The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS - Full Text View

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:

Genetics Home Reference related topics: systemic lupus erythematosus

MedlinePlus related topics: Lupus

Drug Information available for: Hydroxychloroquine Hydroxychloroquine sulfate

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
Experimental: B versus hydroxychloroquine	Drug: versus hydroxychloroquine 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 (Adult, Senior)
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Morel N, Bachelot A, Chakhtoura Z, Ghillani-Dalbin P, Amoura Z, Galicier L, Aumaitre O, Piette JC, Pourrat J, Boutin D, Sacre K, Kahn JE, Duhaut P, Farge D, Francès C, Guettrot-Imbert G, Harlé JR, Lambotte O, Le Guern V, Sène D, Trad S, Vidal E, Sarrot-Reynauld F, Gompel A, Tanguy ML, Touraine P, Lacorte JM, Costedoat-Chalumeau N; PLUS group. Study of anti-Müllerian hormone and its relation to the subsequent probability of pregnancy in 112 patients with systemic lupus erythematosus, exposed or not to cyclophosphamide. J Clin Endocrinol Metab. 2013 Sep;98(9):3785-92. doi: 10.1210/jc.2013-1235. Epub 2013 Jul 5.

Costedoat-Chalumeau N, Galicier L, Aumaître O, Francès C, Le Guern V, Lioté F, Smail A, Limal N, Perard L, Desmurs-Clavel H, Boutin du LT, Asli B, Kahn JE, Pourrat J, Sailler L, Ackermann F, Papo T, Sacré K, Fain O, Stirnemann J, Cacoub P, Jallouli M, Leroux G, Cohen-Bittan J, Tanguy ML, Hulot JS, Lechat P, Musset L, Amoura Z, Piette JC; Group PLUS. Hydroxychloroquine in systemic lupus erythematosus: results of a French multicentre controlled trial (PLUS Study). Ann Rheum Dis. 2013 Nov;72(11):1786-92. doi: 10.1136/annrheumdis-2012-202322. Epub 2012 Nov 10.


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 Antimalarials	Antiprotozoal Agents Antiparasitic Agents Anti-Infective Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antirheumatic Agents

ClinicalTrials.gov processed this record on September 23, 2016