MedPath

Chronic Clinical Effect of Acetazolamide

Phase 2
Completed
Conditions
Hypertension, Pulmonary
Interventions
Drug: Placebo
Registration Number
NCT02755298
Lead Sponsor
University of Zurich
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
24
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
AcetazolamideAcetazolamideTwice a day 250 mg acetazolamide for 5 weeks
PlaceboPlaceboPlacebo capsule 250 mg (Mannitol) twice a day 5 weeks
Primary Outcome Measures
NameTimeMethod
Difference in 6 min walk distance5 weeks

At the end of both periods (AZA and Placebo)

Secondary Outcome Measures
NameTimeMethod
daily activity5 weeks

actigraphy

Progressive maximal ramp cardiopulmonary exercise testing5 weeks

At the end of both periods (AZA and Placebo)

morphological and functional parameters of the heart5 weeks

measured by echocardiography

Trail making test (test of cognitive Performance)5 weeks

At the end of both periods (AZA and Placebo)

cerebral and muscle tissue oxygenation5 weeks

At the end of both periods (AZA and Placebo) at rest and exercise

New York Heart Association functional class5 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)

mean nocturnal oxygen Saturation during ambulatory sleep studies5 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)

Short-form medical outcome questionnaire (SF-36)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)

apnea/hypopnea index during ambulatory sleep studies5 weeks

At the end of both periods (AZA and Placebo)

Stroop test of cognitive performance5 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)

Trial Locations

Locations (1)

University Hospital Zurich

🇨🇭

Zurich, Switzerland

© Copyright 2025. All Rights Reserved by MedPath