Clinical trial NCT03610217: Pragmatic Clinical Trials in Scleroderma
Official title: Pragmatic Clinical Trials in Scleroderma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Scleroderma, Systemic
Sclerosis, Systemic
Lead sponsor: University of West London
Sponsor class: OTHER
Collaborators: name: University of Western Ontario, Canada
First posted: 2018-08-01
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Systemic Sclerosis (SSc) is an autoimmune connective tissue disease characterized by autoantibodies, fibrosis and microvascular injury and endothelial cell activation that results in vascular damage. Vascular injury induces both innate and acquired immune responses resulting in fibroblast activation and organ fibrosis. SSc may target multiple organs, including: skin, lungs, heart, vascularization, kidneys, the gastrointestinal tract and musculoskeletal structures. Mortality among scleroderma patients is significant, with a 3.5 standardized mortality ratio (SMR) in studies of prevalent cases. This mortality may be increased in the early years of the disease, reaching a SMR of 4 in a multinational inception cohort. In general, treatment strategies target involved organs as early as possible to avoid damage. Many treatment options are available for each manifestation, but evidence with respect to the order of treatment is scarce. Financial costs, the lack of proper outcome measures, difficulty to recruit patients as a rare disease, all prevent the development of new big clinical trials, oppositely to other common diseases such as stroke or cancer. The heterogeneous features of SSc may make trials challenging. The current guidelines available are the British guidelines (2017) , and the updated European League Against Rheumatism (EULAR) guidelines, published in 2017. Management guidelines have some gaps regarding second-line treatment, combinations and there are no proposed algorithms.

With the pragmatic trials, the investigators intend to fill the gap between the complicated randomized clinical trials and the observational studies. Using the treatments that have already been proved useful in SSc, in an open-label randomized way and based on some refined expert-made algorithms, will allow the investigators to establish the order in how to use them.

Patients will be offered to participate with the collection of their clinical data and, if they give their consent, they will be randomized according to the algorithms. There will be an optional part of the study consisting in the collection of blood samples and skin samples for future research.


Eligibility criteria: Inclusion Criteria:

* Any patient with an age \>18 years meeting the 2013 SSc classification criteria managed at the Rheumatology division, St. Joseph's Healthcare London.
* Patients who refuse to be randomized for treatments but wish to provide their data for the registry will also be included, after signing the informed consent form.

Exclusion Criteria:

* Refusal to participate or to sign an informed consent form.

Primary outcomes:
measure: Forced vital capacity %
timeFrame: 1 year
measure: Bleeding
timeFrame: 1 year
measure: Raynaud's phenomenon visual analog scale
timeFrame: 3 months
measure: Time to the healing of a digital ulcer
timeFrame: 1 year
measure: Time to the development of a new digital ulcer
timeFrame: 1 year
measure: Disease activity score 28
timeFrame: 3 months
measure: GERD-HRQL
timeFrame: 3 months
measure: Diarrhea visual analog scale
timeFrame: 3 months
measure: Constipation visual analog scale
timeFrame: 3 months
measure: Modified Rodnan skin score
timeFrame: 1 year
measure: Pain visual analog scale
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: London
country: Canada
facility: Saint Joseph's Health Care London
state: Ontario
Study officials:
References:
citation: Fernandez-Codina A, Walker KM, Pope JE; Scleroderma Algorithm Group. Treatment Algorithms for Systemic Sclerosis According to Experts. Arthritis Rheumatol. 2018 Nov;70(11):1820-1828. doi: 10.1002/art.40560. Epub 2018 Sep 17.