Pragmatic Clinical Trials in Scleroderma

Not Applicable

• Conditions: Scleroderma, Systemic; Sclerosis, Systemic

• Registration Number: NCT03610217
• Lead Sponsor: University of West London

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-07-25
• Study First Submitted QC: 2018-07-25
• Status Verified: 2018-08
• Study First Posted: 2018-08-01
• Last Update Submitted: 2018-08-02
• Last Update Posted: 2018-08-06
• Study Start: 2018-10
• Primary Completion: 2021-10
• Study Completion: 2021-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 400

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Primary Outcome Measures

Name	Time	Method
Raynaud's phenomenon visual analog scale	3 months	Raynaud's phenomenon visual analog scale variation ranging from 0 to 100 mm (0 no Raynaud's phenomenon, 100 very intense Raynaud's phenomenon)
Time to the development of a new digital ulcer	1 year	Time to the development of a new digital ulcer
Disease activity score 28	3 months	Disease activity score 28 accounting for tender and swollen joints over 28 possible joints. Values \<2.6 remission, values \<3.2 low disease activity, values \>5.1 high disease activity
Constipation visual analog scale	3 months	constipation visual analog scale variation ranging from 0 to 100 mm (0 no constipation, 100 very intense constipation)
Bleeding	1 year	Documentation of bleeding
Time to the healing of a digital ulcer	1 year	Time to the healing of a digital ulcer
Diarrhea visual analog scale	3 months	Diarrhea visual analog scale variation ranging from 0 to 100 mm (0 no diarrhea, 100 very intense diarrhea)
Modified Rodnan skin score	1 year	Modified Rodnan skin score variation. Ranging from a total of 0 (no induration) to 51 (maximum induration)
Forced vital capacity %	1 year	Variation of the forced vital capacity %
GERD-HRQL	3 months	Variation of the Gastro-esophageal reflux disease-health related quality of life questionnaire, ranging from 0 (no symptoms) to 75 (worst symptoms)
Pain visual analog scale	3 months	Pain visual analog scale variation, ranging from 0 to 100 mm (0 no pain, 100 very intense pain)

Trial Locations

Locations (1)

Saint Joseph's Health Care London; 🇨🇦 London, Ontario, Canada