Blood Pressure Interaction Between Sildenafil and Sublingual Glyceryl Trinitrate (GTN) in Men With Angina
Condition: Angina Pectoris
MeSH terms: Angina Pectoris
Study type: Interventional
Phase: Phase 4

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.
    

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.
    

Intervention name(s): Sildenafil citrate; Glyceryl trinitrate
Intervention type(s): Drug; Drug
Intervention MeSH terms: Sildenafil Citrate; Nitroglycerin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double
Primary purpose: Treatment
Keywords: Blood pressure; Angina; Sildenafil; Phosphodiesterase type 5; Organic nitrate; Glyceryl trinitrate; Drug interaction