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Improving the Assessment of SLE Disease Activity

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ClinicalTrials.gov Identifier: NCT03144063
Recruitment Status : Unknown
Verified August 2017 by Zahi Touma, University Health Network, Toronto.
Recruitment status was:  Enrolling by invitation
First Posted : May 8, 2017
Last Update Posted : August 22, 2017
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Zahi Touma, University Health Network, Toronto

Brief Summary:

Physicians' assessment of disease activity in SLE is fundamental but challenging. The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) is one of the most commonly used disease activity indices. Clinical trials experience suggested that the disease activity instruments did not function well on their own, and composite measures were developed to address this issue. This approach has been adopted after learning from clinical trials that the absence of a robust sensitive index is a major flaw when designing a trial. Another issue with clinical trials is the confounding effect of corticosteroids, which to date have been the most effective treatment for the management of lupus. However, unregulated use of corticosteroids in drug trials decrease the investigator's ability to differentiate between the tested drugs and placebo as they appear to enhance response among the placebo arm and thus mask the effect of the tested drug.

In this study, the aim is to develop and validate a new index, SLEDAI-2K Glucocorticosteroid Index (SLEDAI-2KG). It is very challenging to evaluate improvement in drug trials in the context of the standard of care treatment which includes corticosteroids. This novel index, SLEDAI-2KG, will help to overcome the confounding effect of corticosteroids and to allow for more accurate description of disease improvement and thus facilitate accurate investigations of new therapeutic agents.


Condition or disease
Lupus Erythematosus, Systemic SLE

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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Improving the Assessment of Systemic Lupus Erythematosus Disease Activity
Actual Study Start Date : July 11, 2017
Estimated Primary Completion Date : April 2018
Estimated Study Completion Date : June 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lupus

Group/Cohort
Toronto Lupus Cohort

Objective 1 and 3 Cohort:

  • ≥4 American College of Rheumatology (ACR) criteria or 3 ACR criteria plus a typical histological lesion of SLE on renal or skin biopsy
  • Clinician's diagnosis based on his/her assessment
  • Patients from the Toronto Lupus Clinic with regular follow-up, defined as having follow up visits at 3 and 6 months from the baseline visit (1st study visit).
BLISS-52 Cohort

Objective 2 Cohort:

Validation of the SLEDAI-2KG will be completed on BLISS-52 trial data. The extracted trial data consists of data on all patients that participated in the trial.

BLISS-76 Cohort

Objective 2 Cohort:

Validation of the SLEDAI-2KG will be completed on BLISS-76 trial data. The extracted trial data consists of data on all patients that participated in the trial.




Primary Outcome Measures :
  1. Objective I - Initial Development and Validation of Systemic Lupus Erythematosus Disease Activity Index-2000 Glucocorticosteroid (SLEDAI-2KG) [ Time Frame: 3 months ]

    The new index SLEDAI-2KG will be validated against the old index Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) in the TLC cohort. Improved patients (responders) will be identified based on SLEDAI-2K definition of improvement (decrease in the total score by ≥4).

    Clinician scoring on a Likert scale (external construct) for disease activity - Improvement based on predefined definitions


  2. Objective II - Further validation of Systemic Lupus Erythematosus Disease Activity Index-2000 Glucocorticosteroid (SLEDAI-2KG) using BLISS trial data [ Time Frame: 5 months ]
    SLEDAI-2KG will be further validated using BLISS-52 and BLISS-7S trial data on all patients that were enrolled. The primary endpoint in both trials was SLE Responder Index (SRI). The SRI incorporates the Safety of Estrogens in Lupus Erythematosus-National Assessment-SLEDAI (SELENA-SLEDAI), British Isles Lupus Assessment Group (BILAG), and Physician Global Assessment (PGA). The primary outcome of this objective is the SRI-modified: The SRI-modified will include the 2nd and 3rd components of SRI, but replace the SELENA-SLEDAI with the SLEDAI-2KG.

  3. Objective IIIA - Assessment of concurrent construct validity of Systemic Lupus Erythematosus Disease Activity Index-2000 Glucocorticosteroid (SLEDAI-2KG) prospectively in the University of Toronto Lupus Clinic [ Time Frame: 8 months ]
    Improved patients (responders) will be identified based on Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) definition of improvement (decrease in the total score by ≥4).

  4. Objective IIIB - Identification of Systemic Lupus Erythematosus Disease Activity Index-2000 Glucocorticosteroid (SLEDAI-2KG) Responders [ Time Frame: 8 months ]
    SLEDAI-2KG improved patients (responders) will be identified based on the definition of improvement (decrease in the total score by ≥4).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Objective I Initial Development and Validation of SLEDAI-2KG This is a retrospective validation study of SLEDAI-2KG using the University of Toronto Lupus Clinic (TLC) database. Clinical and laboratory data is collected according to a standard protocol at regular intervals (2 to 6 months between visits) and stored on a computer database.

Objective II Further retrospective validation of SLEDAI-2KG using BLISS trial data.

All patients in GSK BLISS-52 (N=865) and BLISS-76 (N=819) were assessed at regular intervals and data including clinical and laboratory features of SLE, medications and in particular corticosteroids was collected and will be used in the validation of SLEDAI-2KG.

Objective III Assessment of concurrent construct validity of SLEDAI-2KG prospectively in the TLC Cohort Patients from the TLC with active disease with a flare (increase in SLEDAI-2K by at least 4) that requires an increase in the dose of prednisone to ≥15 mg/day or initiation of prednisone at ≥15 mg/day.

Criteria

Inclusion Criteria:

Objective I:

  • ≥4 American College of Rheumatology (ACR) criteria or 3 ACR criteria plus a typical histological lesion of SLE on renal or skin biopsy
  • Clinician's diagnosis based on his/her assessment
  • Patients from the Toronto Lupus Clinic with regular follow-up, defined as having follow up visits at 3 and 6 months from the baseline visit (1st study visit).

Objective II:

• Participant in the BLISS-52 and BLISS-76 trials

Objective III:

  • ≥4 American College of Rheumatology (ACR) criteria or 3 ACR criteria plus a typical histological lesion of SLE on renal or skin biopsy
  • Increase in SLEDAI-2K ≥4
  • Clinician's diagnosis based on his/her assessment

Exclusion Criteria:

Objective I and III:

  • Patients with missing follow up visits at 3 and 6 months from the baseline visit (1st study visit).
  • Patients with missing data in the charts for all visits.

Objective II:

• Participants who did not complete the trial and therefore have missing data points for primary endpoint measures


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03144063


Locations
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Canada, Ontario
Toronto Western Hospital
Toronto, Ontario, Canada, M4L2P5
Sponsors and Collaborators
University Health Network, Toronto
GlaxoSmithKline
Investigators
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Principal Investigator: Zahi Touma, MD PhD University Health Network and University of Toronto
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Responsible Party: Zahi Touma, Principal Investigator, University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT03144063    
Other Study ID Numbers: 15-9195
First Posted: May 8, 2017    Key Record Dates
Last Update Posted: August 22, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Zahi Touma, University Health Network, Toronto:
Disease Activity
SLEDAI-2K
Additional relevant MeSH terms:
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Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases