The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS

Assistance Publique - Hôpitaux de Paris

Status and phase

Completed

Phase 4

Conditions

Systemic Lupus Erythematosus

Treatments

Drug: versus hydroxychloroquine

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00413361

P051070

Details and patient eligibility

About

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 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

Enrollment

543 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.