Anakinra vs Prednisone to Treat Gout Flare in Patients With Chronic Kidney Disease Stage 4/5 or Renal Transplantation (Ana4CKD)

Assistance Publique - Hôpitaux de Paris

Status and phase: Suspended; Phase 2

Conditions: Chronic Kidney Disease; Renal Transplantation; Gout

Treatments: Drug: Placebo of Prednisone; Drug: Prednisone; Drug: Anakinra 100Mg/0.67Ml Inj Syringe; Drug: Placebo of Anakinra

Study type: Interventional

Funder types: Other

Identifiers

NCT04844814

APHP180560

Details and patient eligibility

About

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.

Full 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.

Enrollment: 204 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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204 participants in 2 patient groups

Anakinra

Experimental group

Description:

Anakinra 100 mg/d+Placebo of Prednisone

Treatment:

Drug: Anakinra 100Mg/0.67Ml Inj Syringe

Drug: Placebo of Prednisone

Prednisone

Active Comparator group

Description:

Prednisone 30 mg/d+Placebo of Anakinra

Treatment:

Drug: Placebo of Anakinra

Drug: Prednisone