Chronic Clinical Effect of Acetazolamide

Study Overview
=================
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.

Official Title
-----------------
Chronic Clinical Effect of Acetazolamide in Pulmonary Hypertension

Conditions
-----------------
Hypertension, Pulmonary

Intervention / Treatment
-----------------
* Drug: Acetazolamide
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acetazolamide<br>Twice a day 250 mg acetazolamide for 5 weeks | Drug: Acetazolamide<br> <br> |
| Placebo Comparator: Placebo<br>Placebo capsule 250 mg (Mannitol) twice a day 5 weeks | Drug: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in 6 min walk distance | At the end of both periods (AZA and Placebo) | 5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference of Quality of Life (QoL) assessed by the physical subscale of the living with pulmonary hypertension questionnaire (MLHF) | At the end of both periods (AZA and Placebo) | 5 weeks | 
| Progressive maximal ramp cardiopulmonary exercise testing | At the end of both periods (AZA and Placebo) | 5 weeks | 
| cerebral and muscle tissue oxygenation | At the end of both periods (AZA and Placebo) at rest and exercise | 5 weeks | 
| daily activity | actigraphy | 5 weeks | 
| morphological and functional parameters of the heart | measured by echocardiography | 5 weeks | 
| New York Heart Association functional class | At the end of both periods (AZA and Placebo) | 5 weeks | 
| Short-form medical outcome questionnaire (SF-36) | At the end of both periods (AZA and Placebo) | 5 weeks | 
| Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) | At the end of both periods (AZA and Placebo) | 5 weeks | 
| N-terminal pro-brain natriuretic Peptide (NT-proBNP) | At the end of both periods (AZA and Placebo) | 5 weeks | 
| mean nocturnal oxygen Saturation during ambulatory sleep studies | At the end of both periods (AZA and Placebo) | 5 weeks | 
| apnea/hypopnea index during ambulatory sleep studies | At the end of both periods (AZA and Placebo) | 5 weeks | 
| Stroop test of cognitive performance | At the end of both periods (AZA and Placebo) | 5 weeks | 
| Trail making test (test of cognitive Performance) | At the end of both periods (AZA and Placebo) | 5 weeks | 
| 5 point test (test of cognitive Performance) | At the end of both periods (AZA and Placebo) | 5 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Treatment Outcome, Acetazolamide