Validation of the Lupus Low Disease Activity State (LLDAS) in the Asia Pacific Region

Systemic Lupus Erythematosus Clinical Trial

— APLCLLDAS  

Official title:

Validation of the Lupus Low Disease Activity State (LLDAS) in the Asia Pacific Region

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03138941
• Other study ID #: APLC LLDAS Study
• Status: Recruiting
• Start date: September 1, 2013
• Est. completion date: December 31, 2032

Study information

• Verified date: May 2022
• Source: Monash University
• Contact: Eric F Morand
• Phone: + 61 3 8572 2650
• Email: eric.morand[@]monash.edu
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Lupus Low Disease Activity State (LLDAS) study is an international, multi-centre prospective study, developed by the Asia Pacific Lupus Collaboration (APLC) to investigate whether the attainment of LLDAS is associated with improved outcomes in patients with Systemic Lupus Erythematosus (SLE).

SLE, or lupus, is the archetypal multisystem autoimmune disease, with an estimated incidence of 5-50 cases per 100,000 people. Patients with SLE, usually young women, suffer a marked loss of life expectancy, and severe morbidity, due to a heterogeneous range of clinical manifestations caused by autoimmune-mediated inflammation of multiple organs. The most severe manifestations of SLE are the accrual of irreversible organ damage, especially renal and central nervous system (CNS) involvement. As there is no effective targeted monotherapy for SLE, patients also suffer severe toxicity from the use of glucocorticoids and broad-spectrum immunosuppressive therapies. Despite combination therapy with current drugs, many studies show that the majority of patients suffer inadequate disease control and inexorably accrue permanent organ damage over time.

The diversity of clinical features of active SLE has made quantification of disease activity problematic. Although there are a number of published systems in use to measure SLE disease activity, there are widely acknowledged problems with these instruments. Published definitions of remission are so stringent that they are met by less than 5% of patients. This lead to the realisation that rather than lupus remission, a lupus low disease activity state target may be more feasible, and that patients with low disease activity are more homogeneous than patients with active disease. Thus, the development of a definition of lupus low disease activity, which is feasible and has face validity, escapes the complexity of attempts to quantify heterogeneous states of active disease.

In this study, the investigators will prospectively collect longitudinal data on consecutive SLE patients at each centre to evaluate the LLDAS definition. Protection from organ damage accrual as the primary endpoint.

Description:

In this study, patients with SLE will be followed for ~ 5 years. Regular recordings of the data needed to score LLDAS (disease activity and treatment domains, see Franklyn L et al, Ann Rheum Dis 2016) will be collected, as well as annual recording of lupus-related damage using the SLICC_ACR Damage Index (SDI) and quality of life using the Short Form 36 version 2 (SF36v2).

At conclusion of primary data collection, the associate of LLDAS attainment, or sustained attainment, with protection from organ damage accrual will be ascertained.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5000
• Est. completion date: December 31, 2032
• Est. primary completion date: December 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• All patients have to meet either the 1997 American College of Rheumatology (ACR) Modified Classification Criteria for SLE, with at least four of the 11 items; or alternatively, fulfil the Systemic Lupus International Collaborating Clinics (SLICC) 2012 Classification Criteria, with at least four of the 17 items (at least one clinical and one immunological criterion) or with lupus nephritis in the presence of at least one immunological criteria. Patients can be either newly diagnosed or longstanding lupus patients.

All patients must be over the age of 18 and competent to provide written consent.

Exclusion Criteria:

• Patients less than 18 years of age and patients who are unable to consent are excluded from the study.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Locations

Country	Name	City	State
Australia	Department of Rheumatology, Flinders Medical Centre	Adelaide	South Australia
Australia	Rheumatology Unit, Royal Adelaide Hospital	Adelaide	South Australia
Australia	School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing & Health Sciences	Clayton	Victoria
Australia	Department of Rheumatology, St Vincent's Hospital (Melbourne)	Fitzroy	Victoria
China	Department of Rheumatology and Immunology, People's Hospital Peking University Health Science Center	Beijing	Western District
China	Rheumatology and Immunology department, Peking University First Hospital	Beijing	Xicheng District
Hong Kong	Division of Rheumatology & Clinical Immunology, Department of Medicine, Queen Mary Hospital, the University of Hong Kong	Pok Fu Lam
Indonesia	Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Padjadjaran University/ Hasan Sadikin General Hospital	Bandung	West Java
Japan	The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health	Kitakyushu
Japan	Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University	Tokyo
Japan	Institute of Rheumatology, Tokyo Women's Medical University	Tokyo
Korea, Republic of	Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases	Seoul
Philippines	Joint and Bone Center, University of Santo Tomas Hospital	Manila
Philippines	University of the Philippines	Quezon City
Singapore	Rheumatology Division, University Medical Cluster, National University Hospital	Singapore
Singapore	Department of Rheumatology, Allergy & Immunology, Tan Tock Seng Hospital	Tan Tock Seng
Sri Lanka	Division of Nephrology, Teaching Hospital Kandy, Sri Lanka	Kandy
Taiwan	Department of Rheumatology, Allergy and Immunology Chang Gung Memorial Hospital Chang Gung University	Guishan	Taoyuan County
Taiwan	Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital	Taichung
Thailand	Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University Hospital	Chiang Mai	Muang District

Sponsors (24)

Lead Sponsor

Collaborator

Monash University

Auckland District Health Board, Auckland, NEW ZEALAND, Chang Gung Memorial Hospital, Chiang Mai University Hospital, THAILAND, Flinders Medical Centre, Adelaide, AUSTRALIA, Hanyang University Hospital for Rheumatic Diseases, REPUBLIC OF KOREA, Keio University, JAPAN, Middlemore Hospital, New Zealand, National University Hospital, Singapore, North Shore Hospital, Auckland, NEW ZEALAND, Peking University First Hospital, Beijing, CHINA, People's Hospital, Peking University Health Science Center, Beijing, CHINA, Royal Adelaide Hospital, Adelaide, AUSTRALIA, St. Vincent's Hospital, Melbourne, AUSTRALIA, Taichung Veterans General Hospital, Tan Tock Seng Hospital, Teaching Hospital Kandy, SRI LANKA, The University of Hong Kong, HONG KONG, Tokyo Women's Medical University, JAPAN, University of New South Wales, Sydney, AUSTRALIA, University of Occupational and Environmental Health, JAPAN, University of Padjadjaran, Bandung, INDONESIA, University of Santo Tomas Hospital, Philippines, University of the Philippines, Philippines

Countries where clinical trial is conducted

Australia,  China,  Hong Kong,  Indonesia,  Japan,  Korea, Republic of,  Philippines,  Singapore,  Sri Lanka,  Taiwan,  Thailand, 

References & Publications (7)

Franklyn K, Lau CS, Navarra SV, Louthrenoo W, Lateef A, Hamijoyo L, Wahono CS, Chen SL, Jin O, Morton S, Hoi A, Huq M, Nikpour M, Morand EF; Asia-Pacific Lupus Collaboration. Definition and initial validation of a Lupus Low Disease Activity State (LLDAS). Ann Rheum Dis. 2016 Sep;75(9):1615-21. doi: 10.1136/annrheumdis-2015-207726. Epub 2015 Oct 12. — View Citation

Golder V, Huq M, Franklyn K, Calderone A, Lateef A, Lau CS, Lee ALH, Navarra STV, Godfrey T, Oon S, Hoi AYB, Morand EF, Nikpour M. Does expert opinion match the operational definition of the Lupus Low Disease Activity State (LLDAS)? A case-based construct validity study. Semin Arthritis Rheum. 2017 Jun;46(6):798-803. doi: 10.1016/j.semarthrit.2017.01.007. Epub 2017 Jan 18. — View Citation

Golder V, Kandane-Rathnayake R, Hoi AY, Huq M, Louthrenoo W, An Y, Li ZG, Luo SF, Sockalingam S, Lau CS, Lee AL, Mok MY, Lateef A, Franklyn K, Morton S, Navarra ST, Zamora L, Wu YJ, Hamijoyo L, Chan M, O'Neill S, Goldblatt F, Morand EF, Nikpour M; Asia-Pacific Lupus Collaboration. Frequency and predictors of the lupus low disease activity state in a multi-national and multi-ethnic cohort. Arthritis Res Ther. 2016 Nov 9;18(1):260. — View Citation

Golder V, Kandane-Rathnayake R, Hoi AY, Huq M, Louthrenoo W, An Y, Li ZG, Luo SF, Sockalingam S, Lau CS, Mok MY, Lateef A, Franklyn K, Morton S, Navarra ST, Zamora L, Wu YJ, Hamijoyo L, Chan M, O'Neill S, Goldblatt F, Nikpour M, Morand EF; Asia-Pacific Lupus Collaboration. Association of the lupus low disease activity state (LLDAS) with health-related quality of life in a multinational prospective study. Arthritis Res Ther. 2017 Mar 20;19(1):62. doi: 10.1186/s13075-017-1256-6. — View Citation

Golder V., Kandane-Rathnayake R., Huq M., Louthrenoo W., Luo S.F., Jan Wu Y.J., Lateef A., Sockalingam S., Navarra S.T. V., Zamora L., Hamijoyo L., Katsumata Y., Harigai M., Chan M., O'Neill S., Goldblatt F., Lau, C.S., Li Z.G., Hoi A, Nikpour M., Morand E. Evaluation of remission definitions for systemic lupus erythematosus: a prospective cohort study. The Lancet Rheumatology. Oct 2019, Vol.1 Issue 2.

Golder V., Kandane-Rathnayake R., Huq M., Nim H.T., Louthrenoo W., Luo S.F., Jan Wu Y.J., Lateef A., Sockalingam S., Navarra S.T. V., Zamora L., Hamijoyo L., Katsumata Y., Harigai M., Chan M., O'Neill S., Goldblatt F., Lau, C.S., Li Z.G., Hoi A, Nikpour M., Morand E., 6 Sep 2019, Lupus low disease activity state as a treatment endpoint for systemic lupus erythematosus: a prospective validation study. The Lancet Rheumatology. Vol.1 Issue 2.

Kandane-Rathnayake R, Golder V, Louthrenoo W, Luo SF, Jan Wu YJ, Li Z, An Y, Lateef A, Sockalingam S, Navarra SV, Zamora L, Hamijoyo L, Katsumata Y, Harigai M, Chan M, O'Neill S, Goldblatt F, Hao Y, Zhang Z, Al-Saleh J, Khamashta M, Takeuchi T, Tanaka Y, Bae SC, Lau CS, Hoi A, Nikpour M, Morand EF. Development of the Asia Pacific Lupus Collaboration cohort. Int J Rheum Dis. 2019 Mar;22(3):425-433. doi: 10.1111/1756-185X.13431. Epub 2018 Nov 5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SLICC-ACR Damage Index	Organ damage accrual	Approximately 5-10 years
Secondary	SFv2-36	Quality of Life	Approximately 5-10 years
Secondary	Mortality	Mortality	Approximately 5-10 years

External Links

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