High Altitude Pulmonary EdemaPhase 4NCT00627965
Randomized, Controlled Trial of Regular Sildenafil Citrate in the Prevention of Altitude Illness
A Phase 4 study testing Sildenafil citrate in people with High Altitude Pulmonary Edema and Acute Mountain Sickness, run by Altitude Physiology Expeditions.
Trial summary
The purpose of this study is to determine whether regular oral use of sildenafil citrate can prevent or attenuate high altitude illnesses. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- High Altitude Pulmonary Edema, Acute Mountain Sickness
- What is being tested?
- Sildenafil citrate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- No sites listed yet
- Study dates
- Mar 2003to Feb 2008
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Participant in Apex 2 high altitude expedition
Who cannot join
- Previous history of high altitude pulmonary edema
About this study
The purpose of this study is to determine whether regular oral use of sildenafil citrate can prevent or attenuate high altitude illnesses.
Read the detailed description
High altitude pulmonary oedema (HAPE) is a life-threatening non-cardiogenic lung injury precipitated by exaggerated pulmonary hypertension. The incidence of this rapidly progressive illness, among the estimated 40 million visitors to high altitude each year, may be as high as 0.5-2.0%. The pathogenesis of HAPE is multifactorial and may include impaired clearance of alveolar fluid, increased pulmonary vascular permeability and genetic susceptibility. Elevated pulmonary artery pressure (PAP) caused by hypoxic pulmonary vasoconstriction (HPV) is a key prerequisite for the development of HAPE and thus the reduction of PAP is paramount in the prophylaxis and treatment of this devastating illness.
Nitric oxide (NO) is thought to play an important role in the exaggerated HPV that characterises HAPE. NO, constitutively produced in the lung by the enzyme endothelial nitric oxide synthase (eNOS), increases intracellular cGMP in pulmonary vascular smooth muscle and activates cGMP-dependent protein kinase, ultimately leading to a reduction in intracellular calcium and smooth muscle relaxation. HAPE-susceptible individuals exhale less NO during both normobaric and hypobaric hypoxia suggesting that a deficiency of NO synthesis may predispose to HAPE. At high altitude, inhaled NO causes a significantly greater reduction in the systolic PAP of HAPE-susceptible individuals compared to its effect on the PAP of HAPE-resistant subjects, but the administration of NO would be impractical in the field. Most recently, work has concentrated on another target in the NO pathway.
Sildenafil citrate is an orally active, potent and selective phosphodiesterase type-5 (PDE-5) inhibitor. PDE-5 is the predominant enzyme responsible for degradation of cGMP in the lung. In a small sea level study, Zhao et al. demonstrated that pre-treatment with sildenafil nearly completely abolished the pulmonary vasopressor response to breathing hypoxic gas in healthy humans. More recently, studies at altitude have also shown reductions in pulmonary artery systolic pressure (PASP) in subjects taking sildenafil at high altitude.
One potential problem with the use of sildenafil at altitude is that PDE-5 inhibitors may worsen symptoms of acute mountain sickness (AMS). Headache is a defining symptom in AMS and is a prominent side effect of sildenafil.
We conducted a double-blind placebo-controlled randomised trial to assess the effect of regular sildenafil administration on PASP and Lake Louise AMS score at an altitude of 5200 m.
- Being tested
- Sildenafil citrate, Placebo
- Keywords
- Sildenafil citrate, Prevention, High Altitude Pulmonary Edema, Acute Mountain Sickness, Healthy Lowland Subjects, Pulmonary Artery Systolic Pressure
- Medical subject headings
- Altitude Sickness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sildenafil citrateDrug
50mg tds
PlaceboDrug
Placebo tds
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Sildenafil citrate Receives: Drug: Sildenafil citrate |
| 2 | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pulmonary Artery Systolic Pressure (PASP)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2008 (estimated)
- Study startMar 2003
- Study completionFeb 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for High Altitude Pulmonary EdemaStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Altitude Physiology Expeditions
- Sponsor type
- University, hospital or other
- Collaborators
- University of Edinburgh
- Investigators
- Matthew Bates, Principal investigator, Altitude Physiology Expeditions
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00627965
- Sponsor's protocol ID
- Sildenafil1
- Status last verified
- Feb 2008
- First submitted
- 24 Feb 2008
- Last updated
- 4 Mar 2008
- Results posted
- No
- Data monitoring committee
- No
Publications
MacCormick IJ, Somner J, Morris DS, MacGillivray TJ, Bourne RR, Huang SS, MacCormick A, Aspinall PA, Baillie JK, Thompson AA, Dhillon B. Retinal vessel tortuosity in response to hypobaric hypoxia. High Alt Med Biol. 2012 Dec;13(4):263-8. doi: 10.1089/ham.2011.1097.
PubMed 23270443Bates MG, Thompson AA, Baillie JK, Sutherland AI, Irving JB, Hirani N, Webb DJ. Sildenafil citrate for the prevention of high altitude hypoxic pulmonary hypertension: double blind, randomized, placebo-controlled trial. High Alt Med Biol. 2011 Fall;12(3):207-14. doi: 10.1089/ham.2011.0007.
PubMed 21962063
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Controlled Trial of Regular Sildenafil Citrate in the Prevention of Altitude Illness
- ClinicalTrials.gov ID
- NCT00627965
- Acronym / sponsor ID
- Sildenafil1
- Keywords
- Sildenafil citrate, Prevention, High Altitude Pulmonary Edema, Acute Mountain Sickness, Healthy Lowland Subjects, Pulmonary Artery Systolic Pressure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Altitude Physiology ExpeditionsUniversity, hospital or other
- Collaborators
- University of Edinburgh
- Study start
- Mar 2003
- Study completion
- Feb 2008 (actual)
- First posted
- 4 Mar 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether regular oral use of sildenafil citrate can prevent or attenuate high altitude illnesses.
Detailed description
High altitude pulmonary oedema (HAPE) is a life-threatening non-cardiogenic lung injury precipitated by exaggerated pulmonary hypertension. The incidence of this rapidly progressive illness, among the estimated 40 million visitors to high altitude each year, may be as high as 0.5-2.0%. The pathogenesis of HAPE is multifactorial and may include impaired clearance of alveolar fluid, increased pulmonary vascular permeability and genetic susceptibility. Elevated pulmonary artery pressure (PAP) caused by hypoxic pulmonary vasoconstriction (HPV) is a key prerequisite for the development of HAPE and thus the reduction of PAP is paramount in the prophylaxis and treatment of this devastating illness.
Nitric oxide (NO) is thought to play an important role in the exaggerated HPV that characterises HAPE. NO, constitutively produced in the lung by the enzyme endothelial nitric oxide synthase (eNOS), increases intracellular cGMP in pulmonary vascular smooth muscle and activates cGMP-dependent protein kinase, ultimately leading to a reduction in intracellular calcium and smooth muscle relaxation. HAPE-susceptible individuals exhale less NO during both normobaric and hypobaric hypoxia suggesting that a deficiency of NO synthesis may predispose to HAPE. At high altitude, inhaled NO causes a significantly greater reduction in the systolic PAP of HAPE-susceptible individuals compared to its effect on the PAP of HAPE-resistant subjects, but the administration of NO would be impractical in the field. Most recently, work has concentrated on another target in the NO pathway.
Sildenafil citrate is an orally active, potent and selective phosphodiesterase type-5 (PDE-5) inhibitor. PDE-5 is the predominant enzyme responsible for degradation of cGMP in the lung. In a small sea level study, Zhao et al. demonstrated that pre-treatment with sildenafil nearly completely abolished the pulmonary vasopressor response to breathing hypoxic gas in healthy humans. More recently, studies at altitude have also shown reductions in pulmonary artery systolic pressure (PASP) in subjects taking sildenafil at high altitude.
One potential problem with the use of sildenafil at altitude is that PDE-5 inhibitors may worsen symptoms of acute mountain sickness (AMS). Headache is a defining symptom in AMS and is a prominent side effect of sildenafil.
We conducted a double-blind placebo-controlled randomised trial to assess the effect of regular sildenafil administration on PASP and Lake Louise AMS score at an altitude of 5200 m.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Sildenafil citrateSildenafil citrate |
| 2 | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- Participant in Apex 2 high altitude expedition
Key exclusion criteria (1 listed)
- Previous history of high altitude pulmonary edema
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 citrate50mg tds | Drug | 1 |
| PlaceboPlacebo tds | Drug | 2 |
Primary outcome
Pulmonary Artery Systolic Pressure (PASP)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Derived from this study: PubMed 23270443MacCormick IJ, Somner J, Morris DS, MacGillivray TJ, Bourne RR, Huang SS, MacCormick A, Aspinall PA, Baillie JK, Thompson AA, Dhillon B. Retinal vessel tortuosity in response to hypobaric hypoxia. High Alt Med Biol. 2012 Dec;13(4):263-8. doi: 10.1089/ham.2011.1097.
- Derived from this study: PubMed 21962063Bates MG, Thompson AA, Baillie JK, Sutherland AI, Irving JB, Hirani N, Webb DJ. Sildenafil citrate for the prevention of high altitude hypoxic pulmonary hypertension: double blind, randomized, placebo-controlled trial. High Alt Med Biol. 2011 Fall;12(3):207-14. doi: 10.1089/ham.2011.0007.
- Research group website coordinating future studiesLink provided by the sponsor.
Related trials for High Altitude Pulmonary Edema
Not yet recruiting
High-flow Nasal Cannula Oxygen Therapy Versus Conventional Oxygen Therapy in Children High-altitude Pulmonary Edema
High-altitude Pulmonary Edema
Not yet recruitingObservational study
Optimization of Two-Indicator Screening Protocol for Neonatal Congenital Heart Disease at High Altitude
Neonatal Congenital Heart Disease
Not yet recruiting
Assessment of Total Pulmonary Resistance sPAP/CO Between High Altitude HA vs. Sea Level LA in Healthy Individuals H
High Altitude, Healthy Adult
Not yet recruiting
Assessment of Total Pulmonary Resistance sPAP/CO Between Sea Level LA vs. High Altitude HA After Re-ascent in Patients With Pulmonary Arterial Hypertension PAH
Pulmonary Arterial Hypertension (PAH), Pulmonary Vascular Disease
Not yet recruiting
Assessment of Total Pulmonary Resistance sPAP/CO Between Sea Level LA vs. High Altitude HA After Re-ascent in Healthy Individuals
High Altitude, Healthy
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.
Matthew Bates principal investigator
Altitude Physiology Expeditions
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sildenafil citrate in people with High Altitude Pulmonary Edema and Acute Mountain Sickness, run by Altitude Physiology Expeditions.
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 1 inclusion and 1 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 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Pulmonary Artery Systolic Pressure (PASP). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00627965, which also lists 2 linked publications.
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 4 Mar 2008.