Effects of Vardenafil on Clinical Symptoms and Peripheral Blood Flow in Patients With Raynaud's Syndrome

Inclusion criteria

• raynaud-syndrome (primary or secondary) > 1 year duration
• age ≥ 18 years; ≤ 80 years
• informed consent
• a negative pregnancy test in women of child-bearing age

Exclusion criteria

• any unstable organic, psychiatric or addictive disease, which - in the opinion of the investigators - might result in an unsuccessful / unreliable participation or premature termination of the trial
• known contraindications against PDE 5-inhibitors (such as intolerance, therapy with nitrates or inhibitors of CYP3A4, etc.)
• extensive necrosis of the finger tips
• pigmentary retinopathy
• verification as a HbsAg or hepatitis C carrier
• unstable angina
• heart failure (NYHA III or IV)
• valve defects of higher degree (particularly aortic stenosis and hypertrophic obstructive cardiomyopathy)
• myocardial infarction, stroke or life-threatening cardiac arrhythmias within the last 6 months
• uncontrolled atrial fibrillation / -flutter with a heart rate > 100 bpm
• prolonged QTc-interval (> 450 msec)
• congenital long-QT-syndrome
• hypokalemia
• severe acute or chronic liver disease, which might lead to priapism (sickle cell anemia, leucemia)
• hemophilia
• active peptic ulcers
• arterial hypotension (systolic blood pressure at rest <90 mmHg) or
• arterial hypertension(systolic blood pressure at rest >170 mmHg or diastolic blood pressure at rest >110 mmHg)
• malignancy within the last 5 years (except squamous or basal cell skin cancer)
• patients with injuries of the spinal cord or central nervous system
• patients with severe chronic kidney disease (creatinin clearance < 30 ml)
• patients with mild to severe liver disease (Child-Pugh A-C)
• Age below 18 or above 80
• prohibited concomitant medication during the study:

• nitrates or other NO-donators (including amylnitrit)
• anticoagulative drugs except inhibitors of thrombocyte function
• androgens (such as testosterone) or anti-androgens
• strong inhibitors of cytochrome P4503A4:
• very potent HIV-Protease-inhibitors (ritonavir, indinavir)
• anti-mycotic like itraconazole and ketoconazole (topical applications are allowed)
• erythromycin
• grapefruit-juice or products containing grapefruit-juice

• other study medications (including placebo) up to 30 days before study inclusion
• therapy of erectile dysfunction(including sildenafil, sublingual apomorphin, MUSE®, intracavernous injections or vacuum pumps) or other therapies of erectile dysfunction within 4 weeks and during the trial period
• nebivolol
• alpha-blockers
• Calcium antagonists
• medications prolonging the QT-interval
• abnormal lab tests like:
• serum-creatinine > 3 mg/dl at visit 1
• GOT and GPT > 3 x reference limit set
• diabetes mellitus with a HbA1c > 9%
• patients who are not willing to disclaim a therapy of their erectile dysfunction with vacuum pumps, intravenous injections, sildenafil or other therapies during the trial
• severe migraine (more than once a moth during the last 6 months)
• intolerance to the study medication
• patients who are not able to understand the information and informed consent due to a mental disorder or linguistic barriers
• persons who are living in a institution directly under federal government control due to a court order
• patients who refuse to renounce drinking grapefruit juice during the trial
• women who are pregnant or lactating
• women who are not protected from a pregnancy (intake of oral contraceptives alone in insufficient; highly effective methods of birth control have to be used with a failure rate <1%; barriers: implants, intrauterine-devices (IUD´s),diaphragm, condoms, abstinence, partner is vasectomized, spermicides)
• patients who participated in other interventional studies within 30 days of study inclusion