Scleroderma, SystemicPCTSNCT03610217
Pragmatic Clinical Trials in Scleroderma
A study testing Interstitial lung disease induction algorithm, Pulmonary arterial hypertension algorithm and Raynaud's phenomenon algorithm in people with Scleroderma, Systemic and Sclerosis, Systemic, run by University of West London at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Scleroderma, Systemic, Sclerosis, Systemic
- What is being tested?
- Interstitial lung disease induction algorithm, Pulmonary arterial hypertension algorithm and Raynaud's phenomenon algorithm
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- 1 siteCanada
- Study dates
- Oct 2018to Oct 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Refusal to participate or to sign an informed consent form.
Trial locations and contacts
1 site in 1 country.
Canada1 site
Saint Joseph's Health Care London
London, Ontario, n6a 4v2
Janet E Pope, MD, MPH, FRCPSC, 15196466332, Janet.Pope@sjhc.london.on.ca
Andreu Fernandez-Codina, 151964661023, doccodina@gmail.com
About this study
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.
- Conditions
- Scleroderma, Systemic, Sclerosis, Systemic
- Being tested
- Interstitial lung disease induction algorithm, Pulmonary arterial hypertension algorithm, Raynaud's phenomenon algorithm, Digital ulcer algorithm, Inflammatory arthritis algorithm
- Medical subject headings
- Scleroderma, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Interstitial lung disease induction algorithmOther
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.
Pulmonary arterial hypertension algorithmOther
Patients diagnosed with pulmonary arterial hypertension secondary to systemic sclerosis will be randomized to receive anticoagulation (warfarin, rivaroxaban or apixaban)
Raynaud's phenomenon algorithmOther
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.
Digital ulcer algorithmOther
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.
Inflammatory arthritis algorithmOther
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.
Gastroesophageal reflux algorithmOther
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.
Bacterial overgrowth algorithmOther
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.
Constipation algorithmOther
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.
Skin involvement algorithmOther
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.
Pain algorithmOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Interstitial lung disease induction | Experimental | Not described Receives: Other: Interstitial lung disease induction algorithm |
| Pulmonary arterial hypertension | Experimental | Not described Receives: Other: Pulmonary arterial hypertension algorithm |
| Raynaud's phenomenon | Experimental | Not described Receives: Other: Raynaud's phenomenon algorithm |
| Digital ulcers | Experimental | Not described Receives: Other: Digital ulcer algorithm |
| Inflammatory arthritis | Experimental | Not described Receives: Other: Inflammatory arthritis algorithm |
| Gastroesophageal reflux | Experimental | Not described Receives: Other: Gastroesophageal reflux algorithm |
| Bacterial overgrowth | Experimental | Not described Receives: Other: Bacterial overgrowth algorithm |
| Constipation | Experimental | Not described Receives: Other: Constipation algorithm |
| Skin involvement | Experimental | Not described Receives: Other: Skin involvement algorithm |
| Pain | Experimental | Not described Receives: Other: Pain algorithm |
What is being measured
The primary outcome is the main question the study is designed to answer.
Forced vital capacity %
Variation of the forced vital capacity %
Measured: 1 year
Bleeding
Documentation of bleeding
Measured: 1 year
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)
Measured: 3 months
Time to the healing of a digital ulcer
Time to the healing of a digital ulcer
Measured: 1 year
Time to the development of a new digital ulcer
Time to the development of a new digital ulcer
Measured: 1 year
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
Measured: 3 months
GERD-HRQL
Variation of the Gastro-esophageal reflux disease-health related quality of life questionnaire, ranging from 0 (no symptoms) to 75 (worst symptoms)
Measured: 3 months
Diarrhea visual analog scale
Diarrhea visual analog scale variation ranging from 0 to 100 mm (0 no diarrhea, 100 very intense diarrhea)
Measured: 3 months
Constipation visual analog scale
constipation visual analog scale variation ranging from 0 to 100 mm (0 no constipation, 100 very intense constipation)
Measured: 3 months
Modified Rodnan skin score
Modified Rodnan skin score variation. Ranging from a total of 0 (no induration) to 51 (maximum induration)
Measured: 1 year
Pain visual analog scale
Pain visual analog scale variation, ranging from 0 to 100 mm (0 no pain, 100 very intense pain)
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2018
- Study startOct 2018 (estimated)
- Primary completionOct 2021 (estimated)
- Study completionOct 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Scleroderma, SystemicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of West London
- Sponsor type
- University, hospital or other
- Collaborators
- University of Western Ontario, Canada
- Responsible party
- Principal investigator, Andreu Fernandez Codina, University of Western Ontario, Canada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03610217
- Sponsor's protocol ID
- 111419
- Acronym
- PCTS
- Status last verified
- Aug 2018
- First submitted
- 25 Jul 2018
- Last updated
- 6 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 29781586
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pragmatic Clinical Trials in Scleroderma
- ClinicalTrials.gov ID
- NCT03610217
- Acronym / sponsor ID
- PCTS / 111419
- Conditions
- Scleroderma, Systemic, Sclerosis, Systemic
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- University of West LondonUniversity, hospital or other
- Collaborators
- University of Western Ontario, Canada
- Study start
- Oct 2018 (estimated)
- Primary completion
- Oct 2021 (estimated)
- Study completion
- Oct 2021 (estimated)
- First posted
- 1 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| Interstitial lung disease induction | Experimental | Other: Interstitial lung disease induction algorithm |
| Pulmonary arterial hypertension | Experimental | Other: Pulmonary arterial hypertension algorithm |
| Raynaud's phenomenon | Experimental | Other: Raynaud's phenomenon algorithm |
| Digital ulcers | Experimental | Other: Digital ulcer algorithm |
| Inflammatory arthritis | Experimental | Other: Inflammatory arthritis algorithm |
| Gastroesophageal reflux | Experimental | Other: Gastroesophageal reflux algorithm |
| Bacterial overgrowth | Experimental | Other: Bacterial overgrowth algorithm |
| Constipation | Experimental | Other: Constipation algorithm |
| Skin involvement | Experimental | Other: Skin involvement algorithm |
| Pain | Experimental | Other: Pain algorithm |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (1 listed)
- Refusal to participate or to sign an informed consent form.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Interstitial lung disease induction algorithmPatients 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. | Other | Interstitial lung disease induction |
| Pulmonary arterial hypertension algorithmPatients diagnosed with pulmonary arterial hypertension secondary to systemic sclerosis will be randomized to receive anticoagulation (warfarin, rivaroxaban or apixaban) | Other | Pulmonary arterial hypertension |
| Raynaud's phenomenon algorithmPatients 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. | Other | Raynaud's phenomenon |
| Digital ulcer algorithmPatients 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. | Other | Digital ulcers |
| Inflammatory arthritis algorithmPatients 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. | Other | Inflammatory arthritis |
| Gastroesophageal reflux algorithmPatients 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. | Other | Gastroesophageal reflux |
| Bacterial overgrowth algorithmPatients 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. | Other | Bacterial overgrowth |
| Constipation algorithmPatients 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. | Other | Constipation |
| Skin involvement algorithmPatients 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. | Other | Skin involvement |
| Pain algorithmPatients 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. | Other | Pain |
Primary outcome
Forced vital capacity %
Time frame: 1 year
Variation of the forced vital capacity %
Bleeding
Time frame: 1 year
Documentation of bleeding
Raynaud's phenomenon visual analog scale
Time frame: 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 healing of a digital ulcer
Time frame: 1 year
Time to the healing of a digital ulcer
Time to the development of a new digital ulcer
Time frame: 1 year
Time to the development of a new digital ulcer
Disease activity score 28
Time frame: 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
GERD-HRQL
Time frame: 3 months
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
Time frame: 3 months
Diarrhea visual analog scale variation ranging from 0 to 100 mm (0 no diarrhea, 100 very intense diarrhea)
Constipation visual analog scale
Time frame: 3 months
constipation visual analog scale variation ranging from 0 to 100 mm (0 no constipation, 100 very intense constipation)
Modified Rodnan skin score
Time frame: 1 year
Modified Rodnan skin score variation. Ranging from a total of 0 (no induration) to 51 (maximum induration)
Pain visual analog scale
Time frame: 3 months
Pain visual analog scale variation, ranging from 0 to 100 mm (0 no pain, 100 very intense pain)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2018.
- Results publication: PubMed 29781586Fernandez-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.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Scleroderma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Interstitial lung disease induction algorithm, Pulmonary arterial hypertension algorithm and Raynaud's phenomenon algorithm in people with Scleroderma, Systemic and Sclerosis, Systemic, run by University of West London at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Janet E Pope, MD, MPH, FRCPSC (15196466332, Janet.Pope@sjhc.london.on.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Forced vital capacity % (time frame: 1 year). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03610217, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2018.