Clinical trial NCT03138941: Validation of the Lupus Low Disease Activity State (LLDAS) in the Asia Pacific Region
Official title: Validation of the Lupus Low Disease Activity State (LLDAS) in the Asia Pacific Region
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Systemic Lupus Erythematosus
Lead sponsor: Monash University
Sponsor class: OTHER
Collaborators: name: Flinders Medical Centre, Adelaide, AUSTRALIA
name: St. Vincent's Hospital, Melbourne, AUSTRALIA
name: Royal Adelaide Hospital, Adelaide, AUSTRALIA
name: University of New South Wales, Sydney, AUSTRALIA
name: People's Hospital, Peking University Health Science Center, Beijing, CHINA
name: Peking University First Hospital, Beijing, CHINA
name: The University of Hong Kong, HONG KONG
name: University of Padjadjaran, Bandung, INDONESIA
name: Tokyo Women's Medical University, JAPAN
name: University of Occupational and Environmental Health, JAPAN
name: Keio University, JAPAN
name: Hanyang University Hospital for Rheumatic Diseases, REPUBLIC OF KOREA
name: University of Santo Tomas Hospital, Philippines
name: National University Hospital, Singapore
name: Tan Tock Seng Hospital
name: Chang Gung Memorial Hospital
name: Taichung Veterans General Hospital
name: Chiang Mai University Hospital, THAILAND
name: Middlemore Hospital, New Zealand
name: North Shore Hospital, Auckland, NEW ZEALAND
name: Auckland District Health Board, Auckland, NEW ZEALAND
name: Teaching Hospital Kandy, SRI LANKA
name: University of the Philippines, Philippines
First posted: 2017-05-03
Enrollment: 5000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult SLE patients with confirmed lupus

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: SLICC-ACR Damage Index
timeFrame: Approximately 5-10 years
Secondary outcomes:
measure: SFv2-36
timeFrame: Approximately 5-10 years
measure: Mortality
timeFrame: Approximately 5-10 years
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Rheumatology Unit, Royal Adelaide Hospital
state: South Australia
city: Adelaide
country: Australia
facility: Department of Rheumatology, Flinders Medical Centre
state: South Australia
city: Clayton
country: Australia
facility: School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing & Health Sciences
state: Victoria
city: Fitzroy
country: Australia
facility: Department of Rheumatology, St Vincent's Hospital (Melbourne)
state: Victoria
city: Beijing
country: China
facility: Department of Rheumatology and Immunology, People's Hospital Peking University Health Science Center
state: Western District
city: Beijing
country: China
facility: Rheumatology and Immunology department, Peking University First Hospital
state: Xicheng District
city: Pok Fu Lam
country: Hong Kong
facility: Division of Rheumatology & Clinical Immunology, Department of Medicine, Queen Mary Hospital, the University of Hong Kong
city: Bandung
country: Indonesia
facility: Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Padjadjaran University/ Hasan Sadikin General Hospital
state: West Java
city: Kitakyushu
country: Japan
facility: The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health
city: Tokyo
country: Japan
facility: Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University
city: Tokyo
country: Japan
facility: Institute of Rheumatology, Tokyo Women's Medical University
city: Seoul
country: Korea, Republic of
facility: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases
city: Manila
country: Philippines
facility: Joint and Bone Center, University of Santo Tomas Hospital
city: Quezon City
country: Philippines
facility: University of the Philippines
city: Singapore
country: Singapore
facility: Rheumatology Division, University Medical Cluster, National University Hospital
city: Tan Tock Seng
country: Singapore
facility: Department of Rheumatology, Allergy & Immunology, Tan Tock Seng Hospital
city: Kandy
country: Sri Lanka
facility: Division of Nephrology, Teaching Hospital Kandy, Sri Lanka
city: Guishan
country: Taiwan
facility: Department of Rheumatology, Allergy and Immunology Chang Gung Memorial Hospital Chang Gung University
state: Taoyuan County
city: Taichung
country: Taiwan
facility: Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital
city: Chiang Mai
country: Thailand
facility: Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University Hospital
state: Muang District
Study officials:
affiliation: Monash University
name: Eric Morand
role: STUDY_CHAIR
References:
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.
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.
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. doi: 10.1186/s13075-016-1163-2.
citation: 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.
citation: 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.
citation: Golder V, Kandane-Rathnayake R, Huq M, Nim HT, Louthrenoo W, Luo SF, Wu YJ, Lateef A, Sockalingam S, Navarra SV, Zamora L, Hamijoyo L, Katsumata Y, Harigai M, Chan M, O'Neill S, Goldblatt F, Lau CS, Li ZG, Hoi A, Nikpour M, Morand EF; Asia-Pacific Lupus Collaboration. Lupus low disease activity state as a treatment endpoint for systemic lupus erythematosus: a prospective validation study. Lancet Rheumatol. 2019 Oct;1(2):e95-e102. doi: 10.1016/S2665-9913(19)30037-2. Epub 2019 Sep 6.
citation: Golder V, Kandane-Rathnayake R, Huq M, Louthrenoo W, Luo SF, Wu YJ, Lateef A, Sockalingam S, Navarra SV, Zamora L, Hamijoyo L, Katsumata Y, Harigai M, Chan M, O'Neill S, Goldblatt F, Lau CS, Li ZG, Hoi A, Nikpour M, Morand EF; Asia Pacific Lupus Collaboration. Evaluation of remission definitions for systemic lupus erythematosus: a prospective cohort study. Lancet Rheumatol. 2019 Oct;1(2):e103-e110. doi: 10.1016/S2665-9913(19)30048-7. Epub 2019 Sep 25.