Study of the Reduction of Systemic Lupus Erythematosus Flares Through Adaptation of the Dosage of Hydroxychloroquine to Its Whole-blood Concentration. National Multicenter Randomized Prospective Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 543
- 试验地点
- 2
- 主要终点
- The number of patient in each group who developed a flare (according to the SELENA-SLEDAI composite criteria) during the study period.
研究概览
简要总结
The main objective of study PLUS is to determine the potential benefits of individualized HCQ dosing schedules aimed at maintaining the whole-blood HCQ concentration above 1000 ng/ml
详细描述
Hydroxychloroquine (HCQ) is a treatment which allows preventing Systemic Lupus Erythematosus (SLE) exacerbations.
HCQ can be measured in whole-blood by HPLC (High Performance Liquid Chromatography).
Interindividual variability in blood HCQ concentrations is important and a correlation between HCQ level and clinical efficacy of HCQ has been demonstrated in SLE in a monocentric study of 143 unselected SLE patients.
The main objective of study PLUS is to determine the potential benefits of individualized HCQ dosing schedules aimed at maintaining the whole-blood HCQ concentration above 1000 ng/ml
The secondary objectives are:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Care Provider, Investigator)
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
- •Age of 18 and above
- •Diagnosis of Systemic Lupus Erythematosus (SLE) according to the American College of Rheumatology (ACR) Classification Criteria.
- •Treatment with HCQ for at least 6 months, without modification of HCQ dosage for 2 months
- •Stable dosage of HCQ from one day to another (200 g x 2/day or 400 mg once a day or 200 mg once a day)
- •No increase in the steroids dosage during the 3 previous weeks
- •Steroids dosage lower or equal to
- •5 mg/kg/day of prednisone equivalent
- •No modifications of a possible immunosuppressor during the 2 previous months
- •SELENA-SLEDAI < or = 12
- •Signature of the consent of participation
排除标准
- •Known retinopathy, present or passed
- •Severe cataract obstructing the ophthalmologic monitoring
- •MONOPHTALM patients
- •Past history of intolerance with HCQ (in particular gastro-intestinal, or retinal) during the possible former use of a higher dosage
- •Use of nivaquine during the 3 previous months
- •Treatment with biotherapy (for example Rituximab) during the 12 previous months
- •Calculated clearance of creatinin lower than 60 ml/min
- •Chronic alcoholism
- •Liver failure
- •Desire of pregnancy in the next 7 months
- •Known non compliance, and risks of random follow-up
- •Absence of social security cover
- •People profiting from a particular protection:
- •Pregnant women
- •Age under 18
- •Patient under supervision and TRUSTEESHIP
- •People who are hospitalized without their consent and not protected by the law
- •People who are private of freedom.
- •Criteria of inclusion at the visit of randomization (D0):
- •All the patients responding to the next criterions can be randomized:
- •Blood HCQ concentration ranging between 100 and 750 ng/ml at the time of the visit of preselection,
- •No increase in the steroids dosage since last visit
- •No modifications of a possible immunosuppressor since last visit
- •SELENA-SLEDAI < or = 12 Activity of the lupus remaining stable (no increase of more than 2 points of the SELENA-SLEDAI),
- •Ophthalmologic examination in the 6 previous months with no contra-indication for the use of HCQ,
- •Absences of conductive disorders on the ECG
- •Use of an effective contraception,
- •Negative Beta-HCG.
研究组 & 干预措施
A
placebo
干预措施: versus hydroxychloroquine (Drug)
B
versus hydroxychloroquine
干预措施: versus hydroxychloroquine (Drug)
结局指标
主要结局
The number of patient in each group who developed a flare (according to the SELENA-SLEDAI composite criteria) during the study period.
时间窗: 7 months of follow up
The number of patient in each group who developed a flare (according to the SELENA-SLEDAI composite criteria) during the study period.
次要结局
- The number of patients in each group who developed a flare during the study period.(7 months of follow up)
- The total number of flares in each group(7 months of follow up)
- the mean change of the quality of life questionnaire SF-36(7 months of follow up)
- the mean change on the score of analogical visual scale in each group(7 months of follow up)
- the total dose of steroids in each group(7 months of follow up)
- the area under the curve of SELENA SLEDAI in each group(7 months of follow up)
- Treatment tolerance evaluation will include clinical, electrocardiographic and ophthalmologic screening.(7 months of follow up)