Raynaud Phenomenon
Conditions
Keywords
Pathological Conditions, Signs and Symptoms, Blood circulation
Brief summary
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.
Interventions
DRUGUdenafil or Amlodipine
Amlodipine 10mg daily then Udenafil 100 mg daily OR Udenafil 100 mg daily then Amlodipine 10mg daily
Sponsors
Dong-A Pharmaceutical Co., Ltd.
Seoul National University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| RP Attacks Per Day | baselin and 4 weeks | Change in RP frequency after amlodipine and udenafil number of RP attack per day 0 -- unlimited. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the RP Duration | baseline and 4 weeks | Change in the average RP duration in minutes (min) per attack. 0 -- unlimited |
| Change in Health Assessment Questionnaire (HAQ) | 0 and 4 weeks | Ordinal scale 0-10 0 good 10 bad |
| Change in Physician's Global Assessment on Visual Analogue Scale (VAS) | at 0 (baseline) and 4 weeks (after treatment) | 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. |
| Change in Raynaud's Condition Score (RCS) | baseline and 4 weeks | 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 |
| Change in Peak Systolic Flow (cm/Sec) | baseline and 4 weeks | Change in digital artery flow velocity in proper palmar digital artery in cm/sec. 0-unlimited |
| Time-averaged Peak Velocity (cm/Sec) | baseline and 4 weeks | changes in the averaged blood flow (Time-averaged peak velocity) Blood flow in cm/sec 0 - unlimited. |
| Dorsal-digital-difference. | baseline and 4 weeks | The temperature difference between finger tips and dorsum of same hand. range 0 - unlimited in degree celcius. |
| Change in Digital Ulcer Number | baseline and 4 weeks | 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. |
Countries
South Korea
Participant flow
Recruitment details
Recruitment begin Jan 13 2011 until Mar 15 2011. Location: Rheumatology outpatient clinic at Seoul National University Hospital, Seoul, Korea.
Pre-assignment details
30 Patients were initially recruited, but an error occurred in obtaining informed consent and this one was withdrawn.
Participants by arm
| Arm | Count |
|---|---|
| Amlodipine-Udenafil (AU) Arm Amlodipine first, then Udenafil | 14 |
| Udenafil-Amlodipine (UA) Arm Udenafil first, then Amlodipine | 12 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention (Week 1-4) | Adverse Event | 1 | 0 |
| First Intervention (Week 1-4) | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Amlodipine-Udenafil (AU) Arm | Udenafil-Amlodipine (UA) Arm | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 12 Participants | 26 Participants |
| Age Continuous | 49.6 years STANDARD_DEVIATION 14 | 52.3 years STANDARD_DEVIATION 10.3 | 50.9 years STANDARD_DEVIATION 12.3 |
| Disease subtype diffuse SSc | 10 participant | 7 participant | 17 participant |
| Disease subtype Localized systemic sclerosis (SSc) | 1 participant | 2 participant | 3 participant |
| Disease subtype Mixed connective tissue disease | 1 participant | 2 participant | 3 participant |
| Disease subtype Sjogren's disease | 2 participant | 1 participant | 3 participant |
| Prior use of vasodilator angiotensin receptor blocker | 2 Participant | 0 Participant | 2 Participant |
| Prior use of vasodilator calcium channel blocker | 1 Participant | 4 Participant | 5 Participant |
| Prior use of vasodilator No prior use | 10 Participant | 7 Participant | 17 Participant |
| Prior use of vasodilator Pentyxifylline | 1 Participant | 1 Participant | 2 Participant |
| Region of Enrollment Korea, Republic of | 14 participants | 12 participants | 26 participants |
| RP duration | 8.8 years STANDARD_DEVIATION 8.7 | 5.6 years STANDARD_DEVIATION 2.3 | 7.3 years STANDARD_DEVIATION 6.6 |
| Sex: Female, Male Female | 13 Participants | 11 Participants | 24 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 26 | 19 / 26 |
| serious Total, serious adverse events | 0 / 26 | 2 / 26 |
Outcome results
Primary
RP Attacks Per Day
Change in RP frequency after amlodipine and udenafil number of RP attack per day 0 -- unlimited.
Time frame: baselin and 4 weeks
Population: 14 patients in UA arm + 12 patients in AU arm
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine | RP Attacks Per Day | -0.5 attacks per day | Standard Deviation 1.4 |
| Udenafil | RP Attacks Per Day | -0.5 attacks per day | Standard Deviation 0.9 |
Secondary
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.
Time frame: baseline and 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine | Change in Digital Ulcer Number | 0.1 Digital ulcers | Standard Deviation 0.4 |
| Udenafil | Change in Digital Ulcer Number | 0.1 Digital ulcers | Standard Deviation 0.3 |
Secondary
Change in Health Assessment Questionnaire (HAQ)
Ordinal scale 0-10 0 good 10 bad
Time frame: 0 and 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine | Change in Health Assessment Questionnaire (HAQ) | 0.1 units on a scale | Standard Deviation 0.4 |
| Udenafil | Change in Health Assessment Questionnaire (HAQ) | -0.1 units on a scale | Standard Deviation 0.3 |
Secondary
Change in Peak Systolic Flow (cm/Sec)
Change in digital artery flow velocity in proper palmar digital artery in cm/sec. 0-unlimited
Time frame: baseline and 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine | Change in Peak Systolic Flow (cm/Sec) | -19.9 cm/sec | Standard Deviation 145.9 |
| Udenafil | Change in Peak Systolic Flow (cm/Sec) | 63.2 cm/sec | Standard Deviation 170.2 |
Secondary
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.
Time frame: at 0 (baseline) and 4 weeks (after treatment)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine | Change in Physician's Global Assessment on Visual Analogue Scale (VAS) | -0.9 units on a scale | Standard Deviation 1.4 |
| Udenafil | Change in Physician's Global Assessment on Visual Analogue Scale (VAS) | -1.5 units on a scale | Standard Deviation 1.6 |
Secondary
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
Time frame: baseline and 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine | Change in Raynaud's Condition Score (RCS) | -0.5 units on a scale | Standard Deviation 1.5 |
| Udenafil | Change in Raynaud's Condition Score (RCS) | -0.3 units on a scale | Standard Deviation 1 |
Secondary
Change in the RP Duration
Change in the average RP duration in minutes (min) per attack. 0 -- unlimited
Time frame: baseline and 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine | Change in the RP Duration | -1.1 min per attack | Standard Deviation 5.9 |
| Udenafil | Change in the RP Duration | -1.4 min per attack | Standard Deviation 11.4 |
Secondary
Dorsal-digital-difference.
The temperature difference between finger tips and dorsum of same hand. range 0 - unlimited in degree celcius.
Time frame: baseline and 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine | Dorsal-digital-difference. | -0.7 degree celcius. | Standard Deviation 3.2 |
| Udenafil | Dorsal-digital-difference. | -1.4 degree celcius. | Standard Deviation 3.3 |
Secondary
Time-averaged Peak Velocity (cm/Sec)
changes in the averaged blood flow (Time-averaged peak velocity) Blood flow in cm/sec 0 - unlimited.
Time frame: baseline and 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine | Time-averaged Peak Velocity (cm/Sec) | -17.3 cm/sec | Standard Deviation 98.6 |
| Udenafil | Time-averaged Peak Velocity (cm/Sec) | 33.4 cm/sec | Standard Deviation 123 |