Systemic Lupus ErythematosusPhase 4NCT00413361
The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS
A Phase 4 study testing versus hydroxychloroquine in people with Systemic Lupus Erythematosus, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.
Trial 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 more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Systemic Lupus Erythematosus
- What is being tested?
- versus hydroxychloroquine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 543 participants
- Where
- 2 sitesFrance
- Study dates
- Jun 2007to Jan 2011
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- No modifications of a possible immunosuppressor during the 2 previous months
- SELENA-SLEDAI < or = 12
- Signature of the consent of participation
Who cannot join
- 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
Show all 28Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
France2 sites
Chu Pitie Salpetriere
Paris, 75013
Hopital la Pitié Salpétrière Assistance Publique
Paris, 75013
About this study
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
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
- Systemic Lupus Erythematosus
- Being tested
- versus hydroxychloroquine
- Keywords
- Systemic Lupus Erythematosus, Hydroxychloroquine
- Medical subject headings
- Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
versus hydroxychloroquineDrug
versus hydroxychloroquine
| Study group | Role | What they receive |
|---|---|---|
| A | Placebo comparator | placebo Receives: Drug: versus hydroxychloroquine |
| B | Experimental | versus hydroxychloroquine Receives: Drug: versus hydroxychloroquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 7 months of follow up
Secondary outcomes (7)
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.
Measured: 7 months of follow up
The total number of flares in each group
The total number of flares in each group
Measured: 7 months of follow up
the total dose of steroids in each group
the total dose of steroids in each group
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 7 months of follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2006 (estimated)
- Study startJun 2007
- Primary completionJan 2011
- Study completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Systemic Lupus ErythematosusStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Care provider, Investigator
- Enrolment
- 543 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi-Synthelabo
- Investigators
- Nathalie COSTEDOAT-CHALUMEAU, MD,, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00413361
- Sponsor's protocol ID
- P051070
- Status last verified
- May 2007
- First submitted
- 18 Dec 2006
- Last updated
- 27 Jan 2011
- Results posted
- No
- Data monitoring committee
- Yes
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 27399966Schoindre 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 25379192Morel 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 23833039Costedoat-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
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00413361
- Acronym / sponsor ID
- P051070
- Conditions
- Systemic Lupus Erythematosus
- Keywords
- Systemic Lupus Erythematosus, Hydroxychloroquine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 543 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Sanofi-Synthelabo
- Study start
- Jun 2007
- Primary completion
- Jan 2011 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 19 Dec 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Placebo comparator | Drug: versus hydroxychloroquineplacebo |
| B | Experimental | Drug: versus hydroxychloroquineversus hydroxychloroquine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (28 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| versus hydroxychloroquineversus hydroxychloroquine | Drug | A, B |
Primary outcome
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
The number of patient in each group who developed a flare (according to the SELENA-SLEDAI composite criteria) during the study period.
7 secondary outcomes
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
Time frame: 7 months of follow up
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
Time frame: 7 months of follow up
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
Time frame: 7 months of follow up
Treatment tolerance evaluation will include clinical, electrocardiographic and ophthalmologic screening.
Time frame: 7 months of follow up
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2011.
- Derived from this study: PubMed 27399966Morris 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.
- Derived from this study: PubMed 25379192Schoindre 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.
- Derived from this study: PubMed 23833039Morel 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.
- Derived from this study: PubMed 23144449Costedoat-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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nathalie COSTEDOAT-CHALUMEAU, MD, principal investigator
Assistance Publique - Hôpitaux de Paris
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing versus hydroxychloroquine in people with Systemic Lupus Erythematosus, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00413361, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2011.