The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS

Overview

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

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: Double (Care Provider, Investigator)
  • Study Primary Completion Date: January 2011

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

Interventions

  • Drug: versus hydroxychloroquine
    • versus hydroxychloroquine

Arms, Groups and Cohorts

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

Clinical Trial Outcome Measures

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
    • The number of patient in each group who developed a flare (according to the SELENA-SLEDAI composite criteria) during the study period.

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

Participating in This Clinical Trial

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: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Assistance Publique – Hôpitaux de Paris
  • Collaborator
    • Sanofi-Synthelabo
  • Provider of Information About this Clinical Study
    • Zakia IDIR, Department Clinical Rechearch of Developpement
  • Overall Official(s)
    • Nathalie COSTEDOAT-CHALUMEAU, MD,, Principal Investigator, Assistance Publique – Hôpitaux de Paris

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