Acute Hemodynamic Effect of Acetazolamide in Pulmonary Hypertension (AcuteAZA)

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

Study Overview

• Status: Completed
• Conditions: Hypertension, Pulmonary
• Intervention / Treatment: Drug: Placebo; Drug: Acetazolamide

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.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Switzerland
  • Zurich, Switzerland, 8091
    • University Hospital Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Zurich
• Investigators: Principal Investigator: Silvia Ulrich, MD, UniversityHospital Zurich

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): April 5, 2019
• Study Completion (Actual): April 5, 2019

Study Registration Dates

• First Submitted: March 24, 2016
• First Submitted That Met QC Criteria: April 25, 2016
• First Posted (Estimate): April 28, 2016

Study Record Updates

• Last Update Posted (Actual): August 13, 2019
• Last Update Submitted That Met QC Criteria: August 12, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Acetazolamide; Hemodynamics
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Carbonic Anhydrase Inhibitors; Natriuretic Agents; Diuretics; Anticonvulsants; Acetazolamide
• Other Study ID Numbers: KEK-ZH-2016-00089

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided