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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
History of Changes
  Purpose

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


Condition Intervention Phase
Systemic Lupus Erythematosus
 Drug: versus hydroxychloroquine
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Caregiver, Investigator)
Primary Purpose: Prevention
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

Resource links provided by NLM:

MedlinePlus related topics: Lupus
U.S. FDA Resources

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome 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 ] [ 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 543
Study Start Date: June 2007
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: A
placebo
 Drug: versus hydroxychloroquine
versus hydroxychloroquine
Other Name: versus hydroxychloroquine
Experimental: B
versus hydroxychloroquine
 Drug: versus hydroxychloroquine
versus hydroxychloroquine
Other Name: versus hydroxychloroquine

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
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00413361

Locations
France
Chu Pitie Salpetriere
Paris, France, 75013
Hopital la Pitié Salpétrière Assistance Publique
Paris, France, 75013
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Sanofi-Synthelabo
Investigators
Principal Investigator: Nathalie COSTEDOAT-CHALUMEAU, MD, Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Zakia IDIR, Department Clinical Rechearch of Developpement
ClinicalTrials.gov Identifier: NCT00413361     History of Changes
Other Study ID Numbers: P051070
Study First Received: December 18, 2006
Last Updated: January 26, 2011
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Systemic Lupus Erythematosus
Hydroxychloroquine

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Hydroxychloroquine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
 Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on June 18, 2013