Acute Hemodynamic Effect of Acetazolamide in Pulmonary Hypertension

Study Overview
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Brief Summary
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To study the acute effect of acetazolamide (AZA) on pulmonary hemodynamics in patients with pulmonary hypertension (PH) undergoing clinically indicated right heart catheterisation (RHC).

Detailed Description
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Pulmonary hypertension (PH) of various etiologies causes dyspnea, impairs exercise performance and is associated with reduced quality of life (QoL) and survival. Treatment options include therapy for any underlying causes, pulmonary vasodilator drugs, oxygen and, in selected cases, pulmonary endarterectomy or lung transplantation. Unfortunately, PH specific drugs are expensive, associated with side effects and even combined pharmacological treatment is often not sufficient to achieve clinical benefits. Therefore, novel therapeutic drugs are needed. The investigators have recently demonstrated that sleep related breathing disorders, which are common in PH patients, can be improved by both nocturnal oxygen therapy and acetazolamide (AZA). AZA is a carbonic anhydrase (CA) inhibitor that acts as a respiratory stimulant thereby improving oxygenation and possibly PH. There are even data suggesting that CA-inhibitors have a direct pulmonary vasodilator effect. However, the potential role of AZA in the treatment of PH has not been conclusively studied. Therefore, the purpose of the current project is to investigate, the acute hemodynamic clinical effects of AZA in PH patients.

Official Title
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Acute Hemodynamic Effect of Acetazolamide in Pulmonary Hypertension

Conditions
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Hypertension, Pulmonary

Intervention / Treatment
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* Drug: Acetazolamide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients undergoing RHC for a clinical indication and who are diagnosed with precapillary PH (mPAP ≥25 mmHg, pulmonary wedge pressure (PAWP) ≤15mmHg) Exclusion Criteria: Patients in whom a RHC is clinically not indicated pregnant women PH in left heart disease or with more than mild chronic obstructive pulmonary disease or restrictive lung disease.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acetazolamide<br>Diamox 500mg i.v. (1x) | Drug: Acetazolamide<br> <br> |
| Placebo Comparator: Placebo<br>Placebo Saline injection (1x) | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary vascular resistance (PVR) AZA vs. Placebo (rest) | At the end of phase at rest | 60 minutes | 
| PVR AZA vs. Placebo (exercise) | At the end of phase at exercise | 60 minutes | 
| PVR AZA vs. Placebo (hypoxia) | At the end of phase under hypoxia | 60 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| partial pressure of the oxygen | At the end of each phase (rest, exercise and hypoxia) | 60 minutes | 
| Oxygen uptake |  | 15 minutes | 
| minute ventilation |  | 15 minutes | 
| arterial oxygenation | At the end of each phase (rest, exercise and hypoxia) | 60 minutes | 
| tissue oxygenation | At the end of each phase (rest, exercise and hypoxia) | 60 minutes | 
| mean pulmonary arterial pressure | At the end of each phase (rest, exercise and hypoxia) | 60 minutes | 
| cardiac output | At the end of each phase (rest, exercise and hypoxia) | 60 minutes | 
| cardiac index | At the end of each phase (rest, exercise and hypoxia) | 60 minutes | 
| pulmonary wedge pressure | At the end of each phase (rest, exercise and hypoxia) | 60 minutes | 
| Borg scale dyspnea and leg effort |  | 15 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acetazolamide, Hemodynamics