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

Chronic Kidney Disease Clinical Trial

— Ana4CKD  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04844814
• Other study ID #: APHP180560
• Status: Recruiting
• Phase: Phase 2
• Start date: June 2, 2022
• Est. completion date: July 2, 2025

Study information

• Verified date: August 2022
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Hang-Korng EA, PhD-MD
• Phone: 1 49 95 88 25
• Email: hang-korng.ea[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 204
• Est. completion date: July 2, 2025
• Est. primary completion date: June 2, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Gout
• Kidney Diseases
• Renal Insufficiency, Chronic
• Renal Transplantation

Intervention

Drug:
• Anakinra 100Mg/0.67Ml Inj Syringe
Anakinra 100 mg/d subcutaneous injection
• Prednisone
Prednisone 30 mg/d
• Placebo of Prednisone
Placebo of Prednisone
• Placebo of Anakinra
Placebo of Anakinra

Locations

Country	Name	City	State
France	Rhumathology department	Paris	Ile-De-France

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percentage of responders (improvement = 50%) at day 5	Percentage of responders (improvement = 50%) at day 5	Day 5
Secondary	Percentage of flare resolution (improvement = 80%) at day 5	Percentage of flare resolution (improvement = 80%) at day 5	Day 5
Secondary	Time to treatment response	Time to treatment response	Day 3 or Day 5
Secondary	Time to flare resolution	Time to flare resolution	Day 3 or Day 5
Secondary	Treatment duration	Treatment duration	Day3 or Day 5
Secondary	Duration of hospitalization	Duration of hospitalization	Day 3 or Day 5
Secondary	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
Secondary	Healthcare consumption at month 1: total hospital stay	Healthcare consumption at month 1 assessed by total hospital stay	Month 1
Secondary	Healthcare consumption at month 1	Healthcare consumption at month 1 assessed by number and cumulative duration of sick leave related to gout	Month 1
Secondary	Side effects	Side effects	Month 1
Secondary	Comorbidity decompensations at month 1 : DT2 decompensation	Comorbidity decompensations at month 1 assessed by DT2 decompensation measure	Month 1
Secondary	Comorbidity decompensations at month 1: Blood pressure	Comorbidity decompensations at month 1 assessed by Blood pressure measure	Month 1
Secondary	Comorbidity decompensations at month 1: Hypertension	Comorbidity decompensations at month 1 assessed by hypertension measure	Month 1
Secondary	Comorbidity decompensations at month 1: Weight	Comorbidity decompensations at month 1 assessed by Weight measure	Month 1
Secondary	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
Secondary	Comorbidity decompensations at month 1: Blood analysis of serum creatinine level	Comorbidity decompensations at month 1 assessed by serum creatinine level measure	Month 1
Secondary	Comorbidity decompensations at month 1: Blood analysis of epidermal Growth Factor Receptor (eGFR)	Comorbidity decompensations at month 1 assessed by eGFR measure	Month 1
Secondary	Comorbidity decompensations at month 1: Blood analysis of C reactive protein (CRP)	Comorbidity decompensations at month 1 assessed by CRP measure	Month 1
Secondary	Comorbidity decompensations at month 1: Blood analysis of HbA1C	Comorbidity decompensations at month 1 assessed by HbA1C measure	Month 1
Secondary	Comorbidity decompensations at month 1: Blood analysis of total cholesterol	Comorbidity decompensations at month 1 assessed by total cholesterol measure	Month 1
Secondary	Comorbidity decompensations at month 1: Blood analysis of LDL cholesterol	Comorbidity decompensations at month 1 assessed by HDL cholesterol measure	Month 1
Secondary	Comorbidity decompensations at month 1: Blood analysis of HDL cholesterol	Comorbidity decompensations at month 1 assessed by HDL cholesterol measure	Month 1
Secondary	Comorbidity decompensations at month 1: Blood analysis of triglyceride	Comorbidity decompensations at month 1 assessed by triglyceride measure	Month 1
Secondary	Comorbidity decompensations at month 1: Blood analysis of glycaemia	Comorbidity decompensations at month 1 assessed by glycaemia measure	Month 1
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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