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The Clinical And Subclinical Effects on Arterial Stiffness of Bosentan in Patients With Systemic Sclerosis (CEASESTIFF)

U

University Medical Center Groningen (UMCG)

Status and phase

Completed
Phase 4

Conditions

Scleroderma, Systemic

Treatments

Drug: bosentan

Study type

Interventional

Funder types

Other
Industry

Identifiers

NCT02480335
NL49919.042.14

Details and patient eligibility

About

The aim of the study is to investigate whether bosentan added to usual care improves arterial stiffness after 3 months as measured as the pulse wave velocity (PWV) of the medium and large arteries corrected for blood pressure changes in patients with systemic sclerosis (SSc) with digital ulcers (DU). Patients will be randomized into a group with usual care and bosentan (n=10) or usual care only (n=10). PWV will be assessed at baseline, 3 months and 12 months.

Full description

Rationale: Digital ischemia is a major problem in patients with Raynaud's phenomenon (RP), especially in those with underlying connective tissue diseases such as systemic sclerosis (SSc). SSc is hallmarked by microvascular disease which can be assessed by nailfold capillary microscopy (NCM) to identify specific capillary patterns. However, it appears that vascular damage is not restricted to the capillaries, but may also extend to more upstream hand and forearm arteries. This may not only be reflected by clinically relevant structural abnormalities such as obliteration, but also by decreases in arterial function. The best characterised in RP is the occurrence of vasospasms after cold exposure. However, evidence points out that major stiffening of the arteries also occurs, potentially exaggerating digital ischemia and other vascular complications in SSc.

Objective: To investigate whether bosentan added to usual care improves arterial stiffness after 3 months as measured as the pulse wave velocity of the medium and large arteries corrected for blood pressure changes in patients with systemic sclerosis with digital ulcers.

Intervention:

Group 1: Usual care AND bosentan 62.5 mg twice daily, titrated to 125 mg twice daily after one month if tolerated (n=10) Group 2: Usual care only (n=10)

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Bosentan is a registered product in the Netherlands. In this study, it will be used within its indication and not in combination with other products for which it has not been registered. Therefore no additional unknown uncertainties and increased overall risk are applicable for the investigational product. In the usual care group, treatment will not differ from clinical practice. To minimize the risk of patients not receiving the most appropriate treatment in the control group, regular visits and lab assessments are planned. Patients are allowed to start with bosentan in the usual care group if indicated by the treating physician. The study will consist of one screening and three study visits. During the latter, patients clinical signs and symptoms will be assessed, vascular lab will be performed, blood will be drawn, and subjects be asked to fill in questionnaire, all of which will have a duration of no more than 2 hours per visits. In total 3 times 24cc of blood will be collected, preferably in combination will routine lab assessments. These measures render the risks acceptable and the burden minimal for the subjects participating in the study.

Enrollment

20 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • 18 years or older
  • Systemic sclerosis based on the 2013 American College of Rheumatology/European League Against Rheumatism criteria
  • Raynaud's phenomenon
  • A history of digital ulcer disease
  • Assessable Pulse Wave Velocity measurement at baseline
  • Written informed consent

Exclusion criteria

  • Hypersensitivity to the active substance or to any of the excipients
  • Systolic blood pressure lower than 85 mmHg
  • Moderate to severe hepatic impairment, i.e., Child-Pugh class B or C
  • Baseline values of liver aminotransferases, i.e., aspartate aminotransferases and/or alanine aminotransferases, greater than 3 times the upper limit of normal
  • Concomitant use of cyclosporine A
  • Pregnancy
  • Women of child-bearing potential who are not using reliable methods of contraception
  • Significant peripheral vascular disease as the sole consequence of atherosclerotic disease due to conventional vascular risk factors and coagulopathy

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

20 participants in 2 patient groups

Usual care and bosentan
Experimental group
Description:
Usual care and also treatment with bosentan.
Treatment:
Drug: bosentan
Usual care
No Intervention group
Description:
Usual care only.

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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