Therapeutic Effect of Sildenafil in Patients With Coronary Vasospasm

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00454714
Recruitment Status : Withdrawn (Study not started)
First Posted : April 2, 2007
Last Update Posted : April 12, 2017
Information provided by (Responsible Party):
Udo Sechtem, Robert Bosch Gesellschaft für Medizinische Forschung mbH

Brief Summary:

This will be a prospective, phase IIIb, double-blind and randomized trial testing the effect of single dose sildenafil application in patients with coronary vasospasm compared to placebo application.

The target variable to be tested is the degree of coronary vasoconstriction in response to intracoronary ACh application (in addition to clinical chest pain) which will be imaged by coronary angiography and measured using quantitative coronary angiography software.

Main objective: Has sildenafil the potency to inhibit the induction of coronary vasospasm by intracoronary ACh-application in patients with proven coronary artery spasm?

Secondary objective: Which degree of coronary vasospasm inhibition can be achieved with sildenafil?

Condition or disease Intervention/treatment Phase
Coronary Vasospasm Drug: single dose Sildenafil Drug: Single dose placebo Phase 3

Detailed Description:

Coronary artery spasm is an abrupt severe vasoconstrictor response which may occur spontaneously in normal and diseased coronary arteries. It may result in myocardial ischemia and may be provoked by various stimuli such as acetylcholine (ACh). Coronary vasospasm is involved in the pathogenesis of Prinzmetal's angina, acute myocardial infarction or sudden cardiac death due to ventricular arrythmias and chest pain symptoms associated with viral myocarditis.

The precise cellular and molecular mechanisms of coronary vasospasm have not yet been elucidated. The most often suggested but competing explanations for this disease are coronary endothelial dysfunction secondary to impaired nitric oxide production versus coronary smooth muscle cell hyperreactivity with or without additional endothelial dysfunction. As the precise cellular mechanism is currently unknown a large group of people can currently not be treated appropriately despite the use of nitrates and calcium antagonists.

Sildenafil is a phosphodiesterase(PDE)-5 inhibitor approved for the treatment of both erectile dysfunction and pulmonary hypertension. PDE-5 has been shown to be also present and play an important vasomotor role in the coronary vessel wall. Application of the inhibitor sildenafil has been shown to increase the resting coronary artery diameter. Furthermore, atherosclerotic coronary artery segments which vasoconstrict following intracoronary ACh-application vasodilate following the application of sildenafil when ACh-testing is repeated. Other studies are also suggesting an improved endothelial function after sildenafil application for both the coronary and the peripheral vasculature.

Taken together, sildenafil is expected to have a positive effect on coronary vasomotility. Whether sildenafil can totally prevent the occurrence of coronary vasospasm or at least decrease the severity of vasospasm has not been studied so far. Thus, the aim of this study is to analyse the possible anti-spastic effects of sildenafil in patients suffering from coronary vasospasm.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Application of Sildenafil in Patients With Documented Coronary Vasospasm to Explore the Pathophysiology of Coronary Vasospasm and the Therapeutic Effect of Sildenafil in Patients Suffering From Coronary Vasospasm
Study Start Date : March 1, 2007
Actual Primary Completion Date : December 31, 2009
Actual Study Completion Date : December 31, 2009

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: A
Sildenafil arm
Drug: single dose Sildenafil
Application of a single dose Sildenafil

Placebo Comparator: B
Placebo arm
Drug: Single dose placebo
Application of a single dose placebo

Primary Outcome Measures :
  1. Incidence of coronary vasospasm in spite of medical treatment [ Time Frame: After inclusion of last patient ]

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • age ≥ 50y
  • Framingham risk score < 10%
  • no contraindication to sildenafil application
  • clinical history of atypical angina pectoris
  • exclusion of significant coronary artery disease (stenosis ≥ 50%) by coronary angiography
  • documented coronary spasm by ACh-testing in at least one coronary artery segment
  • written informed consent

Exclusion Criteria:

  • existing contraindication to sildenafil application
  • significant coronary artery disease (≥ 50%)
  • valvular, inflammatory, dilative or other cardiomyopathies
  • congestive heart failure (left ventricular ejection fraction < 60%) of any reason
  • need for therapeutic treatment with nitrates or intake of any nitrates in the last 24h before coronary angiography
  • participation in another clinical trial at the moment or in the last 30 days
  • hypotonic blood pressure (<90/50mmHg)
  • hepatic insufficiency (> Child-Pugh-classification A)
  • renal insufficiency with a GFR < 60ml/min- pregnancy or lactation
  • not able to consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00454714

Stuttgart, Germany, 70376
Sponsors and Collaborators
Udo Sechtem
Study Director: Udo Sechtem, MD Robert Bosch-Krankenhaus Stuttgart

Responsible Party: Udo Sechtem, Prof. Udo Sechtem, Robert Bosch Gesellschaft für Medizinische Forschung mbH Identifier: NCT00454714     History of Changes
Other Study ID Numbers: RBK091
First Posted: April 2, 2007    Key Record Dates
Last Update Posted: April 12, 2017
Last Verified: April 2017

Additional relevant MeSH terms:
Coronary Vasospasm
Coronary Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Sildenafil Citrate
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents