Improving the Assessment of SLE Disease Activity

March 24, 2025 updated by: Zahi Touma, University Health Network, Toronto

Improving the Assessment of Systemic Lupus Erythematosus Disease Activity

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

Objectives:

  1. To describe the development and initial validation of the SLEDAI-2KG using the Toronto Lupus Cohort (TLC) database.
  2. To conduct further validation of SLEDAI-2KG using BLISS trial data.
  3. To assess concurrent construct validity of SLEDAI-2KG prospectively in the University of Toronto Lupus Clinic.

Study design:

  1. Objective one is a single center study aiming to derive a new index, SLEDAI-2KG, based on SLEDAI-2K. Scoring of SLEDAI-2KG will be determined in this study.
  2. Objective two is a retrospective analysis conducted on prospectively collected data from two clinical trials, BLISS-52 and BLISS-76.
  3. Objective three is a single centre prospective study.

Study Population and Sampling Methods:

Objective I patient selection: Patients with active disease, SLEDAI-2K ≥0, will be identified in the TLC database. All patients must have follow up visits at 3 and 6 months.

Objective II: Data from BLISS-52 and BLISS-76 trials will be used. Objective III patient selection: Patients followed at the Toronto Lupus Clinic from May 2017 to December 2017. Patients will be identified based on active disease with a flare (increase in SLEDAI-2K by at least 4 requiring an increase in the dose of prednisone to ≥ 15 mg/day or initiation of prednisone at ≥ 15 mg/day).

Objective III patient selection: Patients followed at the Toronto Lupus Clinic from May 2017 to December 2017. The investigator will identify patients with active disease with a flare (increase in SLEDAI-2K by at least 4 requiring an increase in the dose of prednisone to ≥ 15 mg/day or initiation of prednisone at ≥ 15 mg/day).

Data Sources:

The University of Toronto Lupus Cohort dataset and GSK BLISS-52 and BLISS-76 trial data The Toronto Lupus Cohort (TLC) is the largest lupus cohort in Canada, and more than 1600 patients have been enrolled in this cohort. Patients in the TLC are seen at regular intervals (2-6 months apart) and data, including laboratory and clinical parameters important to lupus, is collected using a well-defined protocol.

Data Analysis Methods:

In objective I - Phase 1 will focus on the identification of scenarios of real patients to derive weight scores for Glucocorticosteroid (GCS). Phase 2 will focus on the development of SLEDAI-2KG (derivation of an equation to explain the link between SLEDAI-2K and GCS doses) and phase 3 focused on SLEDAI-2KG validation.

The analysis of the initial validation of SLEDAI-2KG will be conducted on the selected patients from the TLC. Improved patients (responders) will be identified based on SLEDAI-2K definition of improvement and further will be studied by calculating the SLEDAI-2KG using the above described models. The mean change of SLEDAI-2K scores and the mean change of SLEDAI-2KG scores in the responders will be studied. Using the SLEDAI-2K responders as "Gold Standard", it will be determined if SLEDAI-2KG responders are true responders and not false responders.

Concurrent construct validity: A clinician (external construct) who does not know the patients and will evaluate each patient's record (electronic record and medical chart) and assign a clinical activity score for each assessment according to the following scale: improved, same, and worse, using standardized predefined definitions. The correlation between the external construct and the change in SLEDAI-2K and SLEDAI-2KG scores will be studied. Using the clinician scoring of disease activity-Improved as "Gold Standard", the results of SLEDAI-2K and SLEDAI-2KG responders will be analyzed by constructing two 2x2 tables.

Sample Size for 3 objectives:

Sample Size 1: The sample size calculation of needed scenarios was based on the assumption of reliability (Intra-class Correlation Coefficient (ICC)) ≥ 0.80 with a standard error of 0.05 and 3 raters. The required minimum was 46 scenarios.

Sample Size 2: For objective two all data available from the BLISS-52 and BLISS-76 trials will be used.

Sample Size 3: For objective three the investigator's target sample size is 100 patients and to achieve this number at least 18 months will be required and subsequently a 6 months period for follow-up for each patients. Based on the COSMIN recommendations, a sample size ≥100 is recommended in this step

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
247

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M4L2P5
        • Toronto Western Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
3 months
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.
5 months
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).
8 months
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).
8 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Health Network, Toronto

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
GlaxoSmithKline

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Zahi Touma, MD PhD, University Health Network and University of Toronto

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 11, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 4, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 4, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 28, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 3, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 8, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 28, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 24, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 15-9195

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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