Clinical trial NCT01291199: Effects of Vardenafil on Clinical Symptoms and Peripheral Blood Flow in Patients With Raynaud's Syndrome
Official title: Double-blind, Placebo-controlled Cross-over Study to Investigate the Effects of the Phosphodiesterase 5-inhibitor Vardenafil on Periphery Blood Flow and Clinical Symptoms of Patients With Raynaud's Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Raynaud Syndrome
Keywords: double-blind placebo controlled cross-over study
Lead sponsor: University of Cologne
Sponsor class: OTHER
First posted: 2011-02-08
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether vardenafil is effective in improving clinical symptoms and peripheral blood flow in patients with primary and secondary Raynaud phenomenon.


Eligibility criteria: 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

Primary outcomes:
measure: Change in the Raynaud's Condition Score
timeFrame: daily for 18 weeks
Secondary outcomes:
measure: Number of participants with adverse events as a Measure of Safety and Tolerability
timeFrame: daily for 18 weeks
measure: Digital blood flow
timeFrame: at baseline, one hour after drug intake and after six weeks on therapy
Other outcomes:
Locations:
city: Cologne
country: Germany
facility: University of Cologne - Heart Center
state: NRW
Study officials:
affiliation: University of Cologne
name: Stephan Rosenkranz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Caglayan E, Huntgeburth M, Karasch T, Weihrauch J, Hunzelmann N, Krieg T, Erdmann E, Rosenkranz S. Phosphodiesterase type 5 inhibition is a novel therapeutic option in Raynaud disease. Arch Intern Med. 2006 Jan 23;166(2):231-3. doi: 10.1001/archinte.166.2.231.