Improvement of Myocardial Blood Flow by PhosphoDiesterase 5 Inhibition in Coronary Artery Disease (SYDNEY)

Expanded access is temporarily not available for this treatment.
Sponsor:
Information provided by:
Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT01406535
First received: July 29, 2011
Last updated: NA
Last verified: January 2011
History: No changes posted
  Purpose

The aim of this study is to prospectively investigate if intermittent Phosphodiesterase 5 inhibition for 15 weeks improves myocardial perfusion by angiogenesis in patients with therapy refractory myocardial ischemia due to coronary artery disease judged to be unsuitable for surgical or percutaneous revascularisation. For proof of efficacy the following tests will be performed at baseline and one day and 4 weeks after discontinuation of therapy: Exercise tolerance will be evaluated by bicycle exercise testing. Blood tests will be performed to evaluate markers of angiogenesis (endothelial progenitor cells, vascular endothelial growth factor, basic fibroblast growth factor). The improvement of myocardial perfusion will be tested functionally as increase of coronary flow reserve by positron emission tomography. Moreover, changes in ventricular function, symptoms and quality of life will be assessed.


Condition Intervention
Therapy Refractory Myocardial Ischemia
Coronary Artery Disease
Unsuitable for Surgical or Percutaneous Revascularisation
Drug: Vardenafil
Other: Placebo

Study Type: Expanded Access     What is Expanded Access?
Official Title: Sustained Improvement of MYocardial Blood Flow by Intermittent PhosphoDiesterase 5 INhibition in REfractory Coronary ArterY Disease Suggests Enhanced Angiogenesis (SYDNEY)

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Intervention Details:
    Drug: Vardenafil
    5 mg vardenafil per os twice daily
    Other: Placebo
    5 mg placebo per os twice daily
Detailed Description:

This study is designed as a randomized, double-blind, placebo controlled monocentric study.

Patients will be randomized to two groups; PDE5 inhibitor (vardenafil) or placebo taken as one tablet twice per day for 15 weeks. The analyses will be performed under blinded conditions by external experts not having any direct contact to the investigators or the patients.

Patients with severe coronary artery disease who are judged to be unsuitable for surgical revascularization because of a bad general state of health or unsuitable for percutaneous revascularization because of the bad morphology of coronary arteries by an expert panel of interventionists and cardiac surgeons are eligible for this study. Eligible patients meeting inclusion criteria will be invited for participation. At the screening visit (Visit -1) demographic data, medical history, and concomitant medication are documented, vital signs are checked, a physical examination, an ECG, and a routine laboratory test is performed. After giving written informed consent for participation in the study, the patient is randomized to one of the two study groups - PDE5 inhibitor (vardenafil) or placebo taken as one pill twice per day for 15 weeks. Within three weeks after this screening visit, baseline efficacy tests are performed. After the last baseline test the study medication is distributed to the patient (Visit 0). During the treatment phase follow-up visits are scheduled after week 1, 3, 6, and 12 (Visit 1-4). Between week 13 and 15 the same efficacy tests as performed at baseline will be repeated. The final visit after the last efficacy test terminates the active study phase at week 15 (Visit 5). During visit 0 to 5 a clinical examination, an ECG, and clinical routine laboratory parameters (blood chemistry, blood cell count, and coagulation parameters) of the patient are performed.

For proof of efficacy the following tests will be performed at baseline and one day and 4 weeks after discontinuation of therapy: Exercise tolerance will be evaluated by bicycle exercise testing. Blood tests will be performed to evaluate markers of angiogenesis (endothelial progenitor cells, vascular endothelial growth factor, basic fibroblast growth factor). The improvement of myocardial perfusion will be tested functionally as increase of coronary flow reserve by positron emission tomography. Moreover, changes in ventricular function, symptoms and quality of life will be assessed.

Endpoints of this study are:

Primary Endpoint:

- Total exercise duration (bicycle exercise testing)

Secondary Endpoints:

  • Time to 1mm ST-segment depression (bicycle exercise testing)
  • Time to limiting angina (bicycle exercise testing)
  • Myocardial blood flow (PET)
  • Left ventricular ejection fraction (PET)
  • Mean angina frequency per week
  • Score Seattle Angina Questionnaire
  • Natriuretic peptides
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Criteria

Inclusion Criteria:

  • Stable angina pectoris
  • Evidence for myocardial ischemia according to the presence of one or more of the followings:
  • Typical angina during exercise test or
  • Significant reversible perfusion defects on dipyridamole myocardial radionuclide study
  • Coronary artery disease of at least one large epicardial coronary artery with ≥70% stenosis remaining from which new collaterals/vessels could be supplied
  • Coronary artery disease judged to be unsuitable for surgical or percutaneous revascularisation ƒdue to extensive atherosclerosis
  • Optimized anti-ischemic drug therapy (including beta-blocker therapy with at least 50% target dose)

Subject must be willing and able to give informed consent Eligible patients must fulfill all 6 inclusion criteria.

Exclusion Criteria:

  • STEMI or NSTEMI within the past 3 months
  • Revascularisation procedures within the last 3 months
  • Severely reduced systolic left ventricular function EF < 30%
  • Systolic blood pressure <120mmHg
  • Chronic renal insufficiency with a serum creatinine >2.5mg/dl
  • Diabetes mellitus with proliferative retinopathy
  • Diagnosed or suspected cancer
  • Chronic inflammatory disease
  • Therapy with nitrates and nicorandil
  • Women who are pregnant or lactating
  • Patients with a total occluded vessel and reversible perfusion defects at the marginal zone of scare tissue if they have no additional stenosed vessels causing significant reversible perfusion defects.
  • Patients with a total occluded vessel and perfusion defect at rest despite evidence of vital myocardium, if they have no additional stenosed vessels causing significant reversible perfusion defects.

Eligible patients must demonstrate none of the exclusion criteria.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01406535

Locations
Austria
Rudolf Berger, MD
Vienna, Austria, 1090
Sponsors and Collaborators
Medical University of Vienna
  More Information

No publications provided

Responsible Party: Rudolf Berger, MD, Medical University of Vienna, Department of Internal Medicine, Division of cardiology
ClinicalTrials.gov Identifier: NCT01406535     History of Changes
Other Study ID Numbers: MUWCard23022011
Study First Received: July 29, 2011
Last Updated: July 29, 2011
Health Authority: Austria: Federal Ministry for Health and Women

Keywords provided by Medical University of Vienna:
Phosphodiesterase 5 inhibition
myocardial perfusion
angiogenesis
coronary artery disease
therapy refractory

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Ischemia
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Pathologic Processes
Vardenafil
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents

ClinicalTrials.gov processed this record on July 31, 2014