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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Disease; Gout; Renal Transplantation
• Intervention / Treatment: Drug: Anakinra 100Mg/0.67Ml Inj Syringe; Drug: Placebo of Prednisone; Drug: Prednisone; Drug: Placebo of Anakinra

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.

• Study Type: Interventional
• Enrollment (Anticipated): 204
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hang-Korng EA, PhD-MD; Phone Number: +33 1 49 95 88 25; Email: hang-korng.ea@aphp.fr

Study Locations

• France
  • Ile-De-France
    • Paris, Ile-De-France, France, 75010
      • Recruiting
      • Rhumathology department
      • Contact: Hang-Korng Pr EA, PHPU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anakinra; Anakinra 100 mg/d+Placebo of Prednisone	Drug: Anakinra 100Mg/0.67Ml Inj Syringe; Anakinra 100 mg/d subcutaneous injection; Drug: Placebo of Prednisone; Placebo of Prednisone
Active Comparator: Prednisone; Prednisone 30 mg/d+Placebo of Anakinra	Drug: Prednisone; Prednisone 30 mg/d; Drug: Placebo of Anakinra; Placebo of Anakinra

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Hang-Korng EA, PhD-MD, Hôpital Lariboisière

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2022
• Primary Completion (Anticipated): June 2, 2025
• Study Completion (Anticipated): July 2, 2025

Study Registration Dates

• First Submitted: January 24, 2021
• First Submitted That Met QC Criteria: April 13, 2021
• First Posted (Actual): April 14, 2021

Study Record Updates

• Last Update Posted (Actual): August 23, 2022
• Last Update Submitted That Met QC Criteria: August 22, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Chronic kidney disease; Corticosteroid; Gout; Urate crystals; Renal transplantation; Anakinra; Flare; IL-1b
• Additional Relevant MeSH Terms: Metabolic Diseases; Urologic Diseases; Renal Insufficiency; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Metabolism, Inborn Errors; Crystal Arthropathies; Purine-Pyrimidine Metabolism, Inborn Errors; Kidney Diseases; Renal Insufficiency, Chronic; Gout; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone; Interleukin 1 Receptor Antagonist Protein
• Other Study ID Numbers: APHP180560

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No