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Pragmatic Clinical Trials in Scleroderma

Not Applicable
Conditions
Scleroderma, Systemic
Sclerosis, Systemic
Interventions
Other: Pulmonary arterial hypertension algorithm
Other: Pain algorithm
Other: Inflammatory arthritis algorithm
Other: Digital ulcer algorithm
Other: Gastroesophageal reflux algorithm
Other: Interstitial lung disease induction algorithm
Other: Constipation algorithm
Other: Raynaud's phenomenon algorithm
Other: Bacterial overgrowth algorithm
Other: Skin involvement algorithm
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

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
Arm && Interventions
GroupInterventionDescription
Pulmonary arterial hypertensionPulmonary arterial hypertension algorithm-
PainPain algorithm-
Inflammatory arthritisInflammatory arthritis algorithm-
Digital ulcersDigital ulcer algorithm-
Gastroesophageal refluxGastroesophageal reflux algorithm-
Interstitial lung disease inductionInterstitial lung disease induction algorithm-
ConstipationConstipation algorithm-
Raynaud's phenomenonRaynaud's phenomenon algorithm-
Bacterial overgrowthBacterial overgrowth algorithm-
Skin involvementSkin involvement algorithm-
Primary Outcome Measures
NameTimeMethod
Diarrhea visual analog scale3 months

Diarrhea visual analog scale variation ranging from 0 to 100 mm (0 no diarrhea, 100 very intense diarrhea)

Modified Rodnan skin score1 year

Modified Rodnan skin score variation. Ranging from a total of 0 (no induration) to 51 (maximum induration)

Raynaud's phenomenon visual analog scale3 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 ulcer1 year

Time to the development of a new digital ulcer

Disease activity score 283 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

Forced vital capacity %1 year

Variation of the forced vital capacity %

GERD-HRQL3 months

Variation of the Gastro-esophageal reflux disease-health related quality of life questionnaire, ranging from 0 (no symptoms) to 75 (worst symptoms)

Constipation visual analog scale3 months

constipation visual analog scale variation ranging from 0 to 100 mm (0 no constipation, 100 very intense constipation)

Pain visual analog scale3 months

Pain visual analog scale variation, ranging from 0 to 100 mm (0 no pain, 100 very intense pain)

Bleeding1 year

Documentation of bleeding

Time to the healing of a digital ulcer1 year

Time to the healing of a digital ulcer

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Saint Joseph's Health Care London

🇨🇦

London, Ontario, Canada

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