Randomized Multicenter Double-Blind Trial of Anakinra vs. Prednisone for Gout Flare in Chronic Kidney Disease Stages 3b-5 or Post-Transplant Patients

The primary objective of this study is to demonstrate the superiority of **anakinra**, a recombinant agonist of the interleukin-1 antagonist, compared to prednisone in the treatment of gout attacks in patients with chronic kidney disease stages 3b, 4, or 5, renal transplantation, or dialysis. This is clinically relevant as it aims to provide a more effective treatment option for managing gout flares in a population with compromised renal function, where treatment options are often limited due to potential nephrotoxicity.

Secondary objectives include evaluating the efficacy of anakinra by comparing: - Changes in pain from baseline to day 5 - Speed of resolution of attacks (defined as >80% improvement or pain less than 20) - Treatment response time (more than 50% improvement) - Duration of treatment - Number of responders (improvement at day 3) - Number of relapses during the study month - Consumption of care during the study month, including length of hospital stay, use of analgesics, and length of time off work

Additionally, the study will assess the tolerance of anakinra by comparing: - Injection-site reactions - Decreases in neutrophils or platelets - Decompensation of comorbidities such as hypertension, diabetes, dyslipidemia, obesity, and chronic kidney disease - Cardiovascular events including myocardial infarction, arrhythmia, heart failure relapse, and stroke - Incidence of severe infections

The clinical trial involves **men and women** over the age of 18 who are experiencing **renal failure** at stages 3b, 4, or 5, have undergone renal transplantation, or are on dialysis, and are suffering from an untreated **gout attack**. The sponsor has not provided the total number of participants. The study population was selected based on specific criteria, including a confirmed gout attack through urate crystal analysis, ultrasound, or meeting the Nijmegen criteria with a score greater than 8 out of 13. Participants must have chronic kidney disease at the specified stages, be affiliated with the French social security system or CMU, and have signed informed consent. Premenopausal women are required to have a negative plasma pregnancy test and use effective contraception. The trial does not include a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are mentioned.

The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the efficacy and safety of **anakinra** compared to **prednisone** in treating gout flares in patients with chronic kidney disease stages 3b, 4, or 5, or those who have undergone kidney transplantation. The trial will involve adult participants over 18 years of age who meet specific inclusion criteria, such as having a confirmed gout attack and chronic kidney disease. The study aims to demonstrate the superiority of anakinra, a recombinant interleukin-1 antagonist, over prednisone in this patient population.

The trial is expected to last until July 2025, with recruitment having started in June 2022. Participants will be involved in the study for a maximum treatment period of 5 days. The trial includes several key visits: an initial screening visit to confirm eligibility, followed by treatment visits where participants will receive either anakinra or prednisone, and a placebo as appropriate. Follow-up visits will assess the primary endpoint, which is the change in pain from baseline to three days after treatment initiation. Secondary endpoints include the efficacy of anakinra in terms of pain reduction, speed of resolution of attacks, and treatment response time, as well as the assessment of safety and tolerability.

Participants will be monitored for any adverse events, and conditions such as severe infections or significant changes in neutrophil or platelet counts may lead to early termination from the study. The study will also evaluate the number of relapses and the consumption of healthcare resources during the study period. The trial is conducted under strict ethical guidelines, and all participants are required to provide informed consent before enrollment. The study's design ensures that neither the participants nor the investigators know which treatment is being administered, maintaining the integrity of the double-blind methodology.

The clinical trial involves the administration of **CORTANCYL 20 mg**, a **prednisone**-based medication, in the form of a **tablet**. The tablets are scored, allowing for precise dosing adjustments. Prednisone is a synthetic glucocorticoid with anti-inflammatory properties, commonly used in the management of various inflammatory conditions. In this study, the medication is administered orally with a maximum daily dose of 30 mg and a total maximum dose of 150 mg over a treatment period of up to 5 days. The pharmaceutical product is manufactured by CHEPLAPHARM ARZNEIMITTEL GMBH and is authorized for use in France.

The trial also includes the use of **Kineret 100 mg/0.67 ml**, a solution for injection containing **anakinra**, a recombinant interleukin-1 receptor antagonist. This medication is provided in pre-filled syringes for subcutaneous injection. Anakinra is utilized for its ability to modulate inflammatory responses, particularly in conditions such as rheumatoid arthritis. The maximum daily dose is 100 mg, with a total maximum dose of 500 mg over a 5-day treatment period. The product is manufactured by SWEDISH ORPHAN BIOVITRUM AB (PUBL) and is authorized for use in Iceland.

In addition to the active treatments, the study employs a **placebo** of Cortancyl 20 mg, which is designed to mimic the appearance of the active prednisone tablets but contains no active pharmaceutical ingredient. This placebo is used to maintain the double-blind nature of the trial, ensuring unbiased results.

Furthermore, a **placebo** for Kineret is utilized, consisting of a 0.9% sodium chloride (NaCl) solution. This placebo is administered in a manner identical to the active anakinra solution, serving as a control to evaluate the efficacy of the active treatment. The use of placebos in this trial is critical for assessing the true therapeutic effects of the experimental medications.

Efficacy in this clinical trial will be assessed through both primary and secondary endpoints. The primary endpoint focuses on the change in pain levels between the day of inclusion and three days after the initiation of treatment (D3), or the day of discharge from hospitalization if it occurs before D3. This will provide a direct measure of the treatment's immediate impact on pain relief.

Secondary endpoints will further evaluate the efficacy of **anakinra** by comparing various parameters. These include changes in pain from baseline to day 5 (D5), the speed of resolution of gout attacks (defined as more than 80% improvement or pain less than 20 mm), and the treatment response time (more than 50% improvement). Additionally, the duration of treatment, the number of responders showing improvement at D3, and the number of relapses during the study month will be assessed. The study will also compare the consumption of care, including the length of hospital stay, use of analgesics, and time off work.

Furthermore, the trial will assess the tolerance of anakinra by comparing injection-site reactions, decreases in neutrophils or platelets, severe infections, and the decompensation of comorbidities such as hypertension, diabetes, dyslipidemia, obesity, and chronic kidney disease. Cardiovascular events, including myocardial infarction, arrhythmia, heart failure relapse, and stroke, will also be monitored to ensure comprehensive safety profiling.