Effectiveness of Bosentan Therapy in Patients With Systemic scleRosis and Progressive Digital ulcEr Disease.

Autoimmune Diseases Clinical Trial

— CURE  

Official title:

An Observational Clinical Study to evalUate the Effectiveness of Bosentan Therapy in Patients With Systemic scleRosis and Progressive Digital ulcEr Disease.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05168215
• Other study ID #: 2020-BSN-EL-128
• Status: Recruiting
• Start date: January 1, 2022
• Est. completion date: June 1, 2024

Study information

• Verified date: October 2023
• Source: Elpen Pharmaceutical Co. Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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).

Description:

1. 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. 2. Healed Ulcer: Damage with complete surface epithelialization (in any other case it will be classified as DE). 3. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: June 1, 2024
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Autoimmune Diseases
• Diffuse Cutaneous Systemic Sclerosis
• Digital Ulcer
• Scleroderma
• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Skin Ulcer
• Ulcer

Locations

Country	Name	City	State
Greece	Laikon Hospital of Athens	Athens

Sponsors (1)

Lead Sponsor	Collaborator
Elpen Pharmaceutical Co. Inc.

Country where clinical trial is conducted

Greece, 

References & Publications (21)

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ACR/EULAR Classification Criteria for Systemic Sclerosis (SSc, Scleroderma), https://www.rheumatology.org/Portals/0/Files/SSc%20Class%20Criteria%20slides.pdf.

Amanzi 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. — View Citation

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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. — View Citation

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Romanelli, M., Clark, M., Cherry, G.W., Colin, D., Defloor, T. (Eds.), © 2006 Science and Practice of Pressure Ulcer Management.

Steen 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. — View Citation

Tingey T, Shu J, Smuczek J, Pope J. Meta-analysis of healing and prevention of digital ulcers in systemic sclerosis. Arthritis Care Res (Hoboken). 2013 Sep;65(9):1460-71. doi: 10.1002/acr.22018. — View Citation

Tsifetaki 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. — View Citation

Valentini G, D'Angelo S, Della Rossa A, Bencivelli W, Bombardieri S. European Scleroderma Study Group to define disease activity criteria for systemic sclerosis. IV. Assessment of skin thickening by modified Rodnan skin score. Ann Rheum Dis. 2003 Sep;62(9):904-5. doi: 10.1136/ard.62.9.904. No abstract available. — View Citation

Valentini G, Della Rossa A, Bombardieri S, Bencivelli W, Silman AJ, D'Angelo S, Cerinic MM, Belch JF, Black CM, Bruhlmann P, Czirjak L, De Luca A, Drosos AA, Ferri C, Gabrielli A, Giacomelli R, Hayem G, Inanc M, McHugh NJ, Nielsen H, Rosada M, Scorza R, Stork J, Sysa A, van den Hoogen FH, Vlachoyiannopoulos PJ. European multicentre study to define disease activity criteria for systemic sclerosis. II. Identification of disease activity variables and development of preliminary activity indexes. Ann Rheum Dis. 2001 Jun;60(6):592-8. doi: 10.1136/ard.60.6.592. — View Citation

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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. — View Citation

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* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Digital Ulcers	The change in the number of finger ulcers and the appearance or not of new ones.	0-18 months
Secondary	Modified Rodnan Skin Score (?RSS)	The change in the rating on the modified Rodnan leather scale	18 months
Secondary	Raynaud's Condition Score RCS	The change in the rating on the Raynaud scale	0-18 months
Secondary	EUSTAR activity index	The change in the score on the EUSTAR activity scale	0-18 months
Secondary	Adverse Events, AE	Number of Adverse Events during the study period	0-18 months

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