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The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS

Primary Purpose

Systemic Lupus Erythematosus

Status

Completed

Phase

Phase 4

Locations

France

Study Type

Interventional

Intervention

versus hydroxychloroquine

About this trial

This is an interventional prevention trial for Systemic Lupus Erythematosus focused on measuring Systemic Lupus Erythematosus, Hydroxychloroquine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Chu Pitie Salpetriere
Hopital la Pitié Salpétrière Assistance Publique

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Arm Description

placebo

versus hydroxychloroquine

Outcomes

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.

Secondary Outcome Measures

The number of patients in each group who developed a flare during the study period.

The total number of flares in each group

the total dose of steroids in each group

the area under the curve of SELENA SLEDAI in each group

the mean change of the quality of life questionnaire SF-36

the mean change on the score of analogical visual scale in each group

Treatment tolerance evaluation will include clinical, electrocardiographic and ophthalmologic screening.

Full Information

NCT ID

NCT00413361

First Posted

December 18, 2006

Last Updated

January 26, 2011

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

Sanofi-Synthelabo

1. Study Identification

Unique Protocol Identification Number

NCT00413361

Brief Title

The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2007

Overall Recruitment Status

Completed

Study Start Date

June 2007 (undefined)

Primary Completion Date

January 2011 (Actual)

Study Completion Date

January 2011 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

Sanofi-Synthelabo

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Systemic Lupus Erythematosus

Keywords

Systemic Lupus Erythematosus, Hydroxychloroquine

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

Care ProviderInvestigator

Allocation

Randomized

Enrollment

543 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Placebo Comparator

Arm Description

placebo

Arm Title

Arm Type

Experimental

Arm Description

versus hydroxychloroquine

Intervention Type

Drug

Intervention Name(s)

versus hydroxychloroquine

Intervention Description

versus hydroxychloroquine

Primary Outcome Measure Information:

Title

The number of patient in each group who developed a flare (according to the SELENA-SLEDAI composite criteria) during the study period.

Description

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 Outcome Measure Information:

Title

The number of patients in each group who developed a flare during the study period.

Description

The number of patients in each group who developed a flare during the study period.

Time Frame

7 months of follow up

Title

The total number of flares in each group

Description

The total number of flares in each group

Time Frame

7 months of follow up

Title

the total dose of steroids in each group

Description

the total dose of steroids in each group

Time Frame

7 months of follow up

Title

the area under the curve of SELENA SLEDAI in each group

Description

the area under the curve of SELENA SLEDAI in each group

Time Frame

7 months of follow up

Title

the mean change of the quality of life questionnaire SF-36

Description

the mean change of the quality of life questionnaire SF-36

Time Frame

7 months of follow up

Title

the mean change on the score of analogical visual scale in each group

Description

the mean change on the score of analogical visual scale in each group

Time Frame

7 months of follow up

Title

Treatment tolerance evaluation will include clinical, electrocardiographic and ophthalmologic screening.

Description

Treatment tolerance evaluation will include clinical, electrocardiographic and ophthalmologic screening.

Time Frame

7 months of follow up

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nathalie COSTEDOAT-CHALUMEAU, MD,

Organizational Affiliation

Assistance Publique - Hôpitaux de Paris

Official's Role

Principal Investigator

Facility Information:

Facility Name

Chu Pitie Salpetriere

City

Paris

ZIP/Postal Code

75013

Country

France

Facility Name

Hopital la Pitié Salpétrière Assistance Publique

City

Paris

ZIP/Postal Code

75013

Country

France

12. IPD Sharing Statement

Citations:

PubMed Identifier

27399966

Citation

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.

Results Reference

derived

PubMed Identifier

25379192

Citation

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.

Results Reference

derived

PubMed Identifier

23833039

Citation

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.

Results Reference

derived

PubMed Identifier

23144449

Citation

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.

Results Reference

derived

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The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS

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