Sildenafil for Swimming-Induced Pulmonary Edema (SIPE) Prevention

NCT ID: NCT03686813

Last Updated: 2022-11-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-15
• Study Completion Date: 2021-10-29

Brief 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.

Conditions

Edema, Pulmonary; Immersion; Diving

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Each participant will be studied with active drug and placebo.

Group Type: PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type: DRUG

Placebo

Sildenafil

Sildenafil 50 mg orally one hour (once) before immersed exercise

Group Type: ACTIVE_COMPARATOR

Sildenafil Citrate

Intervention Type: DRUG

Oral sildenafil, 50 mg

Interventions

Sildenafil Citrate

Oral sildenafil, 50 mg

Intervention Type: DRUG

Placebo Oral Tablet

Placebo

Intervention Type: DRUG

Other Intervention Names

Viagra; Revatio

Eligibility Criteria

Inclusion Criteria

• Healthy volunteers between 18 and 45 years
• History of swimming-induced pulmonary edema

Exclusion Criteria

• Pregnant women
• Significant heart valve disease
• Cardiomyopathy
• Uncontrolled hypertension
• Coronary artery disease
• Obstructive lung disease
• VO2max <25 mL/kg as estimated by the University of Houston Non-Exercise Test
• Previous adverse reaction to sildenafil
• Use of antihypertensives or other drugs that are known to interact adversely with sildenafil (e.g. nitrates, alpha adrenergic blockers)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

United States Department of Defense

FED

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

Pro00100971

Identifier Type: -

Identifier Source: org_study_id