The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS

Systemic Lupus Erythematosus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00413361
• Other study ID #: P051070
• Status: Completed
• Phase: Phase 4
• First received: December 18, 2006
• Last updated: January 26, 2011
• Start date: June 2007
• Est. completion date: January 2011

Study information

• Verified date: May 2007
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 543
• Est. completion date: January 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Drug:
• versus hydroxychloroquine
versus hydroxychloroquine

Locations

Country	Name	City	State
France	Chu Pitie Salpetriere	Paris
France	Hopital la Pitié Salpétrière Assistance Publique	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Sanofi-Synthelabo

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The number of patient in each group who developed a flare (according to the SELENA-SLEDAI composite criteria) during the study period.	The number of patient in each group who developed a flare (according to the SELENA-SLEDAI composite criteria) during the study period.	7 months of follow up	No
Secondary	The number of patients in each group who developed a flare during the study period.	The number of patients in each group who developed a flare during the study period.	7 months of follow up	No
Secondary	The total number of flares in each group	The total number of flares in each group	7 months of follow up	No
Secondary	the total dose of steroids in each group	the total dose of steroids in each group	7 months of follow up	No
Secondary	the area under the curve of SELENA SLEDAI in each group	the area under the curve of SELENA SLEDAI in each group	7 months of follow up	No
Secondary	the mean change of the quality of life questionnaire SF-36	the mean change of the quality of life questionnaire SF-36	7 months of follow up	No
Secondary	the mean change on the score of analogical visual scale in each group	the mean change on the score of analogical visual scale in each group	7 months of follow up	No
Secondary	Treatment tolerance evaluation will include clinical, electrocardiographic and ophthalmologic screening.	Treatment tolerance evaluation will include clinical, electrocardiographic and ophthalmologic screening.	7 months of follow up	No