Therapeutic Effect of Sildenafil in Patients With Coronary Vasospasm

April 10, 2017 updated by: Udo Sechtem

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

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?

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Stuttgart, Germany, 70376
        • Robert-Bosch-Krankenhaus

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

48 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of coronary vasospasm in spite of medical treatment
Time Frame: After inclusion of last patient
After inclusion of last patient

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Udo Sechtem

Investigators

  • Study Director: Udo Sechtem, MD, Robert Bosch-Krankenhaus Stuttgart

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2007

Primary Completion (Actual)

December 31, 2009

Study Completion (Actual)

December 31, 2009

Study Registration Dates

First Submitted

March 29, 2007

First Submitted That Met QC Criteria

March 30, 2007

First Posted (Estimate)

April 2, 2007

Study Record Updates

Last Update Posted (Actual)

April 12, 2017

Last Update Submitted That Met QC Criteria

April 10, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RBK091

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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