Treatment Outcome in Early Diffuse Cutaneous Systemic Sclerosis (ESOS)

• ClinicalTrials.gov Identifier: NCT02339441
• Recruitment Status: Completed
• First Posted: January 15, 2015
• Last Update Posted: May 13, 2016
• Sponsor: University of Manchester
• Information provided by (Responsible Party): Prof. Ariane herrick, University of Manchester

Tracking Information

• First Submitted Date: December 22, 2014
• First Posted Date: January 15, 2015
• Last Update Posted Date: May 13, 2016
• Study Start Date: June 2010
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 12, 2015): Skin score as measured by modified rodnan skin score [ Time Frame: 24 months ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 15, 2015)

• Pulmonary function as measured by right ventricular systolic pressure (RVSP) or pulmonary artery pressure (PAP) [ Time Frame: 24 months ]
• Echocardiographic findings [ Time Frame: 24 months ]
• Cochin hand function [ Time Frame: 24 months ]
• Fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT) scale [ Time Frame: 24 months ]
• Short form 36 questionnaire (SF-36) [ Time Frame: 24 months ]
• Scleroderma Health Assessment Questionnaire [ Time Frame: 24 months ]
• Haemoglobin [ Time Frame: 24 months ]
• Erythrocyte sedimentation rate [ Time Frame: 24 months ]
• Estimated glomerular filtration rate (eGFR) [ Time Frame: 24 months ]

Original Secondary Outcome Measures (submitted: January 12, 2015)

• Pulmonary function as measured by right ventricular systolic pressure (RVSP) or pulmonary artery pressure (PAP) [ Time Frame: 24 months ]
• Echocardiograhic findings [ Time Frame: 24 months ]
• Cochin hand function [ Time Frame: 24 months ]
• Fatigue as measured by the FACIT fatigue scale [ Time Frame: 24 months ]
• Short form 36 questionnaire (SF-36) [ Time Frame: 24 months ]
• Scleroderma Health Assessment Questionnaire [ Time Frame: 24 months ]
• Haemoglobin [ Time Frame: 24 months ]
• Erythrocyte sedimentation rate [ Time Frame: 24 months ]
• Estimated glomerular filtration rate (eGFR) [ Time Frame: 24 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Treatment Outcome in Early Diffuse Cutaneous Systemic Sclerosis
• Official Title: Treatment Outcome in Early Diffuse Cutaneous Systemic Sclerosis
• Brief Summary: The aim of the study is to compare the effectiveness of commonly used immunosuppressant treatments for early diffuse cutaneous systemic sclerosis (SSc).
• Detailed Description: Diffuse cutaneous systemic sclerosis (SSc) is a rare autoimmune disease characterised by excessive connective tissue in the skin (causing skin thickening called 'scleroderma'), muscle, joints and internal organs. A number of different drugs with effects on the immune system (known as 'immunosuppressants') are currently being used by clinicians in the treatment of early diffuse cutaneous SSc, but all can have significant side effects. We want to know whether any one is definitely effective and, if so, which is the most effective.
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample

Study Population

Eligibility:

Age > 18 Skin thickening < 3 years Immunosuppressant use < 4 months Proximal skin involvement to face/neck, elbow or knee

• Condition: Early Diffuse Cutaneous Systemic Sclerosis

Intervention

• Drug: Methotrexate
  Immunosuppressant agent. Patients treated with Methotrexate at the entry of the study, either oral or subcutaneous with a target dose of 20-25mg weekly.
• Drug: Mycophenolate mofetil
  Immunosuppressant agent. Patients treated with Methotrexate at the entry of the study,recommended dose 500 mg twice daily for 2 weeks increasing to 1gm twice daily.
• Drug: Cyclophosphamide
  Immunosuppressant agent. Patients treated with Methotrexate at the entry of the study, recommend use (i) IV. Minimum monthly dose 500mg/m2 with a recommended duration of 6-12 months. (ii) Oral. 1-2mg/day with a recommended duration of 12 months.

Study Groups/Cohorts

• Methotrexate
  Patients treated with Methotrexate at the entry of the study.
  Intervention: Drug: Methotrexate
• Mycophenolate Mofetil
  Patients treated with Mycophenolate Mofetil at the entry of the study.
  Intervention: Drug: Mycophenolate mofetil
• Cyclophosphamide
  Patients treated with Cyclophosphamide at the entry of the study
  Intervention: Drug: Cyclophosphamide
• No Immunosuppressant
  Patients without immunosuppressant treatment at the entry of the study

Publications *

• Herrick AL, Peytrignet S, Lunt M, Pan X, Hesselstrand R, Mouthon L, Silman AJ, Dinsdale G, Brown E, Czirjak L, Distler JHW, Distler O, Fligelstone K, Gregory WJ, Ochiel R, Vonk MC, Ancuta C, Ong VH, Farge D, Hudson M, Matucci-Cerinic M, Balbir-Gurman A, Midtvedt O, Jobanputra P, Jordan AC, Stevens W, Moinzadeh P, Hall FC, Agard C, Anderson ME, Diot E, Madhok R, Akil M, Buch MH, Chung L, Damjanov NS, Gunawardena H, Lanyon P, Ahmad Y, Chakravarty K, Jacobsen S, MacGregor AJ, McHugh N, Muller-Ladner U, Riemekasten G, Becker M, Roddy J, Carreira PE, Fauchais AL, Hachulla E, Hamilton J, Inanc M, McLaren JS, van Laar JM, Pathare S, Proudman SM, Rudin A, Sahhar J, Coppere B, Serratrice C, Sheeran T, Veale DJ, Grange C, Trad GS, Denton CP. Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study. Ann Rheum Dis. 2018 Apr;77(4):563-570. doi: 10.1136/annrheumdis-2017-211912. Epub 2018 Jan 6.
• Herrick AL, Pan X, Peytrignet S, Lunt M, Hesselstrand R, Mouthon L, Silman A, Brown E, Czirjak L, Distler JHW, Distler O, Fligelstone K, Gregory WJ, Ochiel R, Vonk M, Ancuta C, Ong VH, Farge D, Hudson M, Matucci-Cerinic M, Balbir-Gurman A, Midtvedt O, Jordan AC, Jobanputra P, Stevens W, Moinzadeh P, Hall FC, Agard C, Anderson ME, Diot E, Madhok R, Akil M, Buch MH, Chung L, Damjanov N, Gunawardena H, Lanyon P, Ahmad Y, Chakravarty K, Jacobsen S, MacGregor AJ, McHugh N, Muller-Ladner U, Riemekasten G, Becker M, Roddy J, Carreira PE, Fauchais AL, Hachulla E, Hamilton J, Inanc M, McLaren JS, van Laar JM, Pathare S, Proudman S, Rudin A, Sahhar J, Coppere B, Serratrice C, Sheeran T, Veale DJ, Grange C, Trad GS, Denton CP. Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS). Ann Rheum Dis. 2017 Jul;76(7):1207-1218. doi: 10.1136/annrheumdis-2016-210503. Epub 2017 Feb 10.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 12, 2015): 320
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: March 2016
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Age > 18 Skin thickening < 3 years Immunosuppressant use < 4 months Proximal skin involvement to face/neck, elbow or knee

Exclusion Criteria:

Previous use of more than 4 months of methotrexate, mycophenolate mofetil, cyclophosphamide or other immunosuppressive treatments

Previous use of immunosuppressant therapy other than methotrexate, mycophenolate mofetil or cyclophosphamide within previous months

Previous stem cell transplantation therapy

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT02339441
• Other Study ID Numbers: 10H101429
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Prof. Ariane herrick, University of Manchester
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Manchester
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Ariane Herrick, MD, phD; University of Manchester

• PRS Account: University of Manchester
• Verification Date: May 2016