronic kidney disease
Anakinra
IL-1b
Corticosteroid
Renal transplantation
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2021-04-14
Enrollment: 204
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Pain difference between Day 3 and treatment initiation
timeFrame: Day 3
Secondary outcomes:
measure: Percentage of responders (improvement ≥ 50%) at day 5
timeFrame: Day 5
measure: Percentage of flare resolution (improvement ≥ 80%) at day 5
timeFrame: Day 5
measure: Time to treatment response
timeFrame: Day 3 or Day 5
measure: Time to flare resolution
timeFrame: Day 3 or Day 5
measure: Treatment duration
timeFrame: Day3 or Day 5
measure: Duration of hospitalization
timeFrame: Day 3 or Day 5
measure: Healthcare consumption at month 1 : number of consultations and hospitalizations related to gout flare
timeFrame: Month 1
measure: Healthcare consumption at month 1: total hospital stay
timeFrame: Month 1
measure: Healthcare consumption at month 1
timeFrame: Month 1
measure: Side effects
timeFrame: Month 1
measure: Comorbidity decompensations at month 1 : DT2 decompensation
timeFrame: Month 1
measure: Comorbidity decompensations at month 1: Blood pressure
timeFrame: Month 1
measure: Comorbidity decompensations at month 1: Hypertension
timeFrame: Month 1
measure: Comorbidity decompensations at month 1: Weight
timeFrame: Month 1
measure: Comorbidity decompensations at month 1: number of Cardiovascular events : coronary disease, heart attack, stroke
timeFrame: Month 1
measure: Comorbidity decompensations at month 1: Blood analysis of serum creatinine level
timeFrame: Month 1
measure: Comorbidity decompensations at month 1: Blood analysis of epidermal Growth Factor Receptor (eGFR)
timeFrame: Month 1
measure: Comorbidity decompensations at month 1: Blood analysis of C reactive protein (CRP)
timeFrame: Month 1
measure: Comorbidity decompensations at month 1: Blood analysis of HbA1C
timeFrame: Month 1
measure: Comorbidity decompensations at month 1: Blood analysis of total cholesterol
timeFrame: Month 1
measure: Comorbidity decompensations at month 1: Blood analysis of LDL cholesterol
timeFrame: Month 1
measure: Comorbidity decompensations at month 1: Blood analysis of HDL cholesterol
timeFrame: Month 1
measure: Comorbidity decompensations at month 1: Blood analysis of triglyceride
timeFrame: Month 1
measure: Comorbidity decompensations at month 1: Blood analysis of glycaemia
timeFrame: Month 1
measure: site injection reaction during day 0 to day 5: pain
timeFrame: Dat 3 or day 5
measure: site injection reaction during day 0 to day 5: inflammatory reaction
timeFrame: Dat 3 or day 5
measure: site injection reaction during day 0 to day 5: swelling (yes/no)
timeFrame: Dat 3 or day 5
measure: site injection reaction during day 0 to day 5: itching (yes/no)
timeFrame: Dat 3 or day 5
measure: site injection reaction during day 0 to day 5: redness (yes/no)
timeFrame: Dat 3 or day 5
Other outcomes:
Locations:
city: Paris
country: France
facility: Rhumathology department
state: Ile-De-France
Study officials:
affiliation: Hôpital Lariboisière
name: Hang-Korng EA, PhD-MD
role: PRINCIPAL_INVESTIGATOR
References: