Clinical trial NCT02755259: Acute Hemodynamic Effect of Acetazolamide in Pulmonary Hypertension
Official title: Acute Hemodynamic Effect of Acetazolamide in Pulmonary Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Hypertension, Pulmonary
Keywords: Acetazolamide
Hemodynamics
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2016-04-28
Enrollment: 33
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Pulmonary vascular resistance (PVR) AZA vs. Placebo (rest)
timeFrame: 60 minutes
measure: PVR AZA vs. Placebo (exercise)
timeFrame: 60 minutes
measure: PVR AZA vs. Placebo (hypoxia)
timeFrame: 60 minutes
Secondary outcomes:
measure: partial pressure of the oxygen
timeFrame: 60 minutes
measure: Oxygen uptake
timeFrame: 15 minutes
measure: minute ventilation
timeFrame: 15 minutes
measure: arterial oxygenation
timeFrame: 60 minutes
measure: tissue oxygenation
timeFrame: 60 minutes
measure: mean pulmonary arterial pressure
timeFrame: 60 minutes
measure: cardiac output
timeFrame: 60 minutes
measure: cardiac index
timeFrame: 60 minutes
measure: pulmonary wedge pressure
timeFrame: 60 minutes
measure: Borg scale dyspnea and leg effort
timeFrame: 15 minutes
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: University Hospital Zurich
Study officials:
affiliation: UniversityHospital Zurich
name: Silvia Ulrich, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Duknic M, Lichtblau M, Saxer S, Berlier C, Schneider SR, Schwarz EI, Carta AF, Furian M, Bloch KE, Ulrich S. Comparison of Repetitive Cardiac Output Measurements at Rest and End-Exercise by Direct Fick Using Pulse Oximetry vs. Blood Gases in Patients With Pulmonary Hypertension. Front Med (Lausanne). 2021 Nov 23;8:776956. doi: 10.3389/fmed.2021.776956. eCollection 2021.