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Therapeutic Effect of Sildenafil in Patients With Coronary Vasospasm

This study has suspended participant recruitment.
(Patient study insurance expired)
Sponsor:
Information provided by:
Robert Bosch Gesellschaft für Medizinische Forschung mbH
ClinicalTrials.gov Identifier:
NCT00454714
First received: March 29, 2007
Last updated: July 20, 2011
Last verified: July 2011
History of Changes
  Purpose

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 Intervention Phase
Coronary Vasospasm
 Drug: single dose Sildenafil
Drug: Single dose placebo
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Robert Bosch Gesellschaft für Medizinische Forschung mbH:

Primary Outcome Measures:
  • Incidence of coronary vasospasm in spite of medical treatment [ Time Frame: After inclusion of last patient ] [ Designated as safety issue: No ]

Estimated Enrollment: 26
Study Start Date: March 2007
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00454714

Locations
Germany
Robert-Bosch-Krankenhaus
Stuttgart, Germany, 70376
Sponsors and Collaborators
Robert Bosch Gesellschaft für Medizinische Forschung mbH
Investigators
Study Director: Udo Sechtem, MD Robert-Bosch-Krankenhaus Stuttgart
  More Information

No publications provided

Responsible Party: Robert Bosch Hospital, Division of Cardiology
ClinicalTrials.gov Identifier: NCT00454714     History of Changes
Other Study ID Numbers: RBK091
Study First Received: March 29, 2007
Last Updated: July 20, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

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

ClinicalTrials.gov processed this record on May 16, 2013