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

Information source: University Medical Center Groningen
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Scleroderma, Systemic

Intervention: bosentan (Drug)

Phase: Phase 4

Status: Not yet recruiting

Sponsored by: University Medical Center Groningen

Summary

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=20) or usual care only (n=20). PWV will be assessed at baseline, 3 months and 12 months.

Clinical Details

Official title: The Clinical Efficacy And Subclinical Effects on Arterial STIFFNESS of Bosentan Therapy Added to Usual Care in Patients With Systemic Sclerosis With Digital Ulcers

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Mean of right and left carotid-femoral arterial (i.e. aortic) Pulse Wave Velocity (cfPWV)

Secondary outcome:

Mean of right and left carotid-femoral arterial (i.e. aortic) Pulse Wave Velocity (cfPWV)

Right carotid-brachial arterial PWV (cbPWV)

Left carotid-brachial arterial PWV (cbPWV)

Right carotid-radial arterial PWV (crPWV)

Left carotid-radial arterial PWV (crPWV)

Local PWV of the right radial artery (rPWV)

Local PWV of the left radial artery (rPWV)

Local PWV of the right brachial artery (bPWV)

Local PWV of the left brachial artery (bPWV)

Microangiopathy Evolution Score (MES)

Capillaroscopic Skin Ulcer Risk Index (CSURI)

Prognostic Index for Digital Lesions (PILD)

Mean widened capillaries of 8 fingers (dig 2-5)

Mean giant capillaries of 8 fingers (dig 2-5)

Mean capillary density of 8 fingers (dig 2-5)

Mean loop width of 8 fingers (dig 2-5)

Blood flow in the hands in region of interest (ROI) 1: distal of the proximal interphalangeal (PIP) joint of the 3 middle fingers

Blood flow in the hands in ROI 2: distal of the metacarpal joints and proximal of the PIP joint

Blood flow in the hands in ROI 3: the hand proximal of the metacarpal joints

Skin Autofluorescence

Number of new digital ulcers

Time to healing of digital ulcers

Urine albumin/creatinine ratio (ACR)

Plasma N-terminal of the prohormone brain natriuretic peptide (NT-proBNP)

Serum levels of matrix metalloproteinase 3

Serum levels of matrix metalloproteinases 9

Serum levels of tissue inhibitors of metalloproteinases (TIMP)

Blood pressure of the brachial artery

Modified Rodnan Skin Score (mRSS)

Scleroderma Health Assessment Questionnaire (SHAQ)

Short Form (36)

Detailed 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=20) Group 2: Usual care only (n=20) 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.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Locations and Contacts

University Medical Center Groningen, Groningen 9700 RB, Netherlands; Not yet recruiting
Douwe J Mulder, MD, PhD, Phone: +31-50-3612350, Email: d.j.mulder@umcg.nl
Andries J Smit, MD, PhD, Email: a.j.smit@umcg.nl
Douwe J. Mulder, MD, PhD, Principal Investigator
Andries J. Smit, MD, PhD, Principal Investigator
Anniek M. van Roon, Sub-Investigator
Saskia C. van de Zande, Sub-Investigator
Additional Information

Starting date: June 2015
Last updated: June 19, 2015

Page last updated: August 23, 2015

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