The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS

Study Overview
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Brief Summary
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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

Detailed Description
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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: To define biological and clinical hallmarks present at M1 (month 1) which are predictor of SLE exacerbations in the next 6 month, To establish the parameters of HCQ pharmacokinetic model, by a study of population, using a Bayésienne approach. To study the influence of allelic variants of drug carriers and other genes in the interindividual variability of blood HCQ concentrations. To study the influence of the compliance in the blood HCQ concentration variability To study the relation between blood HCQ concentrations, SLE activity and quality of life To study the relation between blood HCQ concentrations, SLE activity and lipid profile of the patients To study the relation between ECG abnormalities and blood HCQ concentrations To constitute a bank of serum, a DNAbank, and a RNAbank to permit subsequent studies

Official Title
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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

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: versus hydroxychloroquine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 0. 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 Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: A<br>placebo | Drug: versus hydroxychloroquine<br>* versus hydroxychloroquine<br>|
| Experimental: B<br>versus hydroxychloroquine | Drug: versus hydroxychloroquine<br>* versus hydroxychloroquine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of patient in each group who developed a flare (according to the SELENA-SLEDAI composite criteria) during the study period. | The number of patient in each group who developed a flare (according to the SELENA-SLEDAI composite criteria) during the study period. | 7 months of follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of patients in each group who developed a flare during the study period. | 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 | The total number of flares in each group | 7 months of follow up | 
| the total dose of steroids in each group | the total dose of steroids in each group | 7 months of follow up | 
| the area under the curve of SELENA SLEDAI in each group | the area under the curve of SELENA SLEDAI in each group | 7 months of follow up | 
| the mean change of the quality of life questionnaire SF-36 | 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 | the mean change on the score of analogical visual scale in each group | 7 months of follow up | 
| Treatment tolerance evaluation will include clinical, electrocardiographic and ophthalmologic screening. | Treatment tolerance evaluation will include clinical, electrocardiographic and ophthalmologic screening. | 7 months of follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systemic Lupus Erythematosus, Hydroxychloroquine