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Pragmatic Clinical Trials in Scleroderma (PCTS)

Primary Purpose

Scleroderma, Systemic, Sclerosis, Systemic

Status
Unknown status
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Interstitial lung disease induction algorithm
Pulmonary arterial hypertension algorithm
Raynaud's phenomenon algorithm
Digital ulcer algorithm
Inflammatory arthritis algorithm
Gastroesophageal reflux algorithm
Bacterial overgrowth algorithm
Constipation algorithm
Skin involvement algorithm
Pain algorithm
Sponsored by
University of West London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Scleroderma, Systemic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Saint Joseph's Health Care London

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Interstitial lung disease induction

Pulmonary arterial hypertension

Raynaud's phenomenon

Digital ulcers

Inflammatory arthritis

Gastroesophageal reflux

Bacterial overgrowth

Constipation

Skin involvement

Pain

Arm Description

Outcomes

Primary Outcome Measures

Forced vital capacity %
Variation of the forced vital capacity %
Bleeding
Documentation of bleeding
Raynaud's phenomenon visual analog scale
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 healing of a digital ulcer
Time to the healing of a digital ulcer
Time to the development of a new digital ulcer
Time to the development of a new digital ulcer
Disease activity score 28
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
GERD-HRQL
Variation of the Gastro-esophageal reflux disease-health related quality of life questionnaire, ranging from 0 (no symptoms) to 75 (worst symptoms)
Diarrhea visual analog scale
Diarrhea visual analog scale variation ranging from 0 to 100 mm (0 no diarrhea, 100 very intense diarrhea)
Constipation visual analog scale
constipation visual analog scale variation ranging from 0 to 100 mm (0 no constipation, 100 very intense constipation)
Modified Rodnan skin score
Modified Rodnan skin score variation. Ranging from a total of 0 (no induration) to 51 (maximum induration)
Pain visual analog scale
Pain visual analog scale variation, ranging from 0 to 100 mm (0 no pain, 100 very intense pain)

Secondary Outcome Measures

Full Information

First Posted
July 25, 2018
Last Updated
August 2, 2018
Sponsor
University of West London
Collaborators
University of Western Ontario, Canada
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1. Study Identification

Unique Protocol Identification Number
NCT03610217
Brief Title
Pragmatic Clinical Trials in Scleroderma
Acronym
PCTS
Official Title
Pragmatic Clinical Trials in Scleroderma
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Unknown status
Study Start Date
October 2018 (Anticipated)
Primary Completion Date
October 2021 (Anticipated)
Study Completion Date
October 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of West London
Collaborators
University of Western Ontario, Canada

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Scleroderma, Systemic, Sclerosis, Systemic

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
400 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Interstitial lung disease induction
Arm Type
Experimental
Arm Title
Pulmonary arterial hypertension
Arm Type
Experimental
Arm Title
Raynaud's phenomenon
Arm Type
Experimental
Arm Title
Digital ulcers
Arm Type
Experimental
Arm Title
Inflammatory arthritis
Arm Type
Experimental
Arm Title
Gastroesophageal reflux
Arm Type
Experimental
Arm Title
Bacterial overgrowth
Arm Type
Experimental
Arm Title
Constipation
Arm Type
Experimental
Arm Title
Skin involvement
Arm Type
Experimental
Arm Title
Pain
Arm Type
Experimental
Intervention Type
Other
Intervention Name(s)
Interstitial lung disease induction algorithm
Intervention Description
Patients failing first line mycophenolic acid (MFA) will be randomized to MFA plus rituximab or intravenous cyclophosphamide. If they fail the second line they will be crossed over to the other option.
Intervention Type
Other
Intervention Name(s)
Pulmonary arterial hypertension algorithm
Intervention Description
Patients diagnosed with pulmonary arterial hypertension secondary to systemic sclerosis will be randomized to receive anticoagulation (warfarin, rivaroxaban or apixaban)
Intervention Type
Other
Intervention Name(s)
Raynaud's phenomenon algorithm
Intervention Description
Patients with mild Raynaud's phenomenon not responding to the first line treatment (nifedipine), will be randomized to receive losartan or nifedipine plus atorvastatin or nifedipine plus losartan. If they fail the second line they will be crossed over to the other options randomly. Patients with severe Raynaud's phenomenon not responding to the first line treatment (nifedipine) or failing the previous mild Raynaud's algorithm, will be randomized to receive nifedipine plus sildenafil or nifedipine plus intravenous iloprost. If they fail the second line they will be crossed over to the other option.
Intervention Type
Other
Intervention Name(s)
Digital ulcer algorithm
Intervention Description
Patients with active digital ulcers not healing after 3 months or developing new ones with nifedipine will be randomized to nifedipine plus sildenafil or nifedipine plus intravenous iloprost. If they fail the second line they will be crossed over to the other option. Patients who develop new digital ulcers under treatment with nifedipine will be randomized to nifedipine plus atorvastatin plus standard of care or nifedipine plus standard of care. If they fail the second line they will be crossed over to the other option.
Intervention Type
Other
Intervention Name(s)
Inflammatory arthritis algorithm
Intervention Description
Patients with inflammatory arthritis failing methotrexate and/or prednisone and/or hydroxychloroquine and/or sulfasalazine will be randomized to receive intravenous rituximab or subcutaneous tocilizumab. If they fail the second line they will be crossed over to the other option.
Intervention Type
Other
Intervention Name(s)
Gastroesophageal reflux algorithm
Intervention Description
Patients with gastroesophageal reflux failing standard doses of proton pump inhibitors (PPI) will be randomized to receive double doses of PPI or standard dose of PPI plus ranitidine or double doses of PPI plus domperidone or double doses of PPI plus prucalopride/erythromycin. If they fail the second line they will be crossed over to the other options randomly.
Intervention Type
Other
Intervention Name(s)
Bacterial overgrowth algorithm
Intervention Description
Patients with bacterial overgrowth will be randomized to receive erythromycin or metronidazole or amoxicillin. If they fail the second line they will be crossed over to the other options randomly.
Intervention Type
Other
Intervention Name(s)
Constipation algorithm
Intervention Description
Patients with constipation will be randomized to receive bisacodyl or magnesium sulphate or polyethylene glycol or senna.If they fail the second line they will be crossed over to the other options randomly.
Intervention Type
Other
Intervention Name(s)
Skin involvement algorithm
Intervention Description
Patients with skin involvement and modified Rodnan skin score <32 will be randomized to receive methotrexate or mycophenolic acid or methotrexate plus mycophenolic acid. If they fail the second line they will be crossed over to the other option. Patients with skin involvement and modified Rodnan skin score >32 will be randomized to receive methotrexate plus mycophenolic acid or intravenous cyclophosphamide. If they fail the second line they will be crossed over to the other option.
Intervention Type
Other
Intervention Name(s)
Pain algorithm
Intervention Description
Patients with pain failing first line treatment with acetaminophen or celecoxib or ibuprofen will be randomized to receive pregabalin or duloxetine. Patients with skin involvement and modified Rodnan skin score <32 will be randomized to receive methotrexate or mycophenolic acid or methotrexate plus mycophenolic acid. If they fail the second line they will be crossed over to the other option. In case they fail the second line they will be treated with medical marijuana.
Primary Outcome Measure Information:
Title
Forced vital capacity %
Description
Variation of the forced vital capacity %
Time Frame
1 year
Title
Bleeding
Description
Documentation of bleeding
Time Frame
1 year
Title
Raynaud's phenomenon visual analog scale
Description
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 Frame
3 months
Title
Time to the healing of a digital ulcer
Description
Time to the healing of a digital ulcer
Time Frame
1 year
Title
Time to the development of a new digital ulcer
Description
Time to the development of a new digital ulcer
Time Frame
1 year
Title
Disease activity score 28
Description
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
Time Frame
3 months
Title
GERD-HRQL
Description
Variation of the Gastro-esophageal reflux disease-health related quality of life questionnaire, ranging from 0 (no symptoms) to 75 (worst symptoms)
Time Frame
3 months
Title
Diarrhea visual analog scale
Description
Diarrhea visual analog scale variation ranging from 0 to 100 mm (0 no diarrhea, 100 very intense diarrhea)
Time Frame
3 months
Title
Constipation visual analog scale
Description
constipation visual analog scale variation ranging from 0 to 100 mm (0 no constipation, 100 very intense constipation)
Time Frame
3 months
Title
Modified Rodnan skin score
Description
Modified Rodnan skin score variation. Ranging from a total of 0 (no induration) to 51 (maximum induration)
Time Frame
1 year
Title
Pain visual analog scale
Description
Pain visual analog scale variation, ranging from 0 to 100 mm (0 no pain, 100 very intense pain)
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Janet E Pope, MD, MPH, FRCPSC
Phone
15196466332
Email
Janet.Pope@sjhc.london.on.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Andreu Fernandez-Codina, MD, MSc
Phone
151964661023
Email
doccodina@gmail.com
Facility Information:
Facility Name
Saint Joseph's Health Care London
City
London
State/Province
Ontario
ZIP/Postal Code
n6a 4v2
Country
Canada
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Janet E Pope, MD, MPH, FRCPSC
Phone
15196466332
Email
Janet.Pope@sjhc.london.on.ca
First Name & Middle Initial & Last Name & Degree
Andreu Fernandez-Codina
Phone
151964661023
Email
doccodina@gmail.com

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
29781586
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.
Results Reference
result
Links:
URL
https://www.sjhc.london.on.ca/rheumatology
Description
Related Info

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Pragmatic Clinical Trials in Scleroderma

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