Sildenafil for Swimming-Induced Pulmonary Edema (SIPE) Prevention
Condition: Edema, Pulmonary; Immersion; Diving
MeSH terms: Pulmonary Edema; Edema
Study type: Interventional
Phase: Phase 2

Summary: 
      This trial is testing the effectiveness of a single oral dose of sildenafil (50 mg) taken 1
      hour before a provocative event on the subsequent development of swimming-induced pulmonary
      edema.
    

Detailed description: 
      Immersion pulmonary edema (also known as swimming-induced pulmonary edema, SIPE) is a
      condition in which the lungs fill with fluid (pulmonary edema) during a dive or vigorous
      swim, causing cough with bloody sputum, shortness of breath and reduced blood oxygen levels.
      In the Navy this usually occurs in young, healthy individuals such as SEAL and Special
      Warfare Combatant-Craft trainees. SIPE generally resolves spontaneously within 24 hours but
      it can be fatal. It is believed that SIPE is responsible for some deaths in civilians during
      triathlons. This proposal aims to test a drug to prevent SIPE.

      Depending upon severity, the prevalence of SIPE is reported in up to 60% during 2.4-3.6 km
      open sea swimming trials in the Israel Defense Force. In SEAL training in the US
      approximately 40 cases per year (around 3%) have been reported, more commonly during winter,
      when it is observed in up to 5% of trainees. Return to duty time can be up to 7 days. SIPE
      also affects other groups of highly fit individuals such as triathletes. In susceptible
      individuals it tends to recur, thus a preventive medicine would be useful for both Navy SEALs
      and civilians.

      The aim of this study will be to provide the Navy an FDA-approved drug that can be used to
      prevent SIPE. The investigators hypothesize that sildenafil administration to
      SIPE-susceptible individuals one hour before a swim in cold water will reduce or eliminate
      the risk of SIPE. The method to be used to test this hypothesis will be a 40-minute period of
      exercise immersed to the neck in 20°C water, a test that results in SIPE symptoms in the
      majority of susceptible individuals. The investigators plan to study 20 individuals who have
      previously experienced SIPE. Each volunteer will be tested twice. Either sildenafil or an
      inactive drug (placebo) administered in random order will be given prior to each exercise.
      For each participant exercise periods will be performed at least 7 days apart. The identity
      of the drug and placebo will be concealed from the investigators and the volunteers until the
      end of the study. The number of instances in which SIPE manifestations after sildenafil and
      placebo will then be compared.

      Availability of a drug that can prevent SIPE would provide the Navy with a useful tool that
      could be administered to SEALs who have experienced SIPE prior to critical missions. It would
      also be useful for civilians who have experienced SIPE but wish to continue with the
      precipitating exercise such as swimming or competing in triathlons, and also for patients
      with heart failure for whom swimming induces shortness of breath or pulmonary edema.
    

Intervention name(s): Sildenafil Citrate; Placebo Oral Tablet
Intervention type(s): Drug; Drug
Intervention description(s): Oral sildenafil, 50 mg; Placebo
Other intervention name(s): Viagra; Revatio
Intervention MeSH terms: Sildenafil Citrate
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Double blind, randomized
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention