Non-inferiority Study of a New Therapeutic Strategy for Gout: Immediate Prescription of a Hypouricemic Treatment, Febuxostat, Compared to Its Delayed Administration - FEFACRIGOU Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 128
- 试验地点
- 6
- 主要终点
- To compare the number of days with gout at 42 days +/- 3 days (W6) in patients with an early administration of febuxostat from the acute attack compared to patients with a delayed administration of febuxostat by 6 weeks after the acute attack.
研究概览
简要总结
Gout, the most common inflammatory rheumatism in France, is a complication of chronic hyperuricemia (> 360umol / l). The resulting urate crystals are deposited in many tissues, especially the skeletal or kidneys. It appears in the form of spontaneously regressive inflammatory joint attacks in 5 to 7 days but recurrent. Gout turns into a chronic disease if uric acidemia is not reduced, and is responsible for joint destruction. It becomes a vector of renal failure and is associated with cardiovascular morbidity and a reduction in life expectancy. It is cured if a long-term treatment such as febuxostat leading to the normalization of the uric acidemia is administered.
However, the frequency of this disease is increasing in industrialized or emerging countries. The causes are numerous, particularly food, but also related to flaws in therapeutic care. Studies show that this treatment is not taken in particular because, after the acute attack, the patient who has become asymptomatic again no longer consults. Currently, in a traditional way and according to European recommendations, it is not prescribed until several weeks after the acute attack in order to avoid early relapses, which would then be more numerous. Nevertheless, even if the hypouricemic agent is prescribed late , the attacks can be repeated and become rare for several months after obtaining a uricemia below 360umol / l; they eventually disappear. Lack of knowledge of this disease largely affects the hazards of disease-modifying treatment, which alone can prevent the progression to chronic inflammatory disease and its cardiovascular and renal impact and on mortality. One of the causes of not taking a hypouricemic agent is its delayed administration.
This study is proposed to assess the relevance of early initiation versus delayed administration of such treatment.
详细描述
This is a non-inferiority study comparing immediate administration with 6 weeks delayed administration of febuxostat at a dose of 80 mg / day. The methodology of non-inferiority is what we want to show. Indeed, the immediate initiation of a hypo-uricemic agent is currently considered as an aggravating factor with respect to the duration or the risks of early relapse of the crisis, without this being supported by precise studies. The basic treatment is beneficial in the long term: by normalizing uricemia, it controls gouty disease. We want to show that the early introduction is as well tolerated as its abstention which is the current recommendation.
The diagnosis of gout attack is based on recently established American-European criteria.
The choice of the hyporuricemic molecule is febuxostat, on the one hand because of a greater potency of action than allopurinol at the available dosages, which should make it possible to obtain a clear reduction in uraemia (of approximately 40%) and on the other hand easy to use - without dose adjustment - in patients with renal insufficiency with a creatinine clearance greater than 30 ml / min.
The number of patients participating in the study is set at 128, which is higher than the published prospective studies. Patients will be randomized (in order of succession when entering the study) into 2 groups, the first receiving febuxostat immediately for 6 weeks, the second receiving no immediate febuxostat treatment - which corresponds to current practice.
This study covers several periods:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 Where Postmenopausal woman: amenorrhea not medically induced for at least 12 months before the inclusion visit.
排除标准
- •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
- •Any history of pre-existing major cardiovascular disease (myocardial infarction, stroke, unstable angina, etc.), metabolic, endocrine, psychiatric or cancerous in uncontrolled development,
- •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.
研究组 & 干预措施
Experimental arm
Immediate prescription (at randomization) of ADENURIC 80 mg / day (febuxostat), urate-lowering treatment, for a period of 2 x 6 weeks.
干预措施: Adenuric (Drug)
结局指标
主要结局
To compare the number of days with gout at 42 days +/- 3 days (W6) in patients with an early administration of febuxostat from the acute attack compared to patients with a delayed administration of febuxostat by 6 weeks after the acute attack.
时间窗: 6 weeks
number of days with gout at 42 days (S6) assessed by the daily booklet given to the patient, allowing him to inform daily whether he has suffered from gout or not
次要结局
- To compare, in patients with early administration of febuxostat compared to patients with delayed administration the tolerance of treatment during the study (until 26 weeks)(During the study (from the randomisation to 26 weeks))
- To compare, in patients with early administration of febuxostat compared to patients with delayed administration the function of the patient during the study (until 26 weeks)(During the study (from the randomisation to 26 weeks))
- To compare, in patients with early administration of febuxostat compared to patients with delayed administration the intensity of pain during the study (until 26 weeks)(During the study (from the randomisation to 26 weeks))