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The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00413361
Recruitment Status : Completed
First Posted : December 19, 2006
Last Update Posted : January 27, 2011
Sponsor:
Collaborator:
Sanofi-Synthelabo
Information provided by:
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date  ICMJE December 18, 2006
First Posted Date  ICMJE December 19, 2006
Last Update Posted Date January 27, 2011
Study Start Date  ICMJE June 2007
Actual Primary Completion Date January 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 26, 2011)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 18, 2006)
  • The number of patient in each group who developed a flare
  • (according to the SELENA-SLEDAI composite criteria) during the study period.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 26, 2011)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 18, 2006)
  • The number of patients in each group who developed a flare during the study period.
  • The total number of flares in each group
  • the total dose of steroids in each group
  • the area under the curve of SELENA SLEDAI in each group
  • the mean change of the quality of life questionnaire SF-36
  • the mean change on the score of analogical visual scale in each group
  • Treatment tolerance evaluation will include clinical, electrocardiographic and ophthalmologic screening.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS
Official Title  ICMJE 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
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Care Provider, Investigator)
Primary Purpose: Prevention
Condition  ICMJE Systemic Lupus Erythematosus
Intervention  ICMJE Drug: versus hydroxychloroquine
versus hydroxychloroquine
Study Arms  ICMJE
  • Placebo Comparator: A
    placebo
    Intervention: Drug: versus hydroxychloroquine
  • Experimental: B
    versus hydroxychloroquine
    Intervention: Drug: versus hydroxychloroquine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 26, 2011)
543
Original Enrollment  ICMJE
 (submitted: December 18, 2006)
800
Actual Study Completion Date  ICMJE January 2011
Actual Primary Completion Date January 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00413361
Other Study ID Numbers  ICMJE P051070
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Zakia IDIR, Department Clinical Rechearch of Developpement
Study Sponsor  ICMJE Assistance Publique - Hôpitaux de Paris
Collaborators  ICMJE Sanofi-Synthelabo
Investigators  ICMJE
Principal Investigator: Nathalie COSTEDOAT-CHALUMEAU, MD, Assistance Publique - Hôpitaux de Paris
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date May 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP