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Sponsors and Collaborators: |
University of Edinburgh Pfizer |
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Information provided by: | University of Edinburgh |
ClinicalTrials.gov Identifier: | NCT00479908 |
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 | Intervention | Phase |
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Angina Pectoris |
Drug: Sildenafil citrate Drug: Glyceryl trinitrate |
Phase IV |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Pharmacodynamics Study |
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 |
Enrollment: | 20 |
Study Start Date: | January 2004 |
Study Completion Date: | September 2005 |
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.
Ages Eligible for Study: | 30 Years to 80 Years |
Genders Eligible for Study: | Male |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
United Kingdom, Scotland | |
University of Edinburgh | |
Edinburgh, Scotland, United Kingdom, EH4 2XU |
Principal Investigator: | James J Oliver, MBChB | University of Edinburgh |
Study ID Numbers: | LREC/2003/8/35 |
Study First Received: | May 29, 2007 |
Last Updated: | May 29, 2007 |
ClinicalTrials.gov Identifier: | NCT00479908 History of Changes |
Health Authority: | United Kingdom: Medicines and Healthcare Products Regulatory Agency |
Blood pressure Angina Sildenafil Phosphodiesterase type 5 |
Organic nitrate Glyceryl trinitrate Drug interaction |
Vasodilator Agents Heart Diseases Myocardial Ischemia Citric Acid Angina Pectoris Vascular Diseases Pain Sildenafil |
Cardiovascular Agents Ischemia Antihypertensive Agents Chest Pain Nitroglycerin Signs and Symptoms Phosphodiesterase Inhibitors |
Vasodilator Agents Heart Diseases Molecular Mechanisms of Pharmacological Action Myocardial Ischemia Angina Pectoris Vascular Diseases Enzyme Inhibitors Pain Sildenafil |
Cardiovascular Agents Pharmacologic Actions Chest Pain Nitroglycerin Signs and Symptoms Phosphodiesterase Inhibitors Therapeutic Uses Cardiovascular Diseases |