CompletedNCT00413361Updated Jan 27, 2011

The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS

A Phase 4 interventional study of versus hydroxychloroquine in Systemic Lupus Erythematosus, sponsored by Assistance Publique - Hôpitaux de Paris. Completed at 2 sites in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2011-01-27.

Sponsored by Assistance Publique - Hôpitaux de Paris · Phase 4, Interventional, and Prevention

Phase: Phase 4
Study type: Interventional
Enrollment: 543
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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

Read the 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

Conditions studied

Systemic Lupus Erythematosus

Browse trials for

Lupus Erythematosus, Systemic 1,202

Keywords

Systemic Lupus Erythematosus
Hydroxychloroquine

In context

Lupus Erythematosus, Systemic

1,202 studies on the registry are indexed under Lupus Erythematosus, Systemic; 399 are open to participants now.

This study's enrollment of 543 is above the median of 50 across 867 interventional studies indexed under Lupus Erythematosus, Systemic.

Browse Lupus Erythematosus, Systemic studies →

Lead sponsor

Assistance Publique - Hôpitaux de Paris is the lead sponsor of 3,505 studies on the registry; 1,006 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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

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

Phase: Phase 4
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Care provider, Investigator)
Enrollment: 543 participants (actual)

Study arms

Placebo comparator
A
placebo
Drug: versus hydroxychloroquine
Experimental
B
versus hydroxychloroquine
Drug: versus hydroxychloroquine

Interventions

Drugversus hydroxychloroquine
versus hydroxychloroquine

What researchers measure

Primary outcomes

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.
Time frame: 7 months of follow up

Secondary outcomes

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.
Time frame: 7 months of follow up
The total number of flares in each group
The total number of flares in each group
Time frame: 7 months of follow up
the total dose of steroids in each group
the total dose of steroids in each group
Time frame: 7 months of follow up
the area under the curve of SELENA SLEDAI in each group
the area under the curve of SELENA SLEDAI in each group
Time frame: 7 months of follow up
the mean change of the quality of life questionnaire SF-36
the mean change of the quality of life questionnaire SF-36
Time frame: 7 months of follow up
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
Time frame: 7 months of follow up
Treatment tolerance evaluation will include clinical, electrocardiographic and ophthalmologic screening.
Treatment tolerance evaluation will include clinical, electrocardiographic and ophthalmologic screening.
Time frame: 7 months of follow up

Study locations

2 sites

Chu Pitie Salpetriere
Paris, 75013, France
Hopital la Pitié Salpétrière Assistance Publique
Paris, 75013, France

References and documents

Publications

Morris DL, Sheng Y, Zhang Y, Wang YF, Zhu Z, Tombleson P, Chen L, Cunninghame Graham DS, Bentham J, Roberts AL, Chen R, Zuo X, Wang T, Wen L, Yang C, Liu L, Yang L, Li F, Huang Y, Yin X, Yang S, Ronnblom L, Furnrohr BG, Voll RE, Schett G, Costedoat-Chalumeau N, Gaffney PM, Lau YL, Zhang X, Yang W, Cui Y, Vyse TJ. Genome-wide association meta-analysis in Chinese and European individuals identifies ten new loci associated with systemic lupus erythematosus. Nat Genet. 2016 Aug;48(8):940-946. doi: 10.1038/ng.3603. Epub 2016 Jul 11. PubMed 27399966 ↗
Schoindre Y, Jallouli M, Tanguy ML, Ghillani P, Galicier L, Aumaitre O, Frances C, Le Guern V, Liote F, Smail A, Limal N, Perard L, Desmurs-Clavel H, Le Thi Huong D, Asli B, Kahn JE, Sailler L, Ackermann F, Papo T, Sacre K, Fain O, Stirnemann J, Cacoub P, Leroux G, Cohen-Bittan J, Hulot JS, Lechat P, Musset L, Piette JC, Amoura Z, Souberbielle JC, Costedoat-Chalumeau N; Group PLUS. Lower vitamin D levels are associated with higher systemic lupus erythematosus activity, but not predictive of disease flare-up. Lupus Sci Med. 2014 Jun 7;1(1):e000027. doi: 10.1136/lupus-2014-000027. eCollection 2014. PubMed 25379192 ↗
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, Frances C, Guettrot-Imbert G, Harle JR, Lambotte O, Le Guern V, Sene D, Trad S, Vidal E, Sarrot-Reynauld F, Gompel A, Tanguy ML, Touraine P, Lacorte JM, Costedoat-Chalumeau N; PLUS group. Study of anti-Mullerian 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. PubMed 23833039 ↗
Costedoat-Chalumeau N, Galicier L, Aumaitre O, Frances C, Le Guern V, Liote 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, Sacre 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. PubMed 23144449 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jan 27, 2011, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00413361
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Collaborators: Sanofi-Synthelabo
First posted: Dec 19, 2006
Start date: Jun 2007
Primary completion: Jan 2011
Completion: Jan 2011
Last update: Jan 27, 2011

Study contacts

Nathalie COSTEDOAT-CHALUMEAU, MD,

principal investigator · Assistance Publique - Hôpitaux de Paris

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in May 2007. You cannot join it, but the record below documents what was studied.

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