Efficacy Study of PDE-5 Inhibitor and Calcium Channel Inhibitor for the Treatment of Secondary Raynaud Phenomenon

Study Overview
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Brief Summary
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The prevalence of Raynaud phenomenon (RP), a reversible vaso-constriction with skin discoloration, is 5-10% in general population. Often conventional measures such as warming up or minimizing exposure to cold are not enough and many patients require treatment with a vasodilator therapy. A recent study showed a good efficacy and safety profile of sildenafil, a selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) in RP. Here, the investigators aim to examine the efficacy and safety of Udenafil, a newer PDE5 inhibitor, as compared to amlodipine, a well known calcium channel blocker, in the treatment of secondary RP in Korean patients.

Official Title
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Comparison of Phosphodiesterase-5 Inhibitor and Calcium Channel Inhibitor for the Treatment of Secondary Raynaud Phenomenon, Double Blind, Randomized, Cross-over Trial

Conditions
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Raynaud Phenomenon

Intervention / Treatment
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* Drug: Udenafil or Amlodipine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: secondary Raynaud's phenomenon Exclusion Criteria: primary raynaud phenomenon active infection hypersensitivity to PDE5 inhibitor or Calcium Chanel Blocker (CCB) elevated AST/ALT (3 times above the upper normal limit) severe renal failure patients on nitrite or nitric oxide (NO) donor treatment recent history of cerebrovascular accidents, acute myocardial infarction, or coronary artery bypass surgery hypotension (less than 90/50 mmHg) or uncontrolled hypertension

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amlodipine-Udenafil (AU) arm<br>Amlodipine 10mg PO QD for 4 weeks, washout period, then Udenafil 100mg PO QD for 4 weeks | Drug: Udenafil or Amlodipine<br>* Amlodipine 10mg daily then Udenafil 100 mg daily OR Udenafil 100 mg daily then Amlodipine 10mg daily<br>|
| Experimental: Udenafil-Amlodipine (UA) arm<br>Udenafil 100mg PO QD for 4 weeks, washout period, then Amlodipine 10mg PO QD for 4 weeks | Drug: Udenafil or Amlodipine<br>* Amlodipine 10mg daily then Udenafil 100 mg daily OR Udenafil 100 mg daily then Amlodipine 10mg daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RP Attacks Per Day | Change in RP frequency after amlodipine and udenafil number of RP attack per day 0 -- unlimited. | baselin and 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Raynaud's Condition Score (RCS) | change in the RCS. RCS combines daily activty, frequency, duration and severity as well as impact of RP attack (Measuring disease activity and functional status in patients with scleroderma and Raynaud's phenomenon, Merkel et al,Arthritis Rheum. 2002 Sep;46(9):2410-20). Range 0-10 ordinal scale 0..good 10.. bad | baseline and 4 weeks | 
| Change in the RP Duration | Change in the average RP duration in minutes (min) per attack. 0 -- unlimited | baseline and 4 weeks | 
| Change in Health Assessment Questionnaire (HAQ) | Ordinal scale 0-10 0 good 10 bad | 0 and 4 weeks | 
| Change in Physician's Global Assessment on Visual Analogue Scale (VAS) | Physician's global assessment (PGA) on VAS assesses the overall condition of the patient. The scale ranges from 0 - 10, with 0 being good and 10 bad. As such, change in the GPA measures the change in the patient's condition from the baseline. negative value (decrease in value) means improvement. | at 0 (baseline) and 4 weeks (after treatment) | 
| Change in Digital Ulcer Number | 0 - unlimited. Number of digital ulcers in all fingers are counted by the investigators and recorded at each visit. The number of ulcers in all fingers indirectly reflect the extent of critical ischemia. As such. the decrease in digital ulcer number reflects positive response to treatment (=better blood flow), whereas the increase ulcer numbers indicates worsening finger ischemia from baseline. | baseline and 4 weeks | 
| Change in Peak Systolic Flow (cm/Sec) | Change in digital artery flow velocity in proper palmar digital artery in cm/sec. 0-unlimited | baseline and 4 weeks | 
| Time-averaged Peak Velocity (cm/Sec) | changes in the averaged blood flow (Time-averaged peak velocity) Blood flow in cm/sec 0 - unlimited. | baseline and 4 weeks | 
| Dorsal-digital-difference. | The temperature difference between finger tips and dorsum of same hand. range 0 - unlimited in degree celcius. | baseline and 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pathological Conditions, Signs and Symptoms, Blood circulation