The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS

This study has been completed.
Sponsor:
Collaborator:
Sanofi-Synthelabo
Information provided by:
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00413361
First received: December 18, 2006
Last updated: January 26, 2011
Last verified: May 2007

December 18, 2006
January 26, 2011
June 2007
January 2011   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: No ]
The number of patient in each group who developed a flare (according to the SELENA-SLEDAI composite criteria) during the study period.
  • (according to the SELENA-SLEDAI composite criteria) during the study period.
  • The number of patient in each group who developed a flare
Complete list of historical versions of study NCT00413361 on ClinicalTrials.gov Archive Site
  • The number of patients in each group who developed a flare during the study period. [ Time Frame: 7 months of follow up ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    The total number of flares in each group
  • the total dose of steroids in each group [ Time Frame: 7 months of follow up ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Treatment tolerance evaluation will include clinical, electrocardiographic and ophthalmologic screening.
  • 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.
Not Provided
Not Provided
 
The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS
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

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
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Caregiver, Investigator)
Primary Purpose: Prevention
Systemic Lupus Erythematosus
Drug: versus hydroxychloroquine
versus hydroxychloroquine
Other Name: versus hydroxychloroquine
  • Placebo Comparator: A
    placebo
    Intervention: Drug: versus hydroxychloroquine
  • Experimental: B
    versus hydroxychloroquine
    Intervention: Drug: versus hydroxychloroquine

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
543
January 2011
January 2011   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT00413361
P051070
Yes
Zakia IDIR, Department Clinical Rechearch of Developpement
Assistance Publique - Hôpitaux de Paris
Sanofi-Synthelabo
Principal Investigator: Nathalie COSTEDOAT-CHALUMEAU, MD, Assistance Publique - Hôpitaux de Paris
Assistance Publique - Hôpitaux de Paris
May 2007

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