Edema, PulmonaryPhase 2NCT03686813
Sildenafil for Swimming-Induced Pulmonary Edema (SIPE) Prevention
A Phase 2 study testing Sildenafil Citrate in people with Edema, Pulmonary and Immersion, run by Duke University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Edema, Pulmonary, Immersion, Diving
- What is being tested?
- Sildenafil Citrate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jul 2019to 29 Oct 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy volunteers between 18 and 45 years
- History of swimming-induced pulmonary edema
Who cannot join
- Pregnant women
- Significant heart valve disease
- Cardiomyopathy
- Uncontrolled hypertension
- Coronary artery disease
- Obstructive lung disease
Show all 9Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: Sildenafil for Prevention of Swimming-Induced Pulmonary Edema (SIPE)
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.
Read the 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
- Being tested
- Sildenafil Citrate, Placebo Oral Tablet
- Medical subject headings
- Pulmonary Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sildenafil CitrateDrug
Also called Viagra, Revatio
Oral sildenafil, 50 mg
Placebo Oral TabletDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Each participant will be studied with active drug and placebo. Receives: Drug: Placebo Oral Tablet |
| Sildenafil | Active comparator | Sildenafil 50 mg orally one hour (once) before immersed exercise Receives: Drug: Sildenafil Citrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Pulmonary Edema
One or more of: hypoxemia, productive cough, pulmonary edema on chest radiograph, wheezing on chest auscultation.
Measured: During or immediately after exercise in cold water, approximately one hour and 40 minutes
Secondary outcomes (4)
Number of Participants With Dyspnea Leading to Voluntary Premature Cessation of Exercise
Voluntary premature cessation of exercise due to shortness of breath.
Measured: During or immediately after exercise in cold water, approximately one hour and 40 minutes
Number of Participants With Post-exercise 10% Decrease in Forced Vital Capacity (FVC) or Forced Expiratory Volume in One Second (FEV1) as Measured by Spirometry
Post-exercise 10% decrease in forced vital capacity (FVC) or forced expiratory volume in one second (FEV1).
Measured: Immediately after exercise in cold water, approximately one hour and 40 minutes
Number of Participants With "Comet Tails" Seen on Ultrasound of the Lungs
A "comet tail" artefact is a short path reverberation artefact that weakens with each reverberation, resulting in a vertical echogenic artefact that rapidly fades as it continues in to the ultrasound image.
Measured: Immediately after exercise in cold water, approximately one hour and 40 minutes
Number of Participants Who Found the Exercise Easiest When Given Sildenafil Citrate Versus When Given Placebo
Measured: Immediately after exercise in cold water, approximately one hour and 40 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2018
- Study start15 Jul 2019
- Primary completion29 Oct 2021
- Study completion29 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Edema, PulmonaryStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Double blind, randomized
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03686813
- Sponsor's protocol ID
- Pro00100971
- Status last verified
- Oct 2022
- First submitted
- 24 Sep 2018
- Last updated
- 22 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Data will be published in the open literature
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sildenafil for Prevention of Swimming-Induced Pulmonary Edema (SIPE)
- ClinicalTrials.gov ID
- NCT03686813
- Acronym / sponsor ID
- Pro00100971
- Conditions
- Edema, Pulmonary, Immersion, Diving
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- 15 Jul 2019 (actual)
- Primary completion
- 29 Oct 2021 (actual)
- Study completion
- 29 Oct 2021 (actual)
- First posted
- 27 Sep 2018 (actual)
- Results
- Posted 22 Nov 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double blind, randomized
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo Oral TabletEach participant will be studied with active drug and placebo. |
| Sildenafil | Active comparator | Drug: Sildenafil CitrateSildenafil 50 mg orally one hour (once) before immersed exercise |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Healthy volunteers between 18 and 45 years
- History of swimming-induced pulmonary edema
Key exclusion criteria (9 listed)
- Pregnant women
- Significant heart valve disease
- Cardiomyopathy
- Uncontrolled hypertension
- Coronary artery disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sildenafil CitrateAlso: Viagra, RevatioOral sildenafil, 50 mg | Drug | Sildenafil |
| Placebo Oral TabletPlacebo | Drug | Placebo |
Primary outcome
Number of Participants With Pulmonary Edema
Time frame: During or immediately after exercise in cold water, approximately one hour and 40 minutes
One or more of: hypoxemia, productive cough, pulmonary edema on chest radiograph, wheezing on chest auscultation.
4 secondary outcomes
Number of Participants With Dyspnea Leading to Voluntary Premature Cessation of Exercise
Time frame: During or immediately after exercise in cold water, approximately one hour and 40 minutes
Number of Participants With Post-exercise 10% Decrease in Forced Vital Capacity (FVC) or Forced Expiratory Volume in One Second (FEV1) as Measured by Spirometry
Time frame: Immediately after exercise in cold water, approximately one hour and 40 minutes
Number of Participants With "Comet Tails" Seen on Ultrasound of the Lungs
Time frame: Immediately after exercise in cold water, approximately one hour and 40 minutes
Number of Participants Who Found the Exercise Easiest When Given Sildenafil Citrate Versus When Given Placebo
Time frame: Immediately after exercise in cold water, approximately one hour and 40 minutes
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided. Data will be published in the open literature
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sildenafil Citrate in people with Edema, Pulmonary and Immersion, run by Duke University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Pulmonary Edema (time frame: During or immediately after exercise in cold water, approximately one hour and 40 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2022.