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Sildenafil for Swimming-Induced Pulmonary Edema (SIPE) Prevention

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03686813
Recruitment Status : Suspended (Due to COVID-19 pandemic research stoppage)
First Posted : September 27, 2018
Last Update Posted : May 20, 2020
Sponsor:
Collaborator:
United States Department of Defense
Information provided by (Responsible Party):
Duke University

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.

Condition or disease Intervention/treatment Phase
Edema, Pulmonary Immersion Diving Drug: Sildenafil Citrate Drug: Placebo Oral Tablet Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Double blind, randomized
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Placebo controlled
Primary Purpose: Prevention
Official Title: Sildenafil for Prevention of Swimming-Induced Pulmonary Edema (SIPE)
Actual Study Start Date : July 15, 2019
Estimated Primary Completion Date : October 1, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Edema

Arm Intervention/treatment
Placebo Comparator: Placebo
Each participant will be studied with active drug and placebo.
Drug: Placebo Oral Tablet
Placebo

Active Comparator: Sildenafil
Sildenafil 50 mg orally one hour (once) before immersed exercise
Drug: Sildenafil Citrate
Oral sildenafil, 50 mg
Other Name: Viagra




Primary Outcome Measures :
  1. Pulmonary edema [ Time Frame: During or immediately after exercise in cold water ]
    One or more of: hypoxemia, productive cough, pulmonary edema on chest radiograph, wheezing on chest auscultation


Secondary Outcome Measures :
  1. Dyspnea [ Time Frame: During or immediately after exercise in cold water ]
    Voluntary premature cessation of exercise due to shortness of breath

  2. Spirometry [ Time Frame: Immediately after exercise in cold water ]
    Post-exercise 10% decrease in forced vital capacity (FVC) or forced expiratory volume in one second (FEV1)

  3. Ultrasound lung assessment [ Time Frame: Immediately after exercise in cold water ]
    'Comet tails' seen on ultrasound of the lungs



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03686813


Locations
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United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
United States Department of Defense
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Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT03686813    
Other Study ID Numbers: Pro00100971
First Posted: September 27, 2018    Key Record Dates
Last Update Posted: May 20, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Data will be published in the open literature

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Pulmonary Edema
Edema
Signs and Symptoms
Lung Diseases
Respiratory Tract Diseases
Sildenafil Citrate
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Urological Agents