Hemodynamic Effects During Exercise in Patients With Pulmonary Hypertension Receiving Sildenafil (HEXASN)

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

To study hemodynamic effects of Sildenafil during exercise in patients with pulmonary hypertension.

Study Overview

• Status: Completed
• Conditions: Hypertension, Pulmonary
• Intervention / Treatment: Other: Hemodynamic effect of exercise under Sildenafil; Other: Hemodynamic effect of exercise

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Zurich, Switzerland, 8091
    • UniversityHospital Zurich, Department of Pulmonology
  • Zurich
    • Zürich, Zurich, Switzerland, 8091
      • University Hospital of Zürich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hemodynamic effect of exercise under Sildenafil; 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 under SIldenafil.	Other: Hemodynamic effect of exercise under Sildenafil; 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 under SIldenafil.
Other: Hemodynamic effect of exercise; 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: Hemodynamic effect of exercise; 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.

What is the study measuring?

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 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 with/without Sildenafil	4 hours
Differences in cardiac output	Differences in cardiac output at rest and during exercise under normoxia with/without Sildenafil	4 hours
Differences in pulmonary vascular resistance	Differences in pulmonary vascular resistance at rest and during exercise under normoxia with/without Sildenafil	4 hours
Differences in pulmonary artery wedge pressure	Differences in pulmonary artery wedge pressure at rest and during exercise under normoxia with/without Sildenafil	4 hours
Differences in right atrial pressure	Differences in right atrial pressure at rest and during exercise under normoxia with/without Sildenafil	4 hours
Differences in mixed venous oxygen saturation	Differences in mixed venous oxygen saturation at rest and during exercise under normoxia with/without Sildenafil	4 hours
Differences in heart rate	Differences in heart rate at rest and during exercise, under normoxia with/without Sildenafil	4 hours
Differences in blood pressure (systolic and diastolic)	Differences in blood pressure (systolic and diastolic) at rest and during exercise, under normoxia with/without Sildenafil	4 hours
Differences in oxygen saturation	Differences in oxygen saturation at rest and during exercise, under normoxia with/without Sildenafil	4 hours
Differences in arterial blood gases	Differences in arterial blood gases at rest and during exercise under normoxia with/without Sildenafil	4 hours
Differences in mixed venous blood gases	Differences in mixed venous blood gases at rest and during exercise under normoxia with/without Sildenafil	4 hours
Differences in cerebral tissue oxygenation	Differences in cerebral tissue oxygenation at rest and during exercise, under normoxia with/without Sildenafil	4 hours
Differences in muscle tissue oxygenation	Differences in muscle tissue oxygenation at rest and during exercise, under normoxia with/without Sildenafil	4 hours
Differences in symptoms (Borg dyspnoea)	Differences in symptoms (Borg dyspnoea, Borg CR10, scale 0-10) at rest and during exercise under normoxia with/without Sildenafil	4 hours
Differences in symptoms (leg effort)	Differences in symptoms (leg effort, scale 0-10, 10 is maximal exhaustion) at rest and during exercise under normoxia with/without Sildenafil	4 hours

Collaborators and Investigators

• Sponsor: University of Zurich
• Investigators: Principal Investigator: Silvia Ulrich, Prof. Dr., UniversityHospital Zurich, Department of Pulmonology

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Actual): May 31, 2023
• Study Completion (Actual): May 31, 2023

Study Registration Dates

• First Submitted: December 20, 2020
• First Submitted That Met QC Criteria: January 11, 2021
• First Posted (Actual): January 13, 2021

Study Record Updates

• Last Update Posted (Actual): June 6, 2023
• Last Update Submitted That Met QC Criteria: June 5, 2023
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: exercise; hemodynamics; hypoxia; Vasodilative drug
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate
• Other Study ID Numbers: 2020-02163_A2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will share individual participant data after publication of the manuscript. The decision about the platform is ongoing.
• IPD Sharing Time Frame: After publication of the manuscript.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No