Effects of Normobaric Hypoxia During Exercise in Patients With Pulmonary Hypertension With/Without Sildenafil

Study Overview
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Brief Summary
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To study the effect of acute normobaric hypoxia during exercise in patients with pulmonary hypertension with/without Sildenafil

Official Title
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Hemodynamic Effects of Acute Normobaric Hypoxia During Exercise in Patients With Pulmonary Hypertension: Single-center Randomized Controlled Trial

Conditions
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Hypertension, Pulmonary

Intervention / Treatment
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* Other: Normobaric hypoxia (FiO2 15%)
* Other: Placebo-ambient air (FiO2 21%)
* Other: Normobaric hypoxia (FiO2 15%) under Sildenafil
* Other: Placebo-ambient air (FiO2 21%) under Sildenafil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent as documented by signature (Appendix Informed Consent Form) PH class I (PAH) or IV (CTEPH) diagnosed according to guidelines: mean pulmonary artery pressure >20 mmHg, pulmonary vascular resistance ≥3 wood units, pulmonary arterial wedge pressure ≤15 mmHg during baseline measures at the diagnostic right-heart catheterization Exclusion Criteria: resting partial pressure of oxygen <8 kilopascal at Zürich altitude on ambient air exposure to an altitude >1000 m for ≥3 nights during the last 2 weeks before the study inability to follow the procedures of the study patients who take nitrates other clinically significant concomitant end-stage disease (e.g., renal failure, hepatic dysfunction)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Normobaric hypoxia (FiO2 15%)<br>Inhalation of deoxygenated air through an altitude simulator (Altitrainer), for approx. 1/2 hour given by a facemask, first at rest and then during exercise. | Other: Normobaric hypoxia (FiO2 15%)<br>* Inhalation of deoxygenated air through an altitude simulator (Altitrainer), for approx. 1/2 hour given by a facemask, first at rest and then during exercise.<br>|
| Sham Comparator: Placebo-ambient air (FiO2 21%)<br>Inhalation of room air through an altitude simulator (Altitrainer), for approx. 1/2 hour given by a facemask, first at rest and then during exercise. | Other: Placebo-ambient air (FiO2 21%)<br>* Inhalation of room air through an altitude simulator (Altitrainer), for approx. 1/2 hour given by a facemask, first at rest and then during exercise.<br>|
| Experimental: Normobaric hypoxia (FiO2 15%) under Sildenafil<br>Inhalation of deoxygenated air through an altitude simulator (Altitrainer), for approx. 1/2 hour given by a facemask, first at rest and then during exercise. | Other: Normobaric hypoxia (FiO2 15%) under Sildenafil<br>* Inhalation of deoxygenated air through an altitude simulator (Altitrainer), for approx. 1/2 hour given by a facemask, first at rest and then during exercise.<br>|
| Active Comparator: Placebo-ambient air (FiO2 21%) under Sildenafil<br>Inhalation of room air through an altitude simulator (Altitrainer), for approx. 1/2 hour given by a facemask, first at rest and then during exercise. | Other: Placebo-ambient air (FiO2 21%) under Sildenafil<br>* Inhalation of room air through an altitude simulator (Altitrainer), for approx. 1/2 hour given by a facemask, first at rest and then during exercise.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mean pulmonary artery pressure (mPAP) / cardiac output (CO) | Difference in mPAP/CO during exercise between tests under normoxia/hypoxia with/without Sildenafil | 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in pulmonary arterial pressure | Differences in pulmonary arterial pressure at rest and during exercise under normoxia/hypoxia with/without Sildenafil | 4 hours | 
| Differences in cardiac output | Differences in cardiac output at rest and during exercise under normoxia/hypoxia with/without Sildenafil | 4 hours | 
| Differences in pulmonary vascular resistance | Differences in pulmonary vascular resistance at rest and during exercise under normoxia/hypoxia with/without Sildenafil | 4 hours | 
| Differences in pulmonary artery wedge pressure | Differences in pulmonary artery wedge pressure at rest and during exercise under normoxia/hypoxia with/without Sildenafil | 4 hours | 
| Differences in right atrial pressure | Differences in right atrial pressure at rest and during exercise under normoxia/hypoxia with/without Sildenafil | 4 hours | 
| Differences in mixed venous oxygen saturation | Differences in mixed venous oxygen saturation at rest and during exercise, under normoxia/hypoxia with/without Sildenafil | 4 hours | 
| Differences in heart rate | Differences in heart rate at rest and during exercise, under normoxia/hypoxia with/without Sildenafil | 4 hours | 
| Differences in blood pressure | Differences in blood pressure at rest and during exercise, under normoxia/hypoxia with/without Sildenafil | 4 hours | 
| Differences in oxygen saturation | Differences in oxygen saturation at rest and during exercise, under normoxia/hypoxia with/without Sildenafil | 4 hours | 
| Differences in arterial blood gases | Differences in arterial blood gases at rest and during exercise under normoxia/hypoxia with/without Sildenafil | 4 hours | 
| Differences in mixed venous blood gases | Differences in mixed venous blood gases at rest and during exercise under normoxia/hypoxia with/without Sildenafil | 4 hours | 
| Differences in cerebral tissue oxygenation | Differences in cerebral tissue oxygenation at rest and during exercise, with normoxia/hypoxia with/without Sildenafil | 4 hours | 
| Differences in muscle tissue oxygenation | Differences in muscle tissue oxygenation at rest and during exercise, with normoxia/hypoxia with/without Sildenafil | 4 hours | 
| Differences in symptoms (Borg dyspnoea) | Differences in symptoms (Borg dyspnoea) at rest and during exercise under normoxia/hypoxia with/without Sildenafil | 4 hours | 
| Differences in symptoms (Borg leg effort) | Differences in symptoms (Borg leg effort) at rest and during exercise under normoxia/hypoxia with/without Sildenafil | 4 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypoxia, exercise, Sildenafil