Pragmatic Clinical Trials in Scleroderma (PCTS)

University of West London

Status: Unknown

Conditions: Scleroderma, Systemic; Sclerosis, Systemic

Treatments: Other: Constipation algorithm; Other: Gastroesophageal reflux algorithm; Other: Interstitial lung disease induction algorithm; Other: Skin involvement algorithm; Other: Raynaud's phenomenon algorithm; Other: Pain algorithm; Other: Pulmonary arterial hypertension algorithm; Other: Digital ulcer algorithm; Other: Bacterial overgrowth algorithm; Other: Inflammatory arthritis algorithm

Study type: Interventional

Funder types: Other

Identifiers

NCT03610217

111419

Details and patient eligibility

About

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.

Enrollment: 400 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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400 participants in 10 patient groups

Interstitial lung disease induction

Experimental group

Treatment:

Other: Interstitial lung disease induction algorithm

Pulmonary arterial hypertension

Experimental group

Treatment:

Other: Pulmonary arterial hypertension algorithm

Raynaud's phenomenon

Experimental group

Treatment:

Other: Raynaud's phenomenon algorithm

Digital ulcers

Experimental group

Treatment:

Other: Digital ulcer algorithm

Inflammatory arthritis

Experimental group

Treatment:

Other: Inflammatory arthritis algorithm

Gastroesophageal reflux

Experimental group

Treatment:

Other: Gastroesophageal reflux algorithm

Bacterial overgrowth

Experimental group

Treatment:

Other: Bacterial overgrowth algorithm

Constipation

Experimental group

Treatment:

Other: Constipation algorithm

Skin involvement

Experimental group

Treatment:

Other: Skin involvement algorithm

Pain

Experimental group

Treatment:

Other: Pain algorithm