Digital Ulcers, Raynaud's Phenomenon, Scleroderma
Conditions
Keywords
Raynaud's phenomenon, ischemic ulcers, digital ulcers, digital infarcts, gangrene, vasodilators, endothelial dysfunction, scleroderma
Brief summary
Raynaud's phenomenon (RP) associated with scleroderma is a difficult problem to treat. Many patients develop ischemic digital ulcers due to severe RP that causes considerable morbidity and adversely affects the quality of life. In an earlier study, we have observed marked improvement in RP attacks and rapid healing of digital ulcers following therapy with phosphodiesterase V inhibitor, Tadalafil. In the present multicentric study we aim to study the efficacy of Tadalafil in patients continuing to have RP attacks despite using at least one or more vasodilators.
Interventions
DRUGTadalafil
Tab Tadalafil, 20 mg alternate day for 8 weeks
DRUGPlacebo
Tab Placebo every alternate day for 8 weeks
Sponsors
Institute of Postgraduate Medical Education and Research
Post Graduate Institute of Medical Education and Research, Chandigarh
Army Hospital Research And Referral, India
Sanjay Gandhi Postgraduate Institute of Medical Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Male or female subjects between the ages of 18 years and 65 years will be selected for the study if they have a clinical diagnosis of Raynaud's phenomenon secondary to systemic sclerosis (scleroderma) despite being on vasodilator therapy. Raynaud's phenomenon is defined as a history of cold sensitivity associated with colour changes of cyanosis or pallor. Patients with a history of at least 4 attacks per week during two-week pre-trial period even with treatment with other vasodilators will be recruited. Patients fulfilling the diagnostic criteria of scleroderma (as per American College of Rheumatology criteria) or having presence of at least 3 of the 5 features of the CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias)will be invited to participate in the study.
Exclusion criteria
Patients with: * Symptomatic orthostatic hypotension, * Evidence of current malignancy, * History of sympathectomy, * Upper extremity deep vein thrombosis or lymphedema within 3 months, * Recent surgical procedure requiring general anesthesia, * Acute Myocardial Infarction, unstable angina, strokes and transient ischemic attacks within the past three months, * Smoking, * Use of any investigational drug within 30 days of the study sessions, * Use of medications that might interfere with tadalafil like nitrates and alpha adrenergic blockers that have vasoactive effects, and patients taking potent inhibitors of CYP3A4 such as ritonavir, ketoconazole, and itraconazole, erythromycin, itraconazole, and grapefruit juice, * Patients taking alcohol, * Patients with bleeding disorders * Significant active peptic ulceration, * Current pregnancy, * Current breast-feeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Daily frequency, duration and severity of Raynaud's phenomenon | Baseline and 8 weeks |
| Appearance or healing of digital ulcers | Baseline and 8 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Improvement in quality of life | Baseline and 8 weeks |
| Improvement in health assessment questionnaire | Baseline and 8 weeks |
| Improvement in flow mediated dilatation | Baseline and 8 weeks |
| Improvement in biomarkers of endothelial dysfunction | Baseline and 8 weeks |
| Improvement in scleroderma specific health assessment questionnaire | Baseline and 8 weeks |
Countries
India
Outcome results
None listed