The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS
- Registration Number
- NCT00413361
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- Brief Summary
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
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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 543
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A versus hydroxychloroquine placebo B versus hydroxychloroquine versus hydroxychloroquine
- Primary Outcome Measures
Name Time Method 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 The number of patient in each group who developed a flare (according to the SELENA-SLEDAI composite criteria) during the study period.
- Secondary Outcome Measures
Name Time Method The number of patients in each group who developed a flare during the study period. 7 months of follow up The number of patients in each group who developed a flare during the study period.
The total number of flares in each group 7 months of follow up The total number of flares in each group
Treatment tolerance evaluation will include clinical, electrocardiographic and ophthalmologic screening. 7 months of follow up Treatment tolerance evaluation will include clinical, electrocardiographic and ophthalmologic screening.
the total dose of steroids in each group 7 months of follow up the total dose of steroids in each group
the area under the curve of SELENA SLEDAI in each group 7 months of follow up the area under the curve of SELENA SLEDAI in each group
the mean change of the quality of life questionnaire SF-36 7 months of follow up the mean change of the quality of life questionnaire SF-36
the mean change on the score of analogical visual scale in each group 7 months of follow up the mean change on the score of analogical visual scale in each group
Trial Locations
- Locations (2)
Chu Pitie Salpetriere
🇫🇷Paris, France
Hopital la Pitié Salpétrière Assistance Publique
🇫🇷Paris, France