Randomized, Controlled Trial of Regular Sildenafil Citrate in the Prevention of Altitude Illness
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ClinicalTrials.gov Identifier: NCT00627965 |
Recruitment Status
:
Completed
First Posted
: March 4, 2008
Last Update Posted
: March 4, 2008
|
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
High Altitude Pulmonary Edema Acute Mountain Sickness | Drug: Sildenafil citrate Drug: Placebo | Phase 4 |
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 Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 62 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Triple (Participant, Investigator, Outcomes Assessor) |
Primary Purpose: | Prevention |
Official Title: | Randomized, Controlled Trial of Regular Sildenafil Citrate in the Prevention of Altitude Illness |
Study Start Date : | March 2003 |
Actual Study Completion Date : | February 2008 |

Arm | Intervention/treatment |
---|---|
Experimental: 1
Sildenafil citrate
|
Drug: Sildenafil citrate
50mg tds
|
Placebo Comparator: 2
Placebo
|
Drug: Placebo
Placebo tds
|
- Pulmonary Artery Systolic Pressure (PASP)

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Ages Eligible for Study: | Child, Adult, Senior |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- Participant in Apex 2 high altitude expedition
Exclusion Criteria:
- Previous history of high altitude pulmonary edema

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): NCT00627965
Principal Investigator: | Matthew Bates | Altitude Physiology Expeditions |
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Director, Altitude Physiology Expeditions |
ClinicalTrials.gov Identifier: | NCT00627965 History of Changes |
Other Study ID Numbers: |
Sildenafil1 |
First Posted: | March 4, 2008 Key Record Dates |
Last Update Posted: | March 4, 2008 |
Last Verified: | February 2008 |
Keywords provided by Altitude Physiology Expeditions:
Sildenafil citrate Prevention High Altitude Pulmonary Edema |
Acute Mountain Sickness Healthy Lowland Subjects Pulmonary Artery Systolic Pressure |
Additional relevant MeSH terms:
Altitude Sickness Pulmonary Edema Hypertension, Pulmonary Lung Diseases Respiratory Tract Diseases Respiration Disorders Citric Acid Sildenafil Citrate Anticoagulants |
Calcium Chelating Agents Chelating Agents Sequestering Agents Molecular Mechanisms of Pharmacological Action Vasodilator Agents Phosphodiesterase 5 Inhibitors Phosphodiesterase Inhibitors Enzyme Inhibitors Urological Agents |