Evaluation of Immediate Versus Deferred Febuxostat Administration in Gout Management: A Non-Inferiority Clinical Trial

Trial ID: 2024-515547-34-00
Protocol: 2017/0386/HP
Sponsor: Centre Hospitalier Universitaire Rouen

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Diseases & Conditions

Gout

Objectives

The primary objective of this study is to evaluate the **number of days with gout** at 42 days ± 3 days (S6) in patients receiving early administration of febuxostat from the acute attack compared to those with delayed administration by 6 weeks post-acute attack. This is clinically relevant as it aims to determine the efficacy of immediate versus deferred treatment in managing gout symptoms, potentially influencing treatment protocols for better patient outcomes.

Secondary objectives include assessing: - **Pain intensity** at 14 (S2), 42 (S6), 84 (S12), and 182 (S26) days, - **Patient function** at the same intervals, - **Treatment tolerance** at these time points, - Occurrence of one or more new **gout attacks** at 14 (S2), 42 (S6), 84 (S12), and 182 (S26) days, - **Number of days with gout** at 14 (S2), 84 (S12), and 182 (S26) days. These secondary objectives provide a comprehensive evaluation of the treatment's impact on various aspects of patient health and quality of life over time.

Participants

The clinical trial involves participants diagnosed with **gout**, specifically those experiencing an acute attack of the condition. The study population includes both male and female subjects, aged 18 years and older, with a creatinine clearance of at least 30 ml/min. Participants are required to have a uricemia level of 420 µmol/l or higher, even if under diuretic treatment. The trial includes individuals who have experienced either a first gout crisis or a new attack of gout not treated with a hypo-uricemic agent for at least six months. Women of childbearing potential must use effective contraception and have a negative urine pregnancy test at inclusion and throughout the study. Postmenopausal women must have experienced amenorrhea for at least 12 months prior to inclusion. The trial population was selected based on these criteria, and participants must be affiliated with a social security scheme. The sponsor has not provided information regarding the total number of participants in the study.

Plans and Procedures

The clinical trial is designed to evaluate the efficacy of **febuxostat** in the treatment of **gout** through a non-inferiority study comparing immediate versus deferred administration. This trial employs a randomized, double-blind, controlled methodology to ensure unbiased results. The trial is expected to span approximately four years, with an estimated end date in May 2027. Participants will be involved for a maximum of 45 days, with the primary endpoint being the number of days with gout at 42 days, assessed through a daily logbook. Secondary endpoints include pain measurement, functional assessment via HAQ and SF36 questionnaires, treatment tolerance, and the number of relapses.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is confirmed based on criteria such as age, uricemia levels, and creatinine clearance. Following the initial visit, participants will attend follow-up visits at 14, 42, 84, and 182 days to monitor pain, functional status, and treatment tolerance. The end-of-study visit will occur at 182 days, marking the conclusion of participant involvement. Conditions that may lead to early termination from the study include non-compliance with the protocol, withdrawal of consent, or adverse events that compromise participant safety.

Treatment

The clinical trial involves the administration of **Febuxostat Viatris 80 mg film-coated tablets** as the experimental medication. Febuxostat is a chemical substance used in the treatment of gout, specifically targeting hyperuricemia. The pharmaceutical form of the medication is a film-coated tablet, designed for oral administration. Each tablet contains 80 mg of the active substance, febuxostat. The maximum daily dose is set at 80 mg, with a total maximum dose of 3600 mg over the course of the treatment period. The treatment duration is limited to a maximum of 45 days. Participants are required to take the medication orally, adhering to the prescribed dosage and schedule to ensure compliance and efficacy.

In this study, the experimental treatment is compared to a deferred administration strategy, which serves as the comparator treatment. The trial aims to evaluate the non-inferiority of immediate febuxostat administration compared to its delayed use, initiated six weeks after an acute gout attack. The study does not involve the use of a placebo or any additional non-experimental treatments. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol and to accurately assess the treatment's effectiveness.

Efficacy

Efficacy in this clinical trial will be assessed primarily by measuring the number of days with **gout** at 42 days (S6). This will be evaluated using a daily logbook provided to participants, allowing them to record daily occurrences of gout symptoms. Secondary endpoints include pain assessment using the EVA centimetric scale at 14 (S2), 42 (S6), 84 (S12), and 182 (S26) days, as well as scores from the HAQ and SF36 questionnaires at specified intervals to evaluate patient function. Additionally, treatment tolerance will be assessed by recording the number of adverse events at the same timepoints. The number of relapses, defined by specific criteria, will also be monitored at these intervals. The efficacy parameters will be collected and analyzed according to the schedule outlined, ensuring a comprehensive evaluation of the treatment's impact on gout management.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Patients with an attack of gout, diagnosed immediately or less than 5 days old. Gout is defined according to American-European criteria (Appendix 3).
Attack of gout affecting one (or more) peripheral joint (s) whatever (s) it (s): • Either a first crisis, • Either a new attack of a gout not treated with a hypo-uricemic or for which the hypo-uricemic treatment has not been taken for at least 6 months.
Uricemia ≥ 420 μmol / l, including under a diuretic (dosage carried out within 10 days before inclusion),
Age ≥ 18 years old
Patient with a creatinine clearance ≥ 30 ml / min (dosage carried out within 10 days before inclusion)
Patient having read and understood the information letter and signed the consent form
Affiliation to a social security scheme
Woman of childbearing potential with effective contraception according to WHO definition (estrogen-progestins or intrauterine device or tubal ligation for more than 1 month and to be continued for at least 5 weeks after the last dose of the drug. ) and a negative urine pregnancy test on inclusion and throughout the duration of the study.
Postmenopausal woman: amenorrhea not medically induced for at least 12 months before the inclusion visit.

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Exclusion Criteria

Patients under the age of 18
Stop taking a hypouricemic agent for less than 6 months
Known contraindication to ADENURIC 80 mg film-coated tablet: hypersensitivity to the active substance (febuxostat) or to one of the excipients
Renal failure defined by creatinine clearance <30 ml / min
Hepatic disease defined by an increase to more than 2 times the normal of transaminases, alkaline phosphatases, to more than 3 times the normal of gamma-GT
Non-weaned alcoholism
Crisis more than 5 days old
Patient who has received an organ or marrow transplant
Person on Naproxen, mercaptopurine, azathioprine, Glycuronidation inhibitors and inducers, theophylline, macrolides, HMG Co-A reductase inhibitors and / or diuretic in combination with an ACE inhibitor or ARAII
Person with rare hereditary disorders of galactose intolerance, lactase deficiency or glucose / galactose malabsorption
Poor understanding of the project due to neurological disease or lack of French practice
Pregnant woman or likely to be in the absence of effective contraception (Women of childbearing age should have a negative urine pregnancy test)
Breastfeeding woman
All pre-existing diseases listed below: - Cardiovascular diseases: any manifestation associated with heart failure (exertional dyspnea stage III-IV and BNP correlated with age >=3N and ejection fraction < 40%), unstable angina and/or coronary syndrome or myocardial necrosis less than 1 month old, arteritis of the lower limbs stage 3- 4, uncontrolled hypertension; - Neurological diseases: amyotrophic lateral sclerosis or progressive MS, any dementia syndrome, confusional syndrome, any intellectual disability and recent stroke (less than 4 weeks old); - Endocrine and metabolic diseases: uncontrolled hyperthyroidism, severe untreated hypothyroidism, Cushing's disease, endocrine polyadenomatosis, insulin-dependent or non-decompensated diabetes: ketoacidosis, hyperosmolarity; - Liver diseases: hepatocellular insufficiency (TP < 60, albuminemia < 30 g/l); - Pulmonary diseases: any severe respiratory insufficiency requiring oxygen therapy of any daily duration; any alveolo-interstitial pathology, whether treated or not; - Ongoing cancer or haematological diseases under active treatment, with the exception of hormonal treatments; - Severe psychiatric disorders which have not stabilized and which may interfere with understanding of the protocol, reduce compliance with treatment and have a negative impact on the quality of adverse event data; - Active autoimmune diseases, such as lupus or certain vasculitides, which are prone to multisystemic complications and often require immunosuppressive therapy.
Person deprived of liberty by an administrative or judicial decision
Person placed under judicial protection, guardianship or curatorship
Participating patient who participated in the month preceding inclusion in another interventional drug trial