Blood Pressure Interaction Between Sildenafil and Sublingual Glyceryl Trinitrate (GTN) in Men With Angina
Information source: University of Edinburgh
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Angina Pectoris
Intervention: Sildenafil citrate (Drug); Glyceryl trinitrate (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: University of Edinburgh Official(s) and/or principal investigator(s):
James J Oliver, MBChB, Principal Investigator, Affiliation: University of Edinburgh
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.
Clinical Details
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 design: Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Treatment
Primary outcome: Effect of combined sildenafil and GTN on mean maximum reduction in blood pressure
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.
Eligibility
Minimum age: 30 Years.
Maximum age: 80 Years.
Gender(s): Male.
Criteria:
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
Locations and Contacts
University of Edinburgh, Edinburgh, Scotland EH4 2XU, United Kingdom
Additional Information
Starting date: January 2004
Last updated: May 29, 2007
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