SclerodermaCURENCT05168215
Effectiveness of Bosentan Therapy in Patients With Systemic scleRosis and Progressive Digital ulcEr Disease.
An observational study of Scleroderma and Digital Ulcer, run by Elpen Pharmaceutical Co. Inc. at 1 site in Greece.
Trial summary
Digital Ulcers (DEs), are painful open sores on the fingers and toes and are due to limited perfusion of blood vessels in patients with Scleroderma. In particular, ulcers are caused by narrowing of the arteries, resulting in reduced blood supply to the fingers, causing pain and difficult to heal leaving deep scars. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Scleroderma, Digital Ulcer, Autoimmune Diseases
- How many people
- 300 participants
- Where
- 1 siteGreece
- Study dates
- 1 Jan 2022to 1 Jun 2024
- Phase
- Observational
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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adult patients who have been diagnosed with scleroderma (both types:diffuse or limited) and at least one digital ulcer. These patients have been categorised with a total score of ≥ 9 according to 2013 ACR / EULAR Classification Criteria. Regarding current treatment sceme theya are already taking Bosentan (Klimurtan®)
Who may be able to join
- Adult patients
- Patients diagnosed with scleroderma (diffuse or limited)
- Patients with at least one digital ulcer, whether or not it is due to scleroderma
- Patients with 2013 ACR / EULAR Classification Criteria with a total score of ≥ 9
- Patients already taking Bosentan (Klimurtan®)
- Patients who will sign the consent form for their participation in the study
Who cannot join
- Patients with digital ulcers of other etiology, other than scleroderma
- Patients with severe pulmonary arterial hypertension (severe PAH- Category 3-4 according to WHO)
- Patients who do not meet the criteria for taking the study drug, according to the Summary of Product Characteristics
Trial locations and contacts
1 site in 1 country.
Greece1 site, 1 recruiting
- Recruiting
Laikon Hospital of Athens
Athens
P SFIKAKIS, MD, 213 2061 061, psfikakis@med.uoa.gr
About this study
Official title: An Observational Clinical Study to evalUate the Effectiveness of Bosentan Therapy in Patients With Systemic scleRosis and Progressive Digital ulcEr Disease.
Digital Ulcers (DEs), are painful open sores on the fingers and toes and are due to limited perfusion of blood vessels in patients with Scleroderma. In particular, ulcers are caused by narrowing of the arteries, resulting in reduced blood supply to the fingers, causing pain and difficult to heal leaving deep scars. DEs may be present on the rails or fingertips, on the extensor surfaces of the joints, and depending on the underlying calcification. The etiology of ulcers is multifactorial. Raynaud's ischemia, sclerosis, dry skin, calcification and local trauma can all contribute to the onset of Digital Ulcers. Spontaneous fissures or ruptures can also develop into ulcers in patients with scleroderma and severe Raynaud's disease. Whatever the reason for their appearance, DEs negatively affect the quality of life of patients as they complicate even simple daily activities, while they can lead to serious complications such as osteomyelitis or other serious soft tissue infections, up to amputation. Over the last decade, in several randomized clinical trials, DEs have been studied in detail, which are defined or classified differently in each case. The clinical treatment of patients with DE would be facilitated by the availability of specific criteria for the classification of DE. Internationally, the classification of pressure ulcers is usually followed, but this classification is not sufficient for all types of DE observed in Scleroderma. The lack of a clear classification of DEs prompted researchers to evaluate the frequency and morphology of lesions, their characteristics, their physical course, and their healing time in groups of patients with Scleroderma. In a recent study, three categories of classification of digital ulcers based on the patient's clinical picture were proposed by the UK Scleroderma Study Group (UKSSG).
Read the detailed description
- Digital Ulcers: Lesions (on the fingers or peripheral to the metacarpophalangeal joint), with loss of surface epithelialization and visually distinct depth. The ulcer substrate is often superficially liquid with a scaly surface. The damaged skin surrounding the DE is not unusually erythematous and / or impregnated (absence of additional infection). Also, DE often has an overlying crust and patients report severe pain. The most common signs of DE are the fingertips and over the extensor muscle of the (dorsal / back) fold of the hands in relation to subcutaneous calcification. Less commonly, DEs may occur in other places on the hands, such as above the lateral folds of the fingers and at the base of the nail.
- Healed Ulcer: Damage with complete surface epithelialization (in any other case it will be classified as DE).
- No Ulcer: Any lesions that do not meet the definitions of either DEs or healed DEs, including (not only) phalangeal pitting scars, hyperkeratosis and fissures.
In general, targeted future research is needed to improve the reliability of the clinical evaluation of Finger Ulcers for their treatment and to optimize the quality of life of patients.
Systemic Sclerosis Criteria (Scleroderma) In 1980, the American College of Rheumatology (ACR), in conjunction with the European League Against Rheumatism (EULAR), defined the classification criteria for Systemic Sclerosis / Scleroderma. Due to the lack of sensitivity in locating the early stages of Scleroderma and especially the limited cutaneous Systemic Scleroderma, the classification criteria were revised in 2013. It has been found that the thickening of the skin of the fingers that extends near the metacarpophalangeal joints is sufficient to classify the patient with Scleroderma, if this is not obvious, seven additional elements apply, each with a different severity. Specifically, the data are: thickening of the skin of the fingers, finger lesions, teleangiectasia, abnormal capillaries, interstitial pneumonia or Pulmonary Arterial Hypertension, Raynaud's phenomenon and autoantibodies associated with All cases of patients with Scleroderma according to the ACR criteria of 1980 were also classified with Scleroderma and the new criteria of 2013, where several additional cases of patients with Systemic Sclerosis were added.
- Conditions
- Scleroderma, Digital Ulcer, Autoimmune Diseases, Diffuse Cutaneous Systemic Sclerosis, Reynold Syndrome
- Medical subject headings
- Scleroderma, Diffuse, digital ulcers, Autoimmune Diseases
What is being measured
The primary outcome is the main question the study is designed to answer.
Digital Ulcers
The change in the number of finger ulcers and the appearance or not of new ones.
Measured: 0-18 months
Secondary outcomes (4)
Modified Rodnan Skin Score (ΜRSS)
The change in the rating on the modified Rodnan leather scale
Measured: 18 months
Raynaud's Condition Score RCS
The change in the rating on the Raynaud scale
Measured: 0-18 months
EUSTAR activity index
The change in the score on the EUSTAR activity scale
Measured: 0-18 months
Adverse Events, AE
Number of Adverse Events during the study period
Measured: 0-18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2021
- Study start1 Jan 2022
- Primary completion1 Jun 2024 (estimated)
- Study completion1 Jun 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for SclerodermaStudies 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
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Elpen Pharmaceutical Co. Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05168215
- Sponsor's protocol ID
- 2020-BSN-EL-128
- Acronym
- CURE
- Status last verified
- Oct 2023
- First submitted
- 9 Dec 2021
- Last updated
- 1 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Makela M, Heliovaara M, Sievers K, Knekt P, Maatela J, Aromaa A. Musculoskeletal disorders as determinants of disability in Finns aged 30 years or more. J Clin Epidemiol. 1993 Jun;46(6):549-59. doi: 10.1016/0895-4356(93)90128-n.
PubMed 8501482J. H. Kellgren, J. S. Lawrence, and Jean Aitken-Swan, Rheumatic complaints in an urban population, From the Walkden Miners' Clinic and the Departments of Rheumatism Research and Occupational Health, University of Manchester (January 24, 1953).
Vivino FB. Sjogren's syndrome: Clinical aspects. Clin Immunol. 2017 Sep;182:48-54. doi: 10.1016/j.clim.2017.04.005. Epub 2017 Apr 17.
PubMed 28428095P.Vlachogiannopoulos, H.M. Moutsopoulos, Systemic Sclerosis (Scleroderma), Orphanet Encyclopedia, November 2001.
van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, Matucci-Cerinic M, Naden RP, Medsger TA Jr, Carreira PE, Riemekasten G, Clements PJ, Denton CP, Distler O, Allanore Y, Furst DE, Gabrielli A, Mayes MD, van Laar JM, Seibold JR, Czirjak L, Steen VD, Inanc M, Kowal-Bielecka O, Muller-Ladner U, Valentini G, Veale DJ, Vonk MC, Walker UA, Chung L, Collier DH, Csuka ME, Fessler BJ, Guiducci S, Herrick A, Hsu VM, Jimenez S, Kahaleh B, Merkel PA, Sierakowski S, Silver RM, Simms RW, Varga J, Pope JE. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum. 2013 Nov;65(11):2737-47. doi: 10.1002/art.38098. Epub 2013 Oct 3.
PubMed 24122180Steen V, Denton CP, Pope JE, Matucci-Cerinic M. Digital ulcers: overt vascular disease in systemic sclerosis. Rheumatology (Oxford). 2009 Jun;48 Suppl 3:iii19-24. doi: 10.1093/rheumatology/kep105.
PubMed 19487218Tsifetaki N, Georgiadis AN, Alamanos Y, Fanis S, Argyropoulou MI, Drosos AA. Subclinical atherosclerosis in scleroderma patients. Scand J Rheumatol. 2010 Aug;39(4):326-9. doi: 10.3109/03009741003605648.
PubMed 20476856Guiducci S, Giacomelli R, Cerinic MM. Vascular complications of scleroderma. Autoimmun Rev. 2007 Sep;6(8):520-3. doi: 10.1016/j.autrev.2006.12.006. Epub 2007 Jan 12.
PubMed 17854742EMA, Guideline on the clinical investigations of medicinal products for the treatment of pulmonary arterial hypertension, November 2008.
Korn JH, Mayes M, Matucci Cerinic M, Rainisio M, Pope J, Hachulla E, Rich E, Carpentier P, Molitor J, Seibold JR, Hsu V, Guillevin L, Chatterjee S, Peter HH, Coppock J, Herrick A, Merkel PA, Simms R, Denton CP, Furst D, Nguyen N, Gaitonde M, Black C. Digital ulcers in systemic sclerosis: prevention by treatment with bosentan, an oral endothelin receptor antagonist. Arthritis Rheum. 2004 Dec;50(12):3985-93. doi: 10.1002/art.20676.
PubMed 15593188Amanzi L, Braschi F, Fiori G, Galluccio F, Miniati I, Guiducci S, Conforti ML, Kaloudi O, Nacci F, Sacu O, Candelieri A, Pignone A, Rasero L, Conforti D, Matucci-Cerinic M. Digital ulcers in scleroderma: staging, characteristics and sub-setting through observation of 1614 digital lesions. Rheumatology (Oxford). 2010 Jul;49(7):1374-82. doi: 10.1093/rheumatology/keq097. Epub 2010 Apr 16.
PubMed 20400463Romanelli, M., Clark, M., Cherry, G.W., Colin, D., Defloor, T. (Eds.), © 2006 Science and Practice of Pressure Ulcer Management.
Hughes M, Tracey A, Bhushan M, Chakravarty K, Denton CP, Dubey S, Guiducci S, Muir L, Ong V, Parker L, Pauling JD, Prabu A, Rogers C, Roberts C, Herrick AL. Reliability of digital ulcer definitions as proposed by the UK Scleroderma Study Group: A challenge for clinical trial design. J Scleroderma Relat Disord. 2018 Jun 1;3(2):170-174. doi: 10.1177/2397198318764796. Epub 2018 Mar 27.
PubMed 29876526ACR/EULAR Classification Criteria for Systemic Sclerosis (SSc, Scleroderma), https://www.rheumatology.org/Portals/0/Files/SSc%20Class%20Criteria%20slides.pdf.
. Sakkas L. & Vaiopoulos G. The new 2013 ACR/EULAR classification criteria for systemic sclerosis pave the way for treatment in pre-scleroderma patients. 21;1;2015