Hypertension, Pulmonary
Conditions
Keywords
Treatment Outcome, Acetazolamide
Brief summary
The study seeks primarily to determine the chronic clinical effect of AZA on exercise capacity (6MWD) compared to placebo.
Detailed description
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. We 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 chronic clinical effects of AZA in PH patients.
Interventions
DRUGAcetazolamide
DRUGPlacebo
Sponsors
University of Zurich
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* All patients undergoing right heart catheterisation (RHC) for a clinical indication and who are diagnosed with precapillary PH (mean pulmonary arterial pressure (mPAP) ≥25 mmHg, pulmonary wedge pressure (PAWP) ≤15mmHg) * Patients have to be in a stable condition, on the same medication for \>4 weeks
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in 6 min walk distance | 5 weeks | At the end of both periods (AZA and Placebo) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progressive maximal ramp cardiopulmonary exercise testing | 5 weeks | At the end of both periods (AZA and Placebo) |
| cerebral and muscle tissue oxygenation | 5 weeks | At the end of both periods (AZA and Placebo) at rest and exercise |
| daily activity | 5 weeks | actigraphy |
| morphological and functional parameters of the heart | 5 weeks | measured by echocardiography |
| New York Heart Association functional class | 5 weeks | At the end of both periods (AZA and Placebo) |
| Short-form medical outcome questionnaire (SF-36) | 5 weeks | At the end of both periods (AZA and Placebo) |
| Difference of Quality of Life (QoL) assessed by the physical subscale of the living with pulmonary hypertension questionnaire (MLHF) | 5 weeks | At the end of both periods (AZA and Placebo) |
| N-terminal pro-brain natriuretic Peptide (NT-proBNP) | 5 weeks | At the end of both periods (AZA and Placebo) |
| mean nocturnal oxygen Saturation during ambulatory sleep studies | 5 weeks | At the end of both periods (AZA and Placebo) |
| apnea/hypopnea index during ambulatory sleep studies | 5 weeks | At the end of both periods (AZA and Placebo) |
| Stroop test of cognitive performance | 5 weeks | At the end of both periods (AZA and Placebo) |
| Trail making test (test of cognitive Performance) | 5 weeks | At the end of both periods (AZA and Placebo) |
| 5 point test (test of cognitive Performance) | 5 weeks | At the end of both periods (AZA and Placebo) |
| Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) | 5 weeks | At the end of both periods (AZA and Placebo) |
Countries
Switzerland
Outcome results
None listed