Official Title: “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”

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

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Caregiver, Investigator), Dose Comparison, Parallel Assignment, Efficacy Study

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

Intervention(s) in this Clinical Trial

• Drug: versus hydroxychloroquine

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: A
  • placebo
• Experimental: B
  • versus hydroxychloroquine

Primary Measures

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

Secondary Measures

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

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Overall Clinical Trial Officials and Contacts

Nathalie COSTEDOAT-CHALUMEAU, MD, Principal Investigator Assistance Publique - Hôpitaux de Paris  

Overall Contact: Nathalie COSTEDOAT-CHALUMEAU, MD +33 (0)-1 42 17 82 48 nathalie.costedoat@psl.aphp.fr

Information obtained from ClinicalTrials.gov on January 08, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00413361

Study ID Number: P051070

ClinicalTrials.gov Identifier: NCT00413361

Health Authority: France: Ministry of Health