Ignite Creation Date:
2025-12-24 @ 12:22 PM
Ignite Modification Date:
2026-03-05 @ 11:31 AM
Study NCT ID:
NCT00413361
Status:
COMPLETED
Last Update Posted:
2011-01-27
First Post:
2006-12-18
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D008180', 'term': 'Lupus Erythematosus, Systemic'}], 'ancestors': [{'id': 'D003240', 'term': 'Connective Tissue Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}, {'id': 'D001327', 'term': 'Autoimmune Diseases'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['CARE_PROVIDER', 'INVESTIGATOR']}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 543}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2007-06'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2007-05', 'completionDateStruct': {'date': '2011-01', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2011-01-26', 'studyFirstSubmitDate': '2006-12-18', 'studyFirstSubmitQcDate': '2006-12-18', 'lastUpdatePostDateStruct': {'date': '2011-01-27', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2006-12-19', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2011-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'The number of patient in each group who developed a flare (according to the SELENA-SLEDAI composite criteria) during the study period.', 'timeFrame': '7 months of follow up', 'description': 'The number of patient in each group who developed a flare (according to the SELENA-SLEDAI composite criteria) during the study period.'}], 'secondaryOutcomes': [{'measure': 'The number of patients in each group who developed a flare during the study period.', 'timeFrame': '7 months of follow up', 'description': 'The number of patients in each group who developed a flare during the study period.'}, {'measure': 'The total number of flares in each group', 'timeFrame': '7 months of follow up', 'description': 'The total number of flares in each group'}, {'measure': 'the total dose of steroids in each group', 'timeFrame': '7 months of follow up', 'description': 'the total dose of steroids in each group'}, {'measure': 'the area under the curve of SELENA SLEDAI in each group', 'timeFrame': '7 months of follow up', 'description': 'the area under the curve of SELENA SLEDAI in each group'}, {'measure': 'the mean change of the quality of life questionnaire SF-36', 'timeFrame': '7 months of follow up', 'description': 'the mean change of the quality of life questionnaire SF-36'}, {'measure': 'the mean change on the score of analogical visual scale in each group', 'timeFrame': '7 months of follow up', 'description': 'the mean change on the score of analogical visual scale in each group'}, {'measure': 'Treatment tolerance evaluation will include clinical, electrocardiographic and ophthalmologic screening.', 'timeFrame': '7 months of follow up', 'description': 'Treatment tolerance evaluation will include clinical, electrocardiographic and ophthalmologic screening.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Systemic Lupus Erythematosus', 'Hydroxychloroquine'], 'conditions': ['Systemic Lupus Erythematosus']}, 'referencesModule': {'references': [{'pmid': '27399966', 'type': 'DERIVED', '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.'}, {'pmid': '25379192', 'type': 'DERIVED', '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.'}, {'pmid': '23833039', 'type': 'DERIVED', '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.'}, {'pmid': '23144449', 'type': 'DERIVED', '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.'}]}, 'descriptionModule': {'briefSummary': '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', 'detailedDescription': 'Hydroxychloroquine (HCQ) is a treatment which allows preventing Systemic Lupus Erythematosus (SLE) exacerbations.\n\nHCQ can be measured in whole-blood by HPLC (High Performance Liquid Chromatography).\n\nInterindividual 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.\n\nThe 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\n\nThe secondary objectives are:\n\n* To define biological and clinical hallmarks present at M1 (month 1) which are predictor of SLE exacerbations in the next 6 month,\n* To establish the parameters of HCQ pharmacokinetic model, by a study of population, using a "Bayésienne" approach.\n* To study the influence of allelic variants of drug carriers and other genes in the interindividual variability of blood HCQ concentrations.\n* To study the influence of the compliance in the blood HCQ concentration variability\n* To study the relation between blood HCQ concentrations, SLE activity and quality of life\n* To study the relation between blood HCQ concentrations, SLE activity and lipid profile of the patients\n* To study the relation between ECG abnormalities and blood HCQ concentrations\n* To constitute a bank of serum, a DNAbank, and a RNAbank to permit subsequent studies'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age of 18 and above\n* Diagnosis of Systemic Lupus Erythematosus (SLE) according to the American College of Rheumatology (ACR) Classification Criteria.\n* Treatment with HCQ for at least 6 months, without modification of HCQ dosage for 2 months\n* 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)\n* No increase in the steroids dosage during the 3 previous weeks\n* Steroids dosage lower or equal to 0. 5 mg/kg/day of prednisone equivalent\n* No modifications of a possible immunosuppressor during the 2 previous months\n* SELENA-SLEDAI \\< or = 12\n* Signature of the consent of participation\n\nExclusion Criteria:\n\n* Known retinopathy, present or passed\n* Severe cataract obstructing the ophthalmologic monitoring\n* MONOPHTALM patients\n* Past history of intolerance with HCQ (in particular gastro-intestinal, or retinal) during the possible former use of a higher dosage\n* Use of nivaquine during the 3 previous months\n* Treatment with biotherapy (for example Rituximab) during the 12 previous months\n* Calculated clearance of creatinin lower than 60 ml/min\n* Chronic alcoholism\n* Liver failure\n* Desire of pregnancy in the next 7 months\n* Known non compliance, and risks of random follow-up\n* Absence of social security cover\n\nPeople profiting from a particular protection:\n\n* Pregnant women\n* Age under 18\n* Patient under supervision and TRUSTEESHIP\n* People who are hospitalized without their consent and not protected by the law\n* People who are private of freedom.\n\nCriteria of inclusion at the visit of randomization (D0):\n\nAll the patients responding to the next criterions can be randomized:\n\n* Blood HCQ concentration ranging between 100 and 750 ng/ml at the time of the visit of preselection,\n* No increase in the steroids dosage since last visit\n* No modifications of a possible immunosuppressor since last visit\n* SELENA-SLEDAI \\< or = 12 Activity of the lupus remaining stable (no increase of more than 2 points of the SELENA-SLEDAI),\n* Ophthalmologic examination in the 6 previous months with no contra-indication for the use of HCQ,\n* Absences of conductive disorders on the ECG\n* Use of an effective contraception,\n* Negative Beta-HCG.'}, 'identificationModule': {'nctId': 'NCT00413361', 'briefTitle': 'The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS', 'organization': {'class': 'OTHER', 'fullName': 'Assistance Publique - Hôpitaux de Paris'}, 'officialTitle': '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', 'orgStudyIdInfo': {'id': 'P051070'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'PLACEBO_COMPARATOR', 'label': 'A', 'description': 'placebo', 'interventionNames': ['Drug: versus hydroxychloroquine']}, {'type': 'EXPERIMENTAL', 'label': 'B', 'description': 'versus hydroxychloroquine', 'interventionNames': ['Drug: versus hydroxychloroquine']}], 'interventions': [{'name': 'versus hydroxychloroquine', 'type': 'DRUG', 'description': 'versus hydroxychloroquine', 'armGroupLabels': ['A', 'B']}]}, 'contactsLocationsModule': {'locations': [{'zip': '75013', 'city': 'Paris', 'country': 'France', 'facility': 'Chu Pitie Salpetriere', 'geoPoint': {'lat': 48.85341, 'lon': 2.3488}}, {'zip': '75013', 'city': 'Paris', 'country': 'France', 'facility': 'Hopital la Pitié Salpétrière Assistance Publique', 'geoPoint': {'lat': 48.85341, 'lon': 2.3488}}], 'overallOfficials': [{'name': 'Nathalie COSTEDOAT-CHALUMEAU, MD,', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Assistance Publique - Hôpitaux de Paris'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Assistance Publique - Hôpitaux de Paris', 'class': 'OTHER'}, 'collaborators': [{'name': 'Sanofi-Synthelabo', 'class': 'INDUSTRY'}], 'responsibleParty': {'oldNameTitle': 'Zakia IDIR', 'oldOrganization': 'Department Clinical Rechearch of Developpement'}}}}