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Blood Pressure Interaction Between Sildenafil and Sublingual Glyceryl Trinitrate (GTN) in Men With Angina

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: NCT00479908
Recruitment Status : Completed
First Posted : May 30, 2007
Last Update Posted : May 30, 2007
Information provided by:
University of Edinburgh

Brief Summary:
The purpose of the study is to determine for how long sildenafil potentiates the blood pressure reduction that occurs with glyceryl trinitrate in men with angina.

Condition or disease Intervention/treatment Phase
Angina Pectoris Drug: Sildenafil citrate Drug: Glyceryl trinitrate Phase 4

Detailed Description:

By producing a mediator known as cGMP, nitric oxide (NO) potently dilates blood vessels. Nitrates, such as glyceryl trinitrate (GTN), are drugs that release NO (NO donors) and are widely used in the treatment and prevention of angina. Sildenafil is an effective treatment for male penile erectile dysfunction that inhibits the breakdown cGMP. When given alone it causes modest reductions in BP in healthy people and patients with cardiovascular disease. By their synergistic actions, co-administration of NO donors with sildenafil can result in large reductions in BP in patients with angina, a population at increased risk of developing erectile dysfunction. As a result, it is recommended that the two drugs not be co-administered within 24 hours of one another.

Previous studies have defined the effect of nitrates at 60 min after administration of sildenafil, the time of likely maximum interaction. However, emergency medicine physicians would value evidence of a balance of risks from which to make a personal clinical judgement about when they might consider giving GTN in a patient presenting with a severe episode of angina who has recently received sildenafil. Evidence on which to base such a judgement is currently not available. However, we have recently completed a study, showing that the interaction of GTN (0.4 mg spray) after sildenafil (100 mg) lasts less than 4 hours in healthy subjects. Whilst the findings would probably be similar for patients with angina, this question now needs to be investigated directly in order to ensure the generalisability of this work and address an important unresolved clinical issue.

Subjects will be asked to refrain from using short-acting nitrates for 24 hours and long acting nitrates for 72 hours before the start of the study. On the morning of each study visit subjects will take their normal medications, including anti-anginals, as soon as they wake up at home. They will also eat a light breakfast at home before coming to the research unit.

Subjects will attend 4 study visits, each separated by at least 5 days. At study visit 1 GTN will be administered 4 and 8 hours after oral sildenafil or matched placebo. At visit 2 GTN will be administered 4 and 8 hours after the alternative treatment (sildenafil or placebo). The order in which sildenafil and placebo are given will be randomised. At study visit 3 GTN will be administered 1 and 6 hours after sildenafil or placebo. Finally, at visit 4 GTN will be administered 1 and 6 hours after the alternative treatment (sildenafil or placebo). As with visits 1 and 2, the order in which sildenafil and placebo are given will be randomised.

Regular single measures of sitting and standing (after 2 min standing) BP and heart rate (HR) will be recorded at baseline and before and for 40 minutes after each GTN administration. Venous blood samples (20 mL) will be taken at baseline and immediately before and 40 min after each GTN administration for later determination of plasma concentrations of sildenafil and its active metabolite, UK-103,320.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: Investigation of the Time Course of the Interaction of the Hypotensive Effects of Sildenafil Citrate and Sublingual Glyceryl Trinitrate (GTN) in Men With Stable Angina Pectoris
Study Start Date : January 2004
Actual Study Completion Date : September 2005

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Angina

Primary Outcome Measures :
  1. Effect of combined sildenafil and GTN on mean maximum reduction in blood pressure

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   30 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Male
  • Stable angina with one of:
  • Classical history of exertional angina pectoris
  • Previous diagnostic exercise test
  • Angiographic evidence of CAD
  • Aged 30 to 80 years
  • Weight between 60 and 100 Kg

Exclusion Criteria:

  • Regular treatment with long-acting nitrates or nicorandil where these cannot be withdrawn 72 hours prior to the study
  • Myocardial infarction, unstable angina, stroke or transient cerebral ischaemia within 3 months
  • Systolic BP > 170 mmHg or diastolic BP > 100 mmHg
  • Systolic BP < 100 mmHg or diastolic BP < 60 mmHg
  • Orthostatic hypotension (> 20 mmHg fall in systolic BP on standing)
  • Diabetes treated with oral hypoglycaemic agents or insulin
  • Any clinically significant disease other than stable angina, excepting other cardiovascular disease risk factors, e.g. smoking, hypercholesterolaemia and diet-controlled diabetes
  • Taking any drug that interacts with sildenafil
  • Evidence of drug abuse

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): NCT00479908

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United Kingdom
University of Edinburgh
Edinburgh, Scotland, United Kingdom, EH4 2XU
Sponsors and Collaborators
University of Edinburgh
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Principal Investigator: James J Oliver, MBChB University of Edinburgh

Layout table for additonal information Identifier: NCT00479908    
Other Study ID Numbers: LREC/2003/8/35
First Posted: May 30, 2007    Key Record Dates
Last Update Posted: May 30, 2007
Last Verified: May 2007
Keywords provided by University of Edinburgh:
Blood pressure
Phosphodiesterase type 5
Organic nitrate
Glyceryl trinitrate
Drug interaction
Additional relevant MeSH terms:
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Angina Pectoris
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Chest Pain
Neurologic Manifestations
Signs and Symptoms
Sildenafil Citrate
Citric Acid
Sodium Citrate
Calcium Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Urological Agents